WO2021149465A1 - Processing device and measurement system - Google Patents

Processing device and measurement system Download PDF

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Publication number
WO2021149465A1
WO2021149465A1 PCT/JP2020/049204 JP2020049204W WO2021149465A1 WO 2021149465 A1 WO2021149465 A1 WO 2021149465A1 JP 2020049204 W JP2020049204 W JP 2020049204W WO 2021149465 A1 WO2021149465 A1 WO 2021149465A1
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WO
WIPO (PCT)
Prior art keywords
heat medium
temperature
processing apparatus
storage tank
sample solution
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Application number
PCT/JP2020/049204
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French (fr)
Japanese (ja)
Inventor
貴亮 森
崇裕 宮戸
Original Assignee
富士フイルム株式会社
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Application filed by 富士フイルム株式会社 filed Critical 富士フイルム株式会社
Priority to JP2021573038A priority Critical patent/JP7394885B2/en
Publication of WO2021149465A1 publication Critical patent/WO2021149465A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01LMEASURING FORCE, STRESS, TORQUE, WORK, MECHANICAL POWER, MECHANICAL EFFICIENCY, OR FLUID PRESSURE
    • G01L7/00Measuring the steady or quasi-steady pressure of a fluid or a fluent solid material by mechanical or fluid pressure-sensitive elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/579Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving limulus lysate
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor

Definitions

  • This disclosure relates to processing equipment and measurement systems.
  • a measurement using a lysate reagent containing a horseshoe crab blood cell extract is known.
  • the amount of endotoxin and the amount of ⁇ -glucan in the sample solution can be measured.
  • Endotoxin is a lipopolysaccharide that constitutes the cell wall of Gram-negative bacteria, and is a typical pyrogen that causes a biological reaction such as fever when it enters the blood even in a trace amount.
  • Specimens include biological samples such as blood, as well as pharmaceuticals (for example, injections) that are directly introduced into the living body.
  • Japanese Unexamined Patent Publication No. 2017-129249 describes a measuring device for measuring the amount of endotoxin in a sample solution using a LAL (Limulus Amebocyte Lysate) reagent as a lysate reagent. Further, Japanese Patent Application Laid-Open No. 08-029432 describes a processing apparatus for pretreating a sample solution.
  • LAL Limulus Amebocyte Lysate
  • the processing apparatus described in Japanese Patent Application Laid-Open No. 08-029432 includes a transport mechanism for transporting a sample container from a heating unit to a cooling unit by a handling robot.
  • a transport mechanism for transporting a sample container from a heating unit to a cooling unit by a handling robot.
  • the sample container inserted into the container insertion hole of the heating unit is grasped by the handling robot, and the arm of the robot is moved upward to pull out the sample container from the container insertion hole.
  • the handling robot conveys the sample container to the upper part of the cooling unit, and the arm of the robot is moved downward to insert the sample container into the container insertion hole of the cooling unit.
  • the technique of the present disclosure can suppress a transport defect when transporting the sample container from the heating section to the cooling section, and can suppress a long processing time due to the transport of the sample container. It is an object of the present invention to provide a possible processing device and a measurement system including the processing device.
  • the processing apparatus accommodates a sample container and can store a fluid heat medium for changing the temperature of the sample solution in the sample container around the sample container.
  • the accommodation tank is provided with a supply port for supplying a heat medium and a discharge port for discharging the heat medium, and the heat medium exchange mechanism is connected to the supply port and the discharge port.
  • the first heat medium or the second heat medium in the accommodating tank may be circulated through the pipes provided.
  • the processing apparatus of the above aspect it is connected to the first supply path connected to the first heat medium supply unit that supplies the first heat medium and the second heat medium supply unit that supplies the second heat medium.
  • a valve for switching between a second supply path, a first state for communicating the first supply path and the supply port, and a second state for communicating the second supply path and the supply port may be provided.
  • the heat medium supplied from the heat medium supply unit is supplied to the supply port, and the heat medium is placed on the supply path at the first temperature before being supplied to the supply port.
  • a first temperature adjusting unit that converts to a first heat medium by heating above, and a second heat medium that is arranged on a supply path and cools the heat medium to a second temperature or lower before being supplied to a supply port.
  • a second temperature adjusting unit for converting to may be provided.
  • the heat medium may be a liquid.
  • the heat medium exchange mechanism is controlled to control the second heat to the storage tank.
  • a control unit for supplying a medium may be provided.
  • the processing apparatus of the above aspect includes a heater that heats the heat medium to be the first heat medium, and the temperature of the heater may be 30 ° C. or higher and 80 ° C. or lower.
  • the temperature of the heater may be 60 ° C. or higher and 80 ° C. or lower.
  • the processing apparatus of the above aspect includes a cooling element for cooling in order to use the heat medium as the second heat medium, and the temperature of the cooling element may be 0 ° C. or higher and 10 ° C. or lower.
  • the storage tank may be configured to store a plurality of sample containers.
  • the sample solution is the measurement target of the measurement using the reagent containing the horseshoe crab blood cell extract, and the process of changing the temperature of the sample solution by the heat medium exchange mechanism executes the above measurement. It may be a pretreatment performed before the processing is performed.
  • the measurement system includes the above-mentioned processing device and a measuring device for measuring a sample solution.
  • an apparatus and a measurement system including the processing apparatus can be provided.
  • FIG. 1 is a diagram showing an outline of a measurement system 1 provided with a processing device 10 according to the first embodiment of the present disclosure.
  • the measuring system 1 includes a processing device 10 and a measuring device 60.
  • the processing apparatus 10 performs pretreatment performed before performing endotoxin measurement on the sample solution C produced by adding the buffer solution B to the sample A such as a biological sample and diluting it.
  • the measuring device 60 executes endotoxin measurement with the sample solution C after pretreatment as a measurement target.
  • endotoxin is a typical pyrogen that causes a biological reaction such as fever by entering the blood even in a small amount, and sample A is directly introduced into the living body in addition to a biological sample such as blood. Pharmaceuticals (eg, injections, etc.).
  • the amount of endotoxin in the sample solution C is measured, and the endotoxin in the sample A is quantified.
  • the endotoxin measurement is a measurement using a reagent such as lysate reagent D containing horseshoe crab blood cell extract.
  • Endotoxin measurement is a measurement utilizing the fact that endotoxin causes aggregation and coagulation of horseshoe crab blood cell extract.
  • lysate reagent D containing horseshoe crab blood cell extract is added to sample solution C.
  • the sample solution E is produced by stirring the sample solution C to which the lysate reagent D is added.
  • the amount of endotoxin in the sample solution E is measured based on the change in the characteristics of the sample solution E.
  • a lysate reagent prepared from a blood cell extract of Atlantic horseshoe crab is called a LAL (Limulus Amebocyte Lysate) reagent.
  • the measuring device 60 in the measuring system 1 of the present embodiment uses the LAL reagent as the lysate reagent D, and the ratio using the change in turbidity of the sample solution E in the process of gelation of the lysate reagent D by the reaction with endotoxin as an index. Endotoxin is measured by the turbidity method.
  • endotoxin measurement is performed by the turbidimetry method, pretreatment for heating and cooling the sample solution C is required prior to the measurement. As shown in FIG. 1, pretreatment is performed on the sample solution C, and endotoxin measurement is performed on the sample solution E containing the sample solution C and the lysate reagent D after the pretreatment.
  • a sample solution C produced by adding a buffer solution B to a sample A and diluting the sample solution C is about.
  • Heat treatment is performed to inactivate the interfering factors in endotoxin measurement by heating at a temperature of 70 ° C. for about 10 minutes.
  • the sample solution C at about 70 ° C. is cooled to a temperature of about 5 ° C. to perform a cooling treatment for stopping the inactivation treatment.
  • the time of the cooling process from the start of cooling to the end of cooling is, for example, about 3 minutes.
  • the cooling treatment if it takes time to cool the sample solution C at about 70 ° C to a temperature of about 5 ° C., the time for the inactivation treatment for the sample solution C varies, and the accuracy of endotoxin measurement decreases. Therefore, in the pretreatment, it is necessary to rapidly cool the sample solution C, specifically, to cool the sample solution C at about 70 ° C to a temperature of about 5 ° C. in a short time.
  • the processing device 10 in the measurement system 1 of the present embodiment is a device that performs the above pretreatment on the sample solution C diluted by adding the buffer solution B to the sample A.
  • FIG. 3 is a schematic view showing the configuration of the processing device 10.
  • the processing device 10 includes a storage tank 20, a heat medium exchange mechanism, and a control unit 11.
  • the storage tank 20 can house the sample container 5 and store the fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5.
  • the heat medium exchange mechanism exchanges the heat medium in the accommodating tank 20.
  • the control unit 11 controls the heat medium exchange mechanism.
  • the sample container 5 loaded in the processing device 10 has, for example, a cylindrical appearance, and includes a main body 5a and a lid 5b.
  • FIG. 4 is a perspective view of the storage tank 20.
  • FIG. 5 is an exploded perspective view of the storage tank 20.
  • FIG. 6 is a cross-sectional view of the storage tank 20 (VI-VI line cross-sectional view in FIG. 4).
  • the sample container 5 is not a cross-sectional view but a side view.
  • a plurality of container insertion holes 20b for inserting the sample container 5 are formed on the upper surface 20a of the storage tank 20.
  • a supply port 20d for supplying the heat medium 15 into the storage tank 20 is provided on one side surface 20c in the longitudinal direction.
  • a discharge port 20f for discharging the heat medium 15 from the inside of the storage tank 20 is provided on the other side surface 20e in the longitudinal direction.
  • the storage tank 20 includes a water tank type container body 21 having an open upper surface, a holding member 22 for holding the sample container 5, a lid 23 for sealing the opening of the container body 21, and piping attachment on the side of the supply port 20d.
  • a metal fitting 24 and a pipe mounting metal fitting 25 on the side of the discharge port 20f are provided.
  • a supply port 20d is formed on one side surface 21c in the longitudinal direction, and a discharge port 20f is formed on the other side surface 21e.
  • the container body 21 is made of polyphthalamide.
  • the container body 21 is preferably made of a resin material having high heat resistance and heat insulating properties, high chemical resistance to a heat medium, and a small heat capacity, such as polyphthalamide (PPA) or polyphenylene ether (PPE).
  • the holding member 22 has a shape in which a flat plate-shaped pedestal portion 22a and a plurality of tubular container insertion portions 22b provided on the pedestal portion 22a are integrally formed.
  • the holding member 22 is housed inside the container body 21.
  • the holding member 22 is made of aluminum.
  • the holding member 22 is preferably made of a metal material such as aluminum, which has excellent thermal conductivity, is resistant to rust, is inexpensive, and has high workability.
  • the lid 23 is formed with insertion ports 23a for a plurality of container insertion holes 20b.
  • the insertion port 23a of the lid 23 and the inside of the container insertion portion 22b of the holding member 22 communicate with each other to form the container insertion hole 20b.
  • the lid 23 is made of polyphthalamide, like the container body 21.
  • the lid 23 is preferably made of a resin material such as polyphthalamide (PPA) or polyphenylene ether (PPE), which has high heat resistance and heat insulating properties, high chemical resistance to a heat medium, and a small heat capacity. ..
  • the inner diameter of the container insertion hole 20b is formed to be slightly larger than the outer diameter of the sample container 5, but is substantially the same diameter. Therefore, when the sample container 5 is inserted into the container insertion hole 20b, the sample container 5 is held in the container insertion hole 20b without tilting.
  • 10 container insertion holes 20b are arranged side by side in a row.
  • the processing device 10 can be loaded with up to 10 sample containers 5 and can be pretreated at the same time.
  • the pipe mounting metal fitting 24 includes a metal fitting body 24a and a bolt 24b in which a pipe mounting portion and a bolt joint portion are formed.
  • the pipe mounting bracket 24 is formed by inserting the bolt coupling portion of the metal fitting body 24a into the supply port 20d from the outside of the container body 21 and connecting the bolt 24b to the metal fitting body 24a from the inside of the container body 21. It is attached to the container body 21.
  • the pipe mounting bracket 24 has a through hole, and when the pipe mounting bracket 24 is attached to the container body 21, the through hole of the pipe mounting bracket 24 functions as a supply port 20d (also in FIG. 6). reference).
  • the pipe mounting metal fitting 25 also includes a metal fitting body 25a and a bolt 25b in which a pipe mounting portion and a bolt joint portion are formed.
  • the pipe mounting bracket 25 is formed by inserting the bolt coupling portion of the metal fitting body 25a into the discharge port 20f from the outside of the container body 21 and connecting the bolt 25b to the metal fitting body 25a from the inside of the container body 21. It is attached to the container body 21.
  • the pipe mounting bracket 25 has a through hole, and when the pipe mounting bracket 25 is attached to the container body 21, the through hole of the pipe mounting bracket 25 functions as a discharge port 20f (also in FIG. 6). reference).
  • the heat medium exchange mechanism includes a first heat medium supply section 30, a first supply path 40, a first discharge path 44, a second heat medium supply section 31, a second supply path 41, and a second discharge path. It has 45.
  • the storage tank 20, the first heat medium supply unit 30, the first supply path 40, and the first discharge path 44 form a circulation path for the first heat medium 15a.
  • the first heat medium supply unit 30 supplies the first heat medium 15a to the accommodating tank 20 through the first supply path 40.
  • the first heat medium 15a heats the sample solution C stored in the sample container 5 in the storage tank 20 to the first temperature.
  • the first heat medium 15a supplied to the storage tank 20 is discharged from the storage tank 20 through the first discharge passage 44, and is collected in the first heat medium supply unit 30 through the first discharge passage 44.
  • the storage tank 20, the second heat medium supply unit 31, the second supply path 41, and the second discharge path 45 form a circulation path for the second heat medium 15b.
  • the second heat medium supply unit 31 supplies the second heat medium 15b to the accommodating tank 20 through the second supply path 41.
  • the second heat medium 15b cools the sample solution C stored in the sample container 5 in the storage tank 20 from the state heated to the first temperature to the second temperature.
  • the second heat medium 15b supplied to the storage tank 20 is discharged from the storage tank 20 through the second discharge passage 45, and is collected in the second heat medium supply unit 31 through the second discharge passage 45.
  • the first supply path 40 and the second supply path 41 are connected to the supply port 20d of the storage tank 20 via the valve 32 and the common supply path 42.
  • the valve 32 switches between a first state in which the first supply path 40 and the supply port 20d communicate with each other and a second state in which the second supply path 41 and the supply port 20d communicate with each other. In the first state, the first heat medium 15a is supplied to the storage tank 20, and in the second state, the second heat medium 15b is supplied to the storage tank 20.
  • the first discharge passage 44 and the second discharge passage 45 are connected to the discharge port 20f of the storage tank 20 via the valve 33 and the common discharge passage 43.
  • the valve 33 switches between a first state in which the first discharge path 44 and the discharge port 20f communicate with each other and a second state in which the second discharge path 45 and the discharge port 20f communicate with each other.
  • the first heat medium supply unit 30 includes a storage unit 30a for storing the heat medium 15a, a heater 30b for heating the heat medium 15 stored in the storage unit 30a as the first heat medium 15a, and a pump 30d.
  • a pipe 30c for connecting the discharge port of the storage unit 30a and the supply port of the pump 30d is provided.
  • the temperature of the heater 30b can be set to 30 ° C. or higher and 80 ° C. or lower.
  • the temperature of the heater 30b is more preferably 60 ° C. or higher and 80 ° C. or lower.
  • the temperature of the heater 30b is set to 70 ° C. (an example of the first temperature) based on the control from the control unit 11.
  • the first supply path 40 is composed of a pipe connecting the discharge port of the pump 30d and the connection port 32a of the valve 32.
  • the first discharge passage 44 is composed of a pipe connecting the connection port 33a of the valve 33 and the supply port of the first heat medium supply unit 30.
  • the second heat medium supply unit 31 includes a storage unit 31a for storing the heat medium 15, a cooling element 31b for cooling the heat medium 15 stored in the storage unit 31a to be the second heat medium 15b, and a pump 31d. And a pipe 31c for connecting the discharge port of the storage unit 31a and the supply port of the pump 31d.
  • the temperature of the cooling element 31b can be set to 0 ° C. or higher and 10 ° C. or lower.
  • the temperature of the cooling element 31b is set to 5 ° C. (an example of the second temperature) based on the control from the control unit 11.
  • a Perche element is used as the cooling element 31b.
  • the second supply path 41 is composed of a pipe connecting the discharge port of the pump 31d and the connection port 32b of the valve 32.
  • the second discharge passage 45 is composed of a pipe connecting the connection port 33b of the valve 33 and the supply port of the second heat medium supply unit 31.
  • the valve 32 is a three-way valve, and is a common supply path connecting the connection port 32a to which the first supply path 40 is connected, the connection port 32b to which the second supply path 41 is connected, and the valve 32 and the supply port 20d.
  • a connection port 32c to which the 42 is connected is provided.
  • the valve 32 can switch between a first state in which the first supply path 40 and the supply port 20d communicate with each other and a second state in which the second supply path 41 and the supply port 20d communicate with each other based on the control from the control unit 11. It is configured in. In the first state, the connection port 32a and the connection port 32c communicate with each other internally. In the second state, the connection port 32b and the connection port 32c communicate with each other internally.
  • the common supply path 42 is composed of a pipe connecting the connection port 32c and the supply port 20d.
  • the valve 33 is a three-way valve, and is a common discharge path that connects the connection port 33a to which the first discharge path 44 is connected, the connection port 33b to which the second discharge path 45 is connected, and the valve 33 and the discharge port 20f.
  • a connection port 33c to which the 43 is connected is provided.
  • the valve 33 can switch between a first state in which the first discharge path 44 and the discharge port 20f communicate with each other and a second state in which the second discharge path 45 and the discharge port 20f communicate with each other based on the control from the control unit 11. It is configured in. In the first state, the connection port 33a and the connection port 33c communicate with each other internally. In the second state, the connection port 33b and the connection port 33c communicate with each other internally.
  • the common discharge path 43 is composed of a pipe connecting the discharge port 20f and the connection port 33c.
  • the control unit 11 includes a CPU (Central Processing Unit) 11a, a memory 11b, and a storage 11c in which a control program is stored.
  • the memory 11b is a work memory used by the CPU 11a when executing a control program, and for example, a volatile memory is used.
  • the storage 11c is a non-volatile memory for storing various data, and a flash memory or the like is used.
  • the control unit 11 functions as a control unit that controls each unit of the heater 30b, the pump 30d, the cooling element 31b, the pump 31d, the valve 32, and the valve 33 by executing the control program.
  • FIG. 7 is a schematic view showing the configuration of the measuring device 60.
  • the measuring device 60 includes an LED (Light Emitting Diode) 61 that irradiates the sample container 5 with measurement light, and a PD (Photodiode) arranged at a position facing the LED 61 across the sample container 5. ) 62 and a measurement control unit 63.
  • the measurement control unit 63 measures the amount of endotoxin in the sample solution E based on the detection result of PD62. Further, the measurement control unit 63 controls the LED 61 and the PD 62.
  • the sample container 5 contains a sample solution E in which the pretreated sample solution C and the lysate reagent D are mixed.
  • the measurement control unit 63 includes a CPU (Central Processing Unit) 63a, a memory 63b, and a storage 63c in which a measurement control program is stored.
  • the memory 63b is a work memory used by the CPU 63a when executing a measurement control program, and for example, a volatile memory is used.
  • the storage 63c is a non-volatile memory for storing various data, and a flash memory or the like is used.
  • the measurement control unit 63 functions as a control unit that controls each unit of the LED 61 and the PD 62 by executing the measurement control program. Further, the measurement control unit 63 functions as a measurement unit that measures the amount of endotoxin in the sample solution E based on the detection result of PD62 by executing the measurement control program.
  • the turbidimetry method is a method using the change in turbidity in the process of gelation of lysate reagent D by the action of endotoxin as an index.
  • the turbidity of the sample solution E changes depending on the amount of endotoxin in the sample solution E and the elapsed time from the addition of the lysate reagent D to the sample solution C after the pretreatment.
  • the turbidity of the sample solution E changes, the amount of measurement light transmitted through the sample solution E changes.
  • the state and transition of the turbidity of the sample solution E are measured by measuring the change over time in the amount of transmitted light with the PD62. can do.
  • the measurement control unit 63 calculates the amount of endotoxin in the sample solution E based on the state and transition of the turbidity of the sample solution E.
  • FIG. 8 is a flowchart for explaining the flow of preprocessing in the processing apparatus 10.
  • sample solution C is produced by adding buffer solution B to sample A and diluting it.
  • the sample container 5 containing the generated sample solution C is inserted into the container insertion hole 20b of the storage tank 20.
  • the control unit 11 starts supplying the first heat medium 15a into the storage tank 20 and starts the circulation of the first heat medium 15a (step S1). Specifically, the control unit 11 controls the valve 32 to switch to the first state in which the first supply path 40 and the supply port 20d communicate with each other. Further, the valve 33 is controlled to switch to the first state in which the first discharge path 44 and the discharge port 20f communicate with each other.
  • the control unit 11 drives the pump 30d, and as shown by an arrow in FIG. 9, the first heat medium 15a in the first heat medium supply unit 30 is connected to the first supply path 40 and the first discharge path. Control is performed to circulate in the storage tank 20 through 44.
  • control unit 11 determines whether or not 10 minutes have passed since the circulation of the first heat medium 15a into the storage tank 20 was started (step S2). If it is determined in step S2 that 10 minutes have not passed (determination result No.), the control unit 11 continues to circulate the first heat medium 15a into the storage tank 20.
  • step S3 the control unit 11 controls the valve 32 to switch to the second state in which the second supply path 41 and the supply port 20d communicate with each other. Further, the valve 33 is controlled to switch to the second state in which the second discharge path 45 and the discharge port 20f communicate with each other.
  • the control unit 11 drives the pump 31d, and as shown by an arrow in FIG. 10, connects the second heat medium 15b in the second heat medium supply unit 31 to the second supply path 41 and the second discharge path. Control is performed to circulate in the storage tank 20 through 45.
  • control unit 11 determines whether or not 3 minutes have passed since the circulation of the second heat medium 15b into the storage tank 20 was started (step S4). When it is determined in step S4 that 3 minutes have not passed (determination result No.), the control unit 11 continues the circulation of the second heat medium 15b into the storage tank 20.
  • step S4 when it is determined that 3 minutes have passed (determination result Yes), the control unit 11 controls to stop the circulation of the second heat medium 15a into the accommodation tank 20 and ends the process.
  • the processing apparatus 10 of the present embodiment contains the sample container 5 and provides the sample container 5 with a fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5.
  • a heat medium exchange mechanism for exchanging a first heat medium 15a and a second heat medium 15b for cooling the sample solution C to a second temperature lower than the first temperature is provided.
  • both heating and cooling can be performed without moving the plurality of sample containers 5. Therefore, the processing time can be shortened as compared with the case where the sample containers are transported one by one by the handling robot as in the conventional processing apparatus.
  • the storage tank 20 is provided with a supply port 20d for supplying the heat medium 15 and a discharge port 20f for discharging the heat medium 15, and the heat medium exchange mechanism is provided.
  • the first heat medium 15a or the second heat medium 15b in the storage tank 20 is circulated through the pipes connected to the supply port 20d and the discharge port 20f.
  • the first heat medium 15a or the second heat medium 15b discharged from the storage tank 20 can be easily returned to the set temperature and supplied to the storage tank 20. It is easy to maintain the first heat medium 15a or the second heat medium 15b at a set temperature. Therefore, it is easier to heat or cool the heat medium 15a or the second heat medium 15b more quickly than in the case where the first heat medium 15a or the second heat medium 15b is not circulated.
  • the processing apparatus 10 of the present embodiment has a first supply path connected to a first heat medium supply unit 30 that supplies the first heat medium 15a, and a second heat medium supply unit that supplies the second heat medium 15b.
  • a second supply path connected to 31 and a valve 32 for switching between a first state for communicating the first supply path and the supply port 20d and a second state for communicating the second supply path and the supply port 20d are provided. ..
  • valve 32 By providing the valve 32 in this way, it is possible to distinguish between the supply paths of the first heat medium 15a and the second heat medium 16b having different temperatures.
  • the first heat medium supply unit 30 and the second heat medium supply unit 31 can be provided separately. Therefore, the first heat medium 15a and the second heat medium 15b are prepared separately, and one of them is selectively supplied into the storage tank 20, so that the first heat medium 15a or the second heat medium 15a or the second heat medium having a stable temperature can be selectively supplied.
  • the heat medium 15b can be supplied.
  • the heat medium 15 is harder to heat and cool when the specific heat is larger.
  • the heat medium 15 is more likely to heat the sample solution C using a heat medium 15 having a large specific heat (that is, difficult to cool) than to use a heat medium 15 having a relatively small specific heat (that is, easy to cool). Since the heat medium 15 is maintained in a heated state, the sample solution C can be heated quickly.
  • the heat medium 15 having a large specific heat that is, difficult to warm
  • the heat medium 15 is compared with the case where the heat medium 15 having a relatively small specific heat (that is, easy to warm) is used. Since the cooled state is maintained, the sample solution C can be cooled quickly.
  • pure water is used as the heat medium 15. Since pure water has few impurities and is hard to corrode, in addition to the above effects, it also contributes to the prevention of clogging of the piping of the heat medium exchange mechanism.
  • control for supplying the second heat medium 15b to the storage tank 20 by controlling the heat medium exchange mechanism after a preset set time has elapsed since the first heat medium 15a was supplied to the storage tank 20.
  • a heater 30b for heating the heat medium 15 as the first heat medium 15a is provided, and by setting the temperature of the heater 30b to 30 ° C. or higher and 80 ° C. or lower, pretreatment for endotoxin measurement by the turbidimetry method is performed. It is possible to carry out a heat treatment suitable for. By setting the temperature of the heater 30b to 60 ° C. or higher and 80 ° C. or lower, the heat treatment can be performed more efficiently.
  • a cooling element 31b for cooling the heat medium 15 as the second heat medium 15b is provided, and by setting the temperature of the cooling element 31b to 0 ° C. or higher and 10 ° C. or lower, endotoxin measurement by the turbidimetric method can be performed.
  • a cooling process suitable for the pretreatment can be performed.
  • the measurement system 1 can change the processing device 10 to the processing device 10B according to the second embodiment. Since the configurations other than the processing device 10B are the same as those in the first embodiment, the description other than the processing device 10B will be omitted.
  • FIG. 11 is a schematic view showing the configuration of the processing apparatus 10B according to the second embodiment.
  • the processing apparatus 10B accommodates the sample container 5 and can store the fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5.
  • the tank 20 includes a heat medium exchange mechanism for exchanging the heat medium in the accommodating tank 20, and a control unit 12 for controlling the heat medium exchange mechanism.
  • the storage tank 20 is the same as the processing device 10 according to the first embodiment, the description thereof will be omitted.
  • the heat medium exchange mechanism is arranged and supplied on the heat medium supply unit 34, the supply path 46 for supplying the heat medium 15 supplied from the heat medium supply unit 34 to the supply port 20d of the storage tank 20, and the supply path 46.
  • a first temperature adjusting unit 35 that converts the heat medium 15 into a first heat medium 15a by heating the heat medium 15 to a first temperature or higher before being supplied to the port 20d, and a first temperature adjusting unit 35 that is arranged on the supply path 46 and supplied to the supply port 20d.
  • a second temperature adjusting unit 36 that converts the heat medium 15 into a second heat medium 15b by cooling the heat medium 15 to a second temperature or lower, and a heat medium 15 discharged from the storage tank 20 are sent to the heat medium supply unit 34. It is provided with a discharge path 47 for returning.
  • the heat medium supply unit 34 includes a storage unit 34a for storing the heat medium 15, a pump 34c, and a pipe 34b for connecting the discharge port of the storage unit 34a and the supply port of the pump 34c.
  • the supply path 46 is composed of a pipe connecting the discharge port of the pump 34c and the supply port 20d of the storage tank 20.
  • the first temperature adjusting unit 35 is provided with a heater.
  • a pretreatment for the sample solution C when endotoxin measurement is performed by the turbidimetry method it is preferable to heat at 60 ° C. or higher and 80 ° C. or lower.
  • the temperature of the first heat medium 15a is 70 ° C.
  • the temperature of the heater is set so that the temperature of the heat medium 15 passing through the mounting position of the first temperature adjusting unit 35 of the supply path 46 is 70 ° C.
  • the second temperature adjusting unit 36 includes a Perche element which is a cooling element.
  • a Perche element which is a cooling element.
  • the temperature of the second heat medium 15b is set to 5 ° C.
  • the temperature of the cooling element is set so that the temperature of the heat medium 15 passing through the mounting position of the second temperature adjusting unit 36 of the supply path 46 is 5 ° C.
  • the discharge path 47 is composed of a pipe connecting the discharge port 20f of the storage tank 20 and the supply port of the storage unit 34a.
  • FIG. 12 is a cross-sectional view showing the peripheral structures of the first temperature adjusting unit 35 and the second temperature adjusting unit 36.
  • the first temperature adjusting unit 35 is attached so as to be in close contact with the supply path 46, and the heat medium 15 passing through the attachment position of the first temperature adjusting unit 35 in the supply path 46 is instantaneously passed. Is converted into the first heat medium 15a.
  • the cross-sectional shape of the supply path 46 is, for example, a flat shape having a thin thickness in the direction parallel to the paper surface and a long depth in the direction orthogonal to the paper surface with respect to the thickness.
  • the first temperature adjusting unit 35 extends in the depth direction of the supply path 46 so that the contact area with the supply path 46 becomes large. Therefore, since the amount of the heat medium 15 per unit time passing through the mounting position of the first temperature adjusting unit 35 is small, the heat medium 15 can be heated instantaneously.
  • the second temperature adjusting unit 36 also instantly converts the heat medium 15 passing through the mounting position of the second temperature adjusting unit 36 in the supply path 46 into the second heat medium 15b, similarly to the first temperature adjusting unit 35. ..
  • the second temperature adjusting unit 36 is also attached so as to be in close contact with the supply path 46, and is oriented in the depth direction of the supply path 46 so that the contact area with the supply path 46 becomes large. It is extending. As a result, since the amount of the heat medium 15 per unit time passing through the mounting position of the second temperature adjusting unit 36 is small, the heat medium 15 can be cooled instantly.
  • control unit 12 includes a CPU (Central Processing Unit) 12a, a memory 12b, and a storage 12c in which a control program is stored.
  • the control unit 12 functions as a control unit that controls each unit of the pump 34c, the first temperature adjustment unit 35, and the second temperature adjustment unit 36 by executing the control program.
  • FIG. 8 (common to the first embodiment) is a flowchart for explaining the flow of preprocessing in the processing apparatus 10B.
  • the control unit 12 sets the first heat medium. 15a is circulated in the storage tank 20 (step S1). Specifically, the control unit 12 drives the pump 34c and the first temperature adjusting unit 35 to convert the heat medium 15 passing through the supply path 46 into the first heat medium 15a, which is indicated by an arrow in FIG. As described above, the control is performed so that the first heat medium 15a is circulated in the storage tank 20.
  • control unit 12 determines whether 10 minutes have passed since the circulation of the first heat medium 15a into the storage tank 20 was started (step S2). If it is determined in step S2 that 10 minutes have not passed (determination result No.), the control unit 12 continues to circulate the first heat medium 15a into the storage tank 20.
  • step S2 When it is determined in step S2 that 10 minutes have passed (determination result Yes), the control unit 12 stops the circulation of the first heat medium 15a into the storage tank 20 and puts the second heat medium 15b in the storage tank. Circulate within 20 (step S3). Specifically, the control unit 12 stops driving the first temperature adjusting unit 35 and drives the second temperature adjusting unit 36 while driving the pump 34c to drive the heat medium 15 passing through the supply path 46. It is converted into a second heat medium 15b, and as shown by an arrow in FIG. 11, the second heat medium 15b is controlled to be circulated in the storage tank 20.
  • control unit 12 determines whether 3 minutes have passed since the circulation of the second heat medium 15b into the storage tank 20 was started (step S4). If it is determined in step S4 that 3 minutes have not passed (determination result No.), the control unit 12 continues to circulate the second heat medium 15b into the storage tank 20.
  • step S4 when it is determined that 3 minutes have passed (determination result Yes), the control unit 12 controls to stop the circulation of the second heat medium 15a into the storage tank 20 and ends the process.
  • the processing device 10B of the present embodiment can solve the problem of poor transport of the sample container and can shorten the processing time.
  • the processing apparatus 10B of the present embodiment is arranged on the supply path 46 and the supply path 46 for supplying the heat medium 15 supplied from the heat medium supply unit 34 to the supply port 20d.
  • a first temperature adjusting unit 35 that converts the heat medium 15 into a first heat medium 15a by heating the heat medium 15 to a first temperature or higher before being supplied to the supply port 20d, and a first temperature adjusting unit 35 arranged on the supply path 46 and connected to the supply port 20d.
  • a second temperature adjusting unit 36 that converts the heat medium 15 into a second heat medium 15b by cooling the heat medium 15 to a second temperature or lower before being supplied is provided.
  • the lysate reagent used for endotoxin measurement is not limited to the LAL reagent, and a TAL (Tachypleus Amebocyte Lysate) reagent prepared from a blood cell extract of a horseshoe crab (Tachypleus tridentatus), which is a different species from the American horseshoe crab, may be used.
  • TAL Techypleus Amebocyte Lysate
  • the endotoxin test method is not limited to the turbidimetry method described in the above embodiment, but is a gelation method using the gel formation of a lysate reagent by the action of endotoxin as an index, or a color development by hydrolysis of a synthetic substrate as an index. You may use the colorimetric method.
  • the measurement using the reagent containing the horseshoe crab blood cell extract is not limited to endotoxin, but may be ⁇ -glucan.
  • a processing apparatus that performs pretreatment for measurement using a reagent containing horseshoe crab blood cell extract has been described as an example, but it is applied to a processing apparatus that performs pretreatment for measurement using other reagents. You may.
  • the pretreatment for the sample solution is not limited to the treatment for heating for 10 minutes and then cooling for 3 minutes as described in the above embodiment, and may be appropriately changed according to the measurement performed on the sample solution.
  • the temperature adjustment process for the sample solution performed by the processing device is not limited to the pretreatment performed prior to the measurement, and may be used for any purpose.
  • the heat medium is not limited to pure water, and antifreeze may be used.
  • an antifreeze solution is used as the heat medium, the heat medium can be circulated in the heat medium exchange mechanism without freezing even at a temperature close to 0 ° C., so that the sample solution can be cooled more quickly.
  • the heat medium is not limited to a liquid, and any fluid may be used.
  • the hardware structure of the processing unit (Processing Unit) that executes various processes such as the control units 11 and 12 and the measurement control unit 63 includes various processors (Processors) shown below. ) Can be used.
  • processors in addition to the CPU (Central Processing Unit), which is a general-purpose processor that executes software and functions as various processing units, the circuit configuration can be changed after the manufacture of FPGA (Field Programmable Gate Array), etc.
  • FPGA Field Programmable Gate Array
  • a dedicated electric circuit that is a processor having a circuit configuration specially designed to execute a specific process such as a programmable logic device (PLD) and / or an ASIC (Application Specific Integrated Circuit). Etc. are included.
  • One processor may be composed of one of these various processors, or a combination of two or more processors of the same type or different types (for example, a combination of a plurality of FPGAs and / or a CPU and a CPU). It may be configured in combination with FPGA).
  • the various processing units are configured by using one or more of the above-mentioned various processors as a hardware structure.
  • an electric circuit in which circuit elements such as semiconductor elements are combined can be used.

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Abstract

This processing device is provided with: a housing tank that houses therein a sample container and that can store, around the sample container, a fluid-state heat medium for changing the temperature of a sample solution in the sample container; and a heat medium replacement mechanism that is for replacing a heat medium in the housing tank and that is for exchanging a first heat medium for heating the sample solution in the sample container to a first temperature with a second heat medium for cooling the sample solution to a second temperature lower than the first temperature.

Description

処理装置および測定システムProcessing equipment and measurement system
 本開示は、処理装置および測定システムに関する。 This disclosure relates to processing equipment and measurement systems.
 生体試料などの検体を分析するために、検体に含まれる種々の物質を測定することが行われている。このような測定として、カブトガニ血球抽出物を含むライセート試薬を用いた測定が知られている。ライセート試薬を用いることにより、検体溶液中のエンドトキシン量およびβ-グルカン量の測定を行うことができる。エンドトキシンは、グラム陰性菌の細胞壁を構成するリポ多糖であり、微量でも血中に入ることで、発熱などの生体反応を引き起こす代表的な発熱物質である。検体は、血液などの生体試料の他、生体内に直接導入される医薬品(例えば、注射剤など)などがある。このようなライセート試薬を用いた測定を行う際には、測定に先立って、検体溶液を加熱した後、検体溶液を冷却するといった前処理を行う場合があり、こうした前処理を行う処理装置が知られている。 In order to analyze a sample such as a biological sample, various substances contained in the sample are measured. As such a measurement, a measurement using a lysate reagent containing a horseshoe crab blood cell extract is known. By using the lysate reagent, the amount of endotoxin and the amount of β-glucan in the sample solution can be measured. Endotoxin is a lipopolysaccharide that constitutes the cell wall of Gram-negative bacteria, and is a typical pyrogen that causes a biological reaction such as fever when it enters the blood even in a trace amount. Specimens include biological samples such as blood, as well as pharmaceuticals (for example, injections) that are directly introduced into the living body. When performing a measurement using such a lysate reagent, a pretreatment such as heating the sample solution and then cooling the sample solution may be performed prior to the measurement, and a processing device that performs such pretreatment is known. Has been done.
 特開平2017-129429号公報には、ライセート試薬としてLAL(Limulus Amebocyte Lysate)試薬を用いて、検体溶液中のエンドトキシン量の測定を行う測定装置が記載されている。また、特開平08-029432号公報には、検体溶液に対して前処理を行う処理装置が記載されている。 Japanese Unexamined Patent Publication No. 2017-129249 describes a measuring device for measuring the amount of endotoxin in a sample solution using a LAL (Limulus Amebocyte Lysate) reagent as a lysate reagent. Further, Japanese Patent Application Laid-Open No. 08-029432 describes a processing apparatus for pretreating a sample solution.
 特開平08-029432号公報に記載の処理装置は、ハンドリングロボットによって検体容器を加熱部から冷却部に搬送する搬送機構を備えている。この搬送機構は、加熱部の容器挿入孔に挿入された検体容器をハンドリングロボットによって把持し、ロボットのアームを上方に移動させて容器挿入孔から検体容器を引き抜く。次に、ハンドリングロボットによって冷却部の上部まで検体容器を搬送し、ロボットのアームを下方に移動させて冷却部の容器挿入孔に検体容器を挿入する。 The processing apparatus described in Japanese Patent Application Laid-Open No. 08-029432 includes a transport mechanism for transporting a sample container from a heating unit to a cooling unit by a handling robot. In this transport mechanism, the sample container inserted into the container insertion hole of the heating unit is grasped by the handling robot, and the arm of the robot is moved upward to pull out the sample container from the container insertion hole. Next, the handling robot conveys the sample container to the upper part of the cooling unit, and the arm of the robot is moved downward to insert the sample container into the container insertion hole of the cooling unit.
 しかしながら、特開平08-029432号公報の搬送機構のように、ハンドリングロボットによって検体容器を搬送する場合、搬送中にハンドリングロボットによって把持された検体容器が傾いて、冷却部の容器挿入孔に挿入できなくなるといった搬送不良が生じるおそれがある。また、ハンドリングロボットによって検体容器を1個ずつ搬送する場合、検体容器の数が多いと搬送効率が悪く、処理時間が長時間化するという問題がある。 However, when the sample container is transported by the handling robot as in the transport mechanism of Japanese Patent Application Laid-Open No. 08-029432, the sample container gripped by the handling robot is tilted during the transport and can be inserted into the container insertion hole of the cooling unit. There is a risk of transport defects such as disappearance. Further, when the sample containers are transported one by one by the handling robot, there is a problem that if the number of sample containers is large, the transport efficiency is poor and the processing time becomes long.
 上記事情に鑑み、本開示の技術は、検体容器を加熱部から冷却部に搬送する際の搬送不良を抑制し、かつ、検体容器の搬送に起因する処理時間の長時間化を抑制することが可能な処理装置およびこの処理装置を備えた測定システムを提供することを目的とする。 In view of the above circumstances, the technique of the present disclosure can suppress a transport defect when transporting the sample container from the heating section to the cooling section, and can suppress a long processing time due to the transport of the sample container. It is an object of the present invention to provide a possible processing device and a measurement system including the processing device.
 本開示の一態様に係る処理装置は、検体容器を収容し、かつ、検体容器内の検体溶液の温度を変化させるための流体状の熱媒体を検体容器の周囲に貯留することが可能な収容槽と、収容槽内の熱媒体を交換する熱媒体交換機構であって、検体容器内の検体溶液を第1温度に加熱するための第1熱媒体と、第1温度よりも低い第2温度に検体溶液を冷却するための第2熱媒体とを交換する熱媒体交換機構と、を備える。 The processing apparatus according to one aspect of the present disclosure accommodates a sample container and can store a fluid heat medium for changing the temperature of the sample solution in the sample container around the sample container. A heat medium exchange mechanism for exchanging the heat medium in the tank and the storage tank, the first heat medium for heating the sample solution in the sample container to the first temperature, and the second temperature lower than the first temperature. Is provided with a heat medium exchange mechanism for exchanging a second heat medium for cooling the sample solution.
 上記態様の処理装置においては、収容槽には、熱媒体を供給する供給口と、熱媒体を排出する排出口とが設けられており、熱媒体交換機構は、供給口と排出口とに接続された配管を通じて、収容槽内の第1熱媒体または第2熱媒体を循環させてもよい。 In the processing apparatus of the above aspect, the accommodation tank is provided with a supply port for supplying a heat medium and a discharge port for discharging the heat medium, and the heat medium exchange mechanism is connected to the supply port and the discharge port. The first heat medium or the second heat medium in the accommodating tank may be circulated through the pipes provided.
 また、上記態様の処理装置においては、第1熱媒体を供給する第1熱媒体供給部に接続される第1供給路と、第2熱媒体を供給する第2熱媒体供給部に接続される第2供給路と、第1供給路と供給口を連通させる第1状態と、第2供給路と供給口を連通させる第2状態とを切り替える弁と、を備えてもよい。 Further, in the processing apparatus of the above aspect, it is connected to the first supply path connected to the first heat medium supply unit that supplies the first heat medium and the second heat medium supply unit that supplies the second heat medium. A valve for switching between a second supply path, a first state for communicating the first supply path and the supply port, and a second state for communicating the second supply path and the supply port may be provided.
 また、上記態様の処理装置においては、熱媒体供給部から供給される熱媒体を供給口に供給する供給路と、供給路上に配置され、供給口に供給される前に熱媒体を第1温度以上に加熱することにより第1熱媒体に変換する第1温度調整部と、供給路上に配置され、供給口に供給される前に熱媒体を第2温度以下に冷却することにより第2熱媒体に変換する第2温度調整部と、を備えてもよい。 Further, in the processing apparatus of the above aspect, the heat medium supplied from the heat medium supply unit is supplied to the supply port, and the heat medium is placed on the supply path at the first temperature before being supplied to the supply port. A first temperature adjusting unit that converts to a first heat medium by heating above, and a second heat medium that is arranged on a supply path and cools the heat medium to a second temperature or lower before being supplied to a supply port. A second temperature adjusting unit for converting to may be provided.
 また、上記態様の処理装置においては、熱媒体は、液体であってもよい。 Further, in the processing apparatus of the above aspect, the heat medium may be a liquid.
 また、上記態様の処理装置においては、収容槽に第1熱媒体が供給されてから予め設定された設定時間が経過した後、前記熱媒体交換機構を制御することにより、収容槽に第2熱媒体を供給させる制御部を備えてもよい。 Further, in the processing apparatus of the above aspect, after a preset set time has elapsed since the first heat medium was supplied to the storage tank, the heat medium exchange mechanism is controlled to control the second heat to the storage tank. A control unit for supplying a medium may be provided.
 また、上記態様の処理装置においては、熱媒体を第1熱媒体とするために加熱するヒーターを備え、ヒーターの温度は、30℃以上80℃以下であってもよい。なお、ヒーターの温度は、60℃以上80℃以下であってもよい。 Further, the processing apparatus of the above aspect includes a heater that heats the heat medium to be the first heat medium, and the temperature of the heater may be 30 ° C. or higher and 80 ° C. or lower. The temperature of the heater may be 60 ° C. or higher and 80 ° C. or lower.
 また、上記態様の処理装置においては、熱媒体を第2熱媒体とするために冷却する冷却素子を備え、冷却素子の温度は、0℃以上10℃以下であってもよい。 Further, the processing apparatus of the above aspect includes a cooling element for cooling in order to use the heat medium as the second heat medium, and the temperature of the cooling element may be 0 ° C. or higher and 10 ° C. or lower.
 また、上記態様の処理装置においては、収容槽は、複数の検体容器を収容する構成とされていてもよい。 Further, in the processing apparatus of the above aspect, the storage tank may be configured to store a plurality of sample containers.
 また、上記態様の処理装置においては、検体溶液は、カブトガニ血球抽出物を含む試薬を用いた測定の測定対象であり、熱媒体交換機構によって検体溶液の温度を変化させる処理は、上記測定を実行する前に行われる前処理であってもよい。 Further, in the processing apparatus of the above aspect, the sample solution is the measurement target of the measurement using the reagent containing the horseshoe crab blood cell extract, and the process of changing the temperature of the sample solution by the heat medium exchange mechanism executes the above measurement. It may be a pretreatment performed before the processing is performed.
 本開示の一態様に係る測定システムは、上記処理装置と、検体溶液に対する測定を行う測定装置と、を備える。 The measurement system according to one aspect of the present disclosure includes the above-mentioned processing device and a measuring device for measuring a sample solution.
 本開示の技術によれば、検体容器を加熱部から冷却部に搬送する際の搬送不良を抑制し、かつ、検体容器の搬送に起因する処理時間の長時間化を抑制することが可能な処理装置およびこの処理装置を備えた測定システムを提供することができる。 According to the technique of the present disclosure, it is possible to suppress a transfer defect when the sample container is transported from the heating unit to the cooling unit, and to suppress a long processing time due to the transportation of the sample container. An apparatus and a measurement system including the processing apparatus can be provided.
測定システムの概要を示す図である。It is a figure which shows the outline of the measurement system. 前処理における検体溶液の温度変化の推移を示すグラフである。It is a graph which shows the transition of the temperature change of the sample solution in the pretreatment. 第1実施形態に係る処理装置の構成を示す概略図である。It is the schematic which shows the structure of the processing apparatus which concerns on 1st Embodiment. 収容槽の斜視図である。It is a perspective view of a containment tank. 収容槽の分解斜視図である。It is an exploded perspective view of the containment tank. 収容槽の断面図である。It is sectional drawing of the containment tank. 測定装置の構成を示す概略図である。It is the schematic which shows the structure of the measuring device. 処理装置における前処理の流れを説明するためのフローチャートである。It is a flowchart for demonstrating the flow of the pre-processing in a processing apparatus. 処理装置における加熱時の状態を示す図である。It is a figure which shows the state at the time of heating in a processing apparatus. 処理装置における冷却時の状態を示す図である。It is a figure which shows the state at the time of cooling in a processing apparatus. 第2実施形態に係る処理装置の構成を示す概略図である。It is the schematic which shows the structure of the processing apparatus which concerns on 2nd Embodiment. 第1温度調整部および第2温度調整部の周辺の構造を示す断面図である。It is sectional drawing which shows the structure around the 1st temperature adjustment part and the 2nd temperature adjustment part.
「第1実施形態」
[測定システムの全体構成]
 図1は、本開示の第1実施形態に係る処理装置10を備えた測定システム1の概要を示す図である。図1に示すように、測定システム1は、処理装置10と、測定装置60とを備えている。処理装置10は、生体試料などの検体Aに緩衝液Bを加えて希釈することにより生成した検体溶液Cに対して、エンドトキシン測定を実行する前に行われる前処理を行う。測定装置60は、前処理後の検体溶液Cを測定対象として、エンドトキシン測定を実行する。
"First embodiment"
[Overall configuration of measurement system]
FIG. 1 is a diagram showing an outline of a measurement system 1 provided with a processing device 10 according to the first embodiment of the present disclosure. As shown in FIG. 1, the measuring system 1 includes a processing device 10 and a measuring device 60. The processing apparatus 10 performs pretreatment performed before performing endotoxin measurement on the sample solution C produced by adding the buffer solution B to the sample A such as a biological sample and diluting it. The measuring device 60 executes endotoxin measurement with the sample solution C after pretreatment as a measurement target.
 上述したとおり、エンドトキシンは、微量でも血中に入ることで、発熱などの生体反応を引き起こす代表的な発熱物質であり、検体Aは、血液などの生体試料の他、生体内に直接導入される医薬品(例えば、注射剤など)などである。エンドトキシン測定では、検体溶液C中のエンドトキシン量が測定され、検体A中のエンドトキシンの定量化が行われる。エンドトキシン測定は、カブトガニ血球抽出物を含むライセート試薬Dなどの試薬を用いた測定である。エンドトキシン測定は、エンドトキシンによりカブトガニ血球抽出物の凝集および凝固が起こることを利用した測定である。エンドトキシン測定では、先ず、カブトガニ血球抽出物を含むライセート試薬Dが検体溶液Cに添加される。ライセート試薬Dが添加された検体溶液Cが攪拌されることにより、検体溶液Eが生成される。次に、検体溶液Eの特性の変化に基づいて、検体溶液E中のエンドトキシン量が測定される。 As described above, endotoxin is a typical pyrogen that causes a biological reaction such as fever by entering the blood even in a small amount, and sample A is directly introduced into the living body in addition to a biological sample such as blood. Pharmaceuticals (eg, injections, etc.). In the endotoxin measurement, the amount of endotoxin in the sample solution C is measured, and the endotoxin in the sample A is quantified. The endotoxin measurement is a measurement using a reagent such as lysate reagent D containing horseshoe crab blood cell extract. Endotoxin measurement is a measurement utilizing the fact that endotoxin causes aggregation and coagulation of horseshoe crab blood cell extract. In endotoxin measurement, first, lysate reagent D containing horseshoe crab blood cell extract is added to sample solution C. The sample solution E is produced by stirring the sample solution C to which the lysate reagent D is added. Next, the amount of endotoxin in the sample solution E is measured based on the change in the characteristics of the sample solution E.
 ライセート試薬Dの原料となるカブトガニとして、アメリカカブトガニ(Limulus polyphemus)の血球抽出物から調製されるライセート試薬は、LAL(Limulus Amebocyte Lysate)試薬と呼ばれる。 As a horseshoe crab that is a raw material of lysate reagent D, a lysate reagent prepared from a blood cell extract of Atlantic horseshoe crab (Limulus polyphemus) is called a LAL (Limulus Amebocyte Lysate) reagent.
 本実施形態の測定システム1における測定装置60は、ライセート試薬DとしてLAL試薬を使用し、エンドトキシンとの反応によりライセート試薬Dがゲル化する過程での検体溶液Eの濁度変化を指標とする比濁法によりエンドトキシン測定を行う。比濁法によりエンドトキシン測定を行う場合、測定に先立って検体溶液Cに対して加熱および冷却を行う前処理が必要である。図1に示すとおり、検体溶液Cに対して前処理が行われ、前処理後の検体溶液Cとライセート試薬Dとを含む検体溶液Eに対してエンドトキシン測定が行われる。 The measuring device 60 in the measuring system 1 of the present embodiment uses the LAL reagent as the lysate reagent D, and the ratio using the change in turbidity of the sample solution E in the process of gelation of the lysate reagent D by the reaction with endotoxin as an index. Endotoxin is measured by the turbidity method. When endotoxin measurement is performed by the turbidimetry method, pretreatment for heating and cooling the sample solution C is required prior to the measurement. As shown in FIG. 1, pretreatment is performed on the sample solution C, and endotoxin measurement is performed on the sample solution E containing the sample solution C and the lysate reagent D after the pretreatment.
 比濁法によりエンドトキシン測定を行う場合の前処理は、具体的には、図2のグラフに示すように、先ず、検体Aに緩衝液Bを加えて希釈することにより生成した検体溶液Cを約70℃の温度で約10分間加熱することにより、エンドトキシン測定における干渉因子を不活化する加熱処理を行う。その後、約70°の検体溶液Cを約5℃の温度まで冷却することにより、不活化処理を停止する冷却処理を行う。冷却開始から冷却終了までの冷却処理の時間は例えば約3分間である。冷却処理において、約70°の検体溶液Cを約5℃の温度まで冷却するのに時間がかかると、検体溶液Cに対する不活化処理の時間にバラツキが生じて、エンドトキシン測定の精度が低下する。そのため、前処理において、検体溶液Cの冷却は急激に、具体的には、約70°の検体溶液Cを約5℃の温度まで冷却する時間を短時間で行う必要がある。 Specifically, as a pretreatment when endotoxin measurement is performed by the turbidimetry method, as shown in the graph of FIG. 2, first, a sample solution C produced by adding a buffer solution B to a sample A and diluting the sample solution C is about. Heat treatment is performed to inactivate the interfering factors in endotoxin measurement by heating at a temperature of 70 ° C. for about 10 minutes. Then, the sample solution C at about 70 ° C. is cooled to a temperature of about 5 ° C. to perform a cooling treatment for stopping the inactivation treatment. The time of the cooling process from the start of cooling to the end of cooling is, for example, about 3 minutes. In the cooling treatment, if it takes time to cool the sample solution C at about 70 ° C to a temperature of about 5 ° C., the time for the inactivation treatment for the sample solution C varies, and the accuracy of endotoxin measurement decreases. Therefore, in the pretreatment, it is necessary to rapidly cool the sample solution C, specifically, to cool the sample solution C at about 70 ° C to a temperature of about 5 ° C. in a short time.
 本実施形態の測定システム1における処理装置10は、検体Aに緩衝液Bを加えて希釈した検体溶液Cに対し、上記前処理を行う装置である。 The processing device 10 in the measurement system 1 of the present embodiment is a device that performs the above pretreatment on the sample solution C diluted by adding the buffer solution B to the sample A.
<処理装置>
 図3は、処理装置10の構成を示す概略図である。図3に示すように、処理装置10は、収容槽20と、熱媒体交換機構と、制御部11とを備える。収容槽20は、検体容器5を収容し、かつ、検体容器5内の検体溶液Cの温度を変化させるための流体状の熱媒体15を貯留することが可能である。熱媒体交換機構は、収容槽20内の熱媒体を交換する。制御部11は、熱媒体交換機構を制御する。処理装置10に装填される検体容器5は、例えば、外観が円筒形状であり、本体5aと蓋体5bとを備えている。収容槽20に貯留する流体状の熱媒体15としては、例えば純水が用いられる。
<Processing device>
FIG. 3 is a schematic view showing the configuration of the processing device 10. As shown in FIG. 3, the processing device 10 includes a storage tank 20, a heat medium exchange mechanism, and a control unit 11. The storage tank 20 can house the sample container 5 and store the fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5. The heat medium exchange mechanism exchanges the heat medium in the accommodating tank 20. The control unit 11 controls the heat medium exchange mechanism. The sample container 5 loaded in the processing device 10 has, for example, a cylindrical appearance, and includes a main body 5a and a lid 5b. As the fluid heat medium 15 stored in the storage tank 20, for example, pure water is used.
 図4は、収容槽20の斜視図である。図5は、収容槽20の分解斜視図である。図6は、収容槽20の断面図(図4中のVI-VI線断面図)である。なお、図6において、検体容器5は、断面図ではなく、側面図を示している。図4に示すように、収容槽20の上面20aには、検体容器5を挿入するための複数の容器挿入孔20bが形成されている。また、図5に示すように、収容槽20において、長手方向の一方の側面20cには、収容槽20内に熱媒体15を供給する供給口20dが設けられている。収容槽20において、長手方向の他方の側面20eには、収容槽20内から熱媒体15を排出する排出口20fが設けられている。 FIG. 4 is a perspective view of the storage tank 20. FIG. 5 is an exploded perspective view of the storage tank 20. FIG. 6 is a cross-sectional view of the storage tank 20 (VI-VI line cross-sectional view in FIG. 4). In FIG. 6, the sample container 5 is not a cross-sectional view but a side view. As shown in FIG. 4, a plurality of container insertion holes 20b for inserting the sample container 5 are formed on the upper surface 20a of the storage tank 20. Further, as shown in FIG. 5, in the storage tank 20, a supply port 20d for supplying the heat medium 15 into the storage tank 20 is provided on one side surface 20c in the longitudinal direction. In the storage tank 20, a discharge port 20f for discharging the heat medium 15 from the inside of the storage tank 20 is provided on the other side surface 20e in the longitudinal direction.
 収容槽20は、上面が開口した水槽型の容器本体21と、検体容器5を保持する保持部材22と、容器本体21の開口を封止する蓋体23と、供給口20dの側の配管取付用金具24と、排出口20fの側の配管取付用金具25と、を備えている。 The storage tank 20 includes a water tank type container body 21 having an open upper surface, a holding member 22 for holding the sample container 5, a lid 23 for sealing the opening of the container body 21, and piping attachment on the side of the supply port 20d. A metal fitting 24 and a pipe mounting metal fitting 25 on the side of the discharge port 20f are provided.
 容器本体21において、長手方向の一方の側面21cには供給口20dが形成されており、他方の側面21eには排出口20fが形成されている。本実施形態において、容器本体21は、ポリフタルアミドにより構成されている。容器本体21は、ポリフタルアミド(PPA)またはポリフェニレンエーテル(PPE)などの、耐熱性および断熱性が高く、また熱媒体に対する耐薬性が高く、さらに熱容量の小さい樹脂材料により構成することが好ましい。 In the container main body 21, a supply port 20d is formed on one side surface 21c in the longitudinal direction, and a discharge port 20f is formed on the other side surface 21e. In the present embodiment, the container body 21 is made of polyphthalamide. The container body 21 is preferably made of a resin material having high heat resistance and heat insulating properties, high chemical resistance to a heat medium, and a small heat capacity, such as polyphthalamide (PPA) or polyphenylene ether (PPE).
 保持部材22は、平板状の台座部22aと、台座部22a上に設けられた複数の筒状の容器挿入部22bとが、一体的に形成された形状である。保持部材22は、容器本体21の内部に収容される。本実施形態において、保持部材22は、アルミにより構成されている。保持部材22としては、アルミなどの、熱伝導性に優れ、さびにくく、かつ安価で加工性が高い金属材量により構成することが好ましい。 The holding member 22 has a shape in which a flat plate-shaped pedestal portion 22a and a plurality of tubular container insertion portions 22b provided on the pedestal portion 22a are integrally formed. The holding member 22 is housed inside the container body 21. In the present embodiment, the holding member 22 is made of aluminum. The holding member 22 is preferably made of a metal material such as aluminum, which has excellent thermal conductivity, is resistant to rust, is inexpensive, and has high workability.
 蓋体23には、複数の容器挿入孔20bの挿入口23aが形成されている。収容槽20を組み上げた際に、蓋体23の挿入口23aと保持部材22の容器挿入部22bの内部とが連通して、容器挿入孔20bが形成される。本実施形態において、蓋体23は、容器本体21と同様に、ポリフタルアミドにより構成されている。蓋体23としては、ポリフタルアミド(PPA)またはポリフェニレンエーテル(PPE)などの、耐熱性および断熱性が高く、かつ熱媒体に対する耐薬性が高く、さらに熱容量の小さい樹脂材料により構成することが好ましい。 The lid 23 is formed with insertion ports 23a for a plurality of container insertion holes 20b. When the storage tank 20 is assembled, the insertion port 23a of the lid 23 and the inside of the container insertion portion 22b of the holding member 22 communicate with each other to form the container insertion hole 20b. In the present embodiment, the lid 23 is made of polyphthalamide, like the container body 21. The lid 23 is preferably made of a resin material such as polyphthalamide (PPA) or polyphenylene ether (PPE), which has high heat resistance and heat insulating properties, high chemical resistance to a heat medium, and a small heat capacity. ..
 容器挿入孔20bの内径は、検体容器5の外径よりもわずかに大きく形成されているが、ほぼ同径である。そのため、検体容器5を容器挿入孔20bに挿入した際には、検体容器5は容器挿入孔20b内において傾くことなく保持される。 The inner diameter of the container insertion hole 20b is formed to be slightly larger than the outer diameter of the sample container 5, but is substantially the same diameter. Therefore, when the sample container 5 is inserted into the container insertion hole 20b, the sample container 5 is held in the container insertion hole 20b without tilting.
 本実施形態の処理装置10の収容槽20においては、10個の容器挿入孔20bが一列に並べて配置されている。処理装置10は、最大10個までの検体容器5を装填し、同時に前処理を行うことが可能である。 In the storage tank 20 of the processing device 10 of the present embodiment, 10 container insertion holes 20b are arranged side by side in a row. The processing device 10 can be loaded with up to 10 sample containers 5 and can be pretreated at the same time.
 配管取付用金具24は、配管装着部およびボルト結合部が形成された金具本体24aと、ボルト24bと、を備えている。配管取付用金具24は、容器本体21の外側から金具本体24aのボルト結合部を供給口20dに挿入し、かつ、容器本体21の内側から金具本体24aに対してボルト24bを結合させることにより、容器本体21に取り付けられている。配管取付用金具24は、貫通孔を有しており、配管取付用金具24が容器本体21に取り付けられた状態では、配管取付用金具24の貫通孔が供給口20dとして機能する(図6も参照)。 The pipe mounting metal fitting 24 includes a metal fitting body 24a and a bolt 24b in which a pipe mounting portion and a bolt joint portion are formed. The pipe mounting bracket 24 is formed by inserting the bolt coupling portion of the metal fitting body 24a into the supply port 20d from the outside of the container body 21 and connecting the bolt 24b to the metal fitting body 24a from the inside of the container body 21. It is attached to the container body 21. The pipe mounting bracket 24 has a through hole, and when the pipe mounting bracket 24 is attached to the container body 21, the through hole of the pipe mounting bracket 24 functions as a supply port 20d (also in FIG. 6). reference).
 配管取付用金具25も同様に、配管装着部およびボルト結合部が形成された金具本体25aと、ボルト25bと、を備えている。配管取付用金具25は、容器本体21の外側から金具本体25aのボルト結合部を排出口20fに挿入し、かつ、容器本体21の内側から金具本体25aに対してボルト25bを結合させることにより、容器本体21に取り付けられている。配管取付用金具25は、貫通孔を有しており、配管取付用金具25が容器本体21に取り付けられた状態では、配管取付用金具25の貫通孔が排出口20fとして機能する(図6も参照)。 Similarly, the pipe mounting metal fitting 25 also includes a metal fitting body 25a and a bolt 25b in which a pipe mounting portion and a bolt joint portion are formed. The pipe mounting bracket 25 is formed by inserting the bolt coupling portion of the metal fitting body 25a into the discharge port 20f from the outside of the container body 21 and connecting the bolt 25b to the metal fitting body 25a from the inside of the container body 21. It is attached to the container body 21. The pipe mounting bracket 25 has a through hole, and when the pipe mounting bracket 25 is attached to the container body 21, the through hole of the pipe mounting bracket 25 functions as a discharge port 20f (also in FIG. 6). reference).
 図3に戻り、熱媒体交換機構は、第1熱媒体供給部30、第1供給路40、第1排出路44、第2熱媒体供給部31、第2供給路41、および第2排出路45を備えている。収容槽20、第1熱媒体供給部30、第1供給路40および第1排出路44は、第1熱媒体15aの循環路を構成する。第1熱媒体供給部30は、第1供給路40を通じて収容槽20に対して、第1熱媒体15aを供給する。第1熱媒体15aは、収容槽20内の検体容器5に収容された検体溶液Cを第1温度に加熱する。収容槽20に供給された第1熱媒体15aは第1排出路44を通じて収容槽20から排出され、第1排出路44を通じて第1熱媒体供給部30に回収される。 Returning to FIG. 3, the heat medium exchange mechanism includes a first heat medium supply section 30, a first supply path 40, a first discharge path 44, a second heat medium supply section 31, a second supply path 41, and a second discharge path. It has 45. The storage tank 20, the first heat medium supply unit 30, the first supply path 40, and the first discharge path 44 form a circulation path for the first heat medium 15a. The first heat medium supply unit 30 supplies the first heat medium 15a to the accommodating tank 20 through the first supply path 40. The first heat medium 15a heats the sample solution C stored in the sample container 5 in the storage tank 20 to the first temperature. The first heat medium 15a supplied to the storage tank 20 is discharged from the storage tank 20 through the first discharge passage 44, and is collected in the first heat medium supply unit 30 through the first discharge passage 44.
 収容槽20、第2熱媒体供給部31、第2供給路41および第2排出路45は、第2熱媒体15bの循環路を構成する。第2熱媒体供給部31は、第2供給路41を通じて収容槽20に対して、第2熱媒体15bを供給する。第2熱媒体15bは、収容槽20内の検体容器5に収容された検体溶液Cを、第1温度に加熱された状態から第2温度に冷却する。収容槽20に供給された第2熱媒体15bは第2排出路45を通じて収容槽20から排出され、第2排出路45を通じて第2熱媒体供給部31に回収される。 The storage tank 20, the second heat medium supply unit 31, the second supply path 41, and the second discharge path 45 form a circulation path for the second heat medium 15b. The second heat medium supply unit 31 supplies the second heat medium 15b to the accommodating tank 20 through the second supply path 41. The second heat medium 15b cools the sample solution C stored in the sample container 5 in the storage tank 20 from the state heated to the first temperature to the second temperature. The second heat medium 15b supplied to the storage tank 20 is discharged from the storage tank 20 through the second discharge passage 45, and is collected in the second heat medium supply unit 31 through the second discharge passage 45.
 第1供給路40および第2供給路41は、弁32および共通供給路42を介して収容槽20の供給口20dに接続されている。弁32は、第1供給路40と供給口20dを連通させる第1状態と第2供給路41と供給口20dを連通させる第2状態とを切り替える。第1状態では、収容槽20に対する第1熱媒体15aの供給が行われ、第2状態では、収容槽20に対する第2熱媒体15bの供給が行われる。 The first supply path 40 and the second supply path 41 are connected to the supply port 20d of the storage tank 20 via the valve 32 and the common supply path 42. The valve 32 switches between a first state in which the first supply path 40 and the supply port 20d communicate with each other and a second state in which the second supply path 41 and the supply port 20d communicate with each other. In the first state, the first heat medium 15a is supplied to the storage tank 20, and in the second state, the second heat medium 15b is supplied to the storage tank 20.
 第1排出路44および第2排出路45は、弁33および共通排出路43を介して収容槽20の排出口20fに接続されている。弁33は、第1排出路44と排出口20fを連通させる第1状態と第2排出路45と排出口20fを連通させる第2状態とを切り替える。 The first discharge passage 44 and the second discharge passage 45 are connected to the discharge port 20f of the storage tank 20 via the valve 33 and the common discharge passage 43. The valve 33 switches between a first state in which the first discharge path 44 and the discharge port 20f communicate with each other and a second state in which the second discharge path 45 and the discharge port 20f communicate with each other.
 第1熱媒体供給部30は、熱媒体15aを貯留する貯留部30aと、貯留部30aに貯留されている熱媒体15を第1熱媒体15aとするために加熱するヒーター30bと、ポンプ30dと、貯留部30aの排出口とポンプ30dの供給口とを接続する配管30cと、を備えている。 The first heat medium supply unit 30 includes a storage unit 30a for storing the heat medium 15a, a heater 30b for heating the heat medium 15 stored in the storage unit 30a as the first heat medium 15a, and a pump 30d. A pipe 30c for connecting the discharge port of the storage unit 30a and the supply port of the pump 30d is provided.
 比濁法によりエンドトキシン測定を行う場合の検体溶液Cに対する前処理としては、30℃以上80℃以下で加熱することが好ましい。そのため、ヒーター30bの温度は、30℃以上80℃以下に設定可能である。なお、ヒーター30bの温度は、60℃以上80℃以下とすることがより好ましい。本実施形態では、制御部11からの制御に基づいて、ヒーター30bの温度は、70℃(第1温度の一例)に設定される。 As a pretreatment for the sample solution C when endotoxin measurement is performed by the turbidimetry method, it is preferable to heat at 30 ° C. or higher and 80 ° C. or lower. Therefore, the temperature of the heater 30b can be set to 30 ° C. or higher and 80 ° C. or lower. The temperature of the heater 30b is more preferably 60 ° C. or higher and 80 ° C. or lower. In the present embodiment, the temperature of the heater 30b is set to 70 ° C. (an example of the first temperature) based on the control from the control unit 11.
 第1供給路40は、ポンプ30dの排出口と弁32の接続口32aとを接続する配管により構成されている。 The first supply path 40 is composed of a pipe connecting the discharge port of the pump 30d and the connection port 32a of the valve 32.
 第1排出路44は、弁33の接続口33aと第1熱媒体供給部30の供給口とを接続する配管により構成されている。 The first discharge passage 44 is composed of a pipe connecting the connection port 33a of the valve 33 and the supply port of the first heat medium supply unit 30.
 第2熱媒体供給部31は、熱媒体15を貯留する貯留部31aと、貯留部31aに貯留されている熱媒体15を第2熱媒体15bとするために冷却する冷却素子31bと、ポンプ31dと、貯留部31aの排出口とポンプ31dの供給口とを接続する配管31cと、を備えている。 The second heat medium supply unit 31 includes a storage unit 31a for storing the heat medium 15, a cooling element 31b for cooling the heat medium 15 stored in the storage unit 31a to be the second heat medium 15b, and a pump 31d. And a pipe 31c for connecting the discharge port of the storage unit 31a and the supply port of the pump 31d.
 比濁法によりエンドトキシン測定を行う場合の検体溶液Cに対する前処理としては、0℃以上10℃以下で冷却することが好ましい。そのため、冷却素子31bの温度は、0℃以上10℃以下に設定可能である。本実施形態では、制御部11からの制御に基づいて、冷却素子31bの温度は、5℃(第2温度の一例)に設定される。冷却素子31bとしては、ペルチェ素子を用いる。 As a pretreatment for the sample solution C when endotoxin measurement is performed by the turbidimetry method, it is preferable to cool at 0 ° C. or higher and 10 ° C. or lower. Therefore, the temperature of the cooling element 31b can be set to 0 ° C. or higher and 10 ° C. or lower. In the present embodiment, the temperature of the cooling element 31b is set to 5 ° C. (an example of the second temperature) based on the control from the control unit 11. As the cooling element 31b, a Perche element is used.
 第2供給路41は、ポンプ31dの排出口と弁32の接続口32bとを接続する配管により構成されている。 The second supply path 41 is composed of a pipe connecting the discharge port of the pump 31d and the connection port 32b of the valve 32.
 第2排出路45は、弁33の接続口33bと第2熱媒体供給部31の供給口とを接続する配管により構成されている。 The second discharge passage 45 is composed of a pipe connecting the connection port 33b of the valve 33 and the supply port of the second heat medium supply unit 31.
 弁32は、三方弁であり、第1供給路40が接続される接続口32aと、第2供給路41が接続される接続口32bと、弁32と供給口20dとを接続する共通供給路42が接続される接続口32cと、を備える。弁32は、制御部11からの制御に基づいて、第1供給路40と供給口20dを連通させる第1状態と、第2供給路41と供給口20dを連通させる第2状態とを切り替え可能に構成されている。第1状態では、接続口32aと接続口32cとが内部で連通する。第2状態では、接続口32bと接続口32cとが内部で連通する。共通供給路42は、接続口32cと供給口20dとを接続する配管により構成されている。 The valve 32 is a three-way valve, and is a common supply path connecting the connection port 32a to which the first supply path 40 is connected, the connection port 32b to which the second supply path 41 is connected, and the valve 32 and the supply port 20d. A connection port 32c to which the 42 is connected is provided. The valve 32 can switch between a first state in which the first supply path 40 and the supply port 20d communicate with each other and a second state in which the second supply path 41 and the supply port 20d communicate with each other based on the control from the control unit 11. It is configured in. In the first state, the connection port 32a and the connection port 32c communicate with each other internally. In the second state, the connection port 32b and the connection port 32c communicate with each other internally. The common supply path 42 is composed of a pipe connecting the connection port 32c and the supply port 20d.
 弁33は、三方弁であり、第1排出路44が接続される接続口33aと、第2排出路45が接続される接続口33bと、弁33と排出口20fとを接続する共通排出路43が接続される接続口33cと、を備える。弁33は、制御部11からの制御に基づいて、第1排出路44と排出口20fを連通させる第1状態と、第2排出路45と排出口20fを連通させる第2状態とを切り替え可能に構成されている。第1状態では、接続口33aと接続口33cとが内部で連通する。第2状態では、接続口33bと接続口33cとが内部で連通する。共通排出路43は、排出口20fと接続口33cとを接続する配管により構成されている。 The valve 33 is a three-way valve, and is a common discharge path that connects the connection port 33a to which the first discharge path 44 is connected, the connection port 33b to which the second discharge path 45 is connected, and the valve 33 and the discharge port 20f. A connection port 33c to which the 43 is connected is provided. The valve 33 can switch between a first state in which the first discharge path 44 and the discharge port 20f communicate with each other and a second state in which the second discharge path 45 and the discharge port 20f communicate with each other based on the control from the control unit 11. It is configured in. In the first state, the connection port 33a and the connection port 33c communicate with each other internally. In the second state, the connection port 33b and the connection port 33c communicate with each other internally. The common discharge path 43 is composed of a pipe connecting the discharge port 20f and the connection port 33c.
 制御部11は、CPU(Central Processing Unit)11aと、メモリ11bと、制御用プログラムが格納されたストレージ11cと、を備えている。メモリ11bは、CPU11aが制御用プログラムを実行する際に使用するワークメモリであり、例えば揮発性メモリが使用される。ストレージ11cは、種々のデータを格納するための不揮発性メモリであり、フラッシュメモリなどが使用される。制御部11は、制御用プログラムを実行することにより、ヒーター30b、ポンプ30d、冷却素子31b、ポンプ31d、弁32、および弁33の各部を制御する制御部として機能する。 The control unit 11 includes a CPU (Central Processing Unit) 11a, a memory 11b, and a storage 11c in which a control program is stored. The memory 11b is a work memory used by the CPU 11a when executing a control program, and for example, a volatile memory is used. The storage 11c is a non-volatile memory for storing various data, and a flash memory or the like is used. The control unit 11 functions as a control unit that controls each unit of the heater 30b, the pump 30d, the cooling element 31b, the pump 31d, the valve 32, and the valve 33 by executing the control program.
<測定装置>
 図7は、測定装置60の構成を示す概略図である。図7に示すように、測定装置60は、検体容器5に対して測定光を照射するLED(Light Emitting Diode)61と、検体容器5を挟んでLED61と対向する位置に配されたPD(Photodiode)62と、測定制御部63と、を備える。測定制御部63は、PD62の検出結果に基づいて検体溶液E中のエンドトキシン量の測定を行う。また、測定制御部63は、LED61およびPD62を制御する。検体容器5内には、前処理後の検体溶液Cとライセート試薬Dとが混合された検体溶液Eが収容される。
<Measuring device>
FIG. 7 is a schematic view showing the configuration of the measuring device 60. As shown in FIG. 7, the measuring device 60 includes an LED (Light Emitting Diode) 61 that irradiates the sample container 5 with measurement light, and a PD (Photodiode) arranged at a position facing the LED 61 across the sample container 5. ) 62 and a measurement control unit 63. The measurement control unit 63 measures the amount of endotoxin in the sample solution E based on the detection result of PD62. Further, the measurement control unit 63 controls the LED 61 and the PD 62. The sample container 5 contains a sample solution E in which the pretreated sample solution C and the lysate reagent D are mixed.
 測定制御部63は、CPU(Central Processing Unit)63aと、メモリ63bと、測定制御用プログラムが格納されたストレージ63cと、を備えている。メモリ63bは、CPU63aが測定制御用プログラムを実行する際に使用するワークメモリであり、例えば揮発性メモリが使用される。ストレージ63cは、種々のデータを格納するための不揮発性メモリであり、フラッシュメモリなどが使用される。測定制御部63は、測定制御用プログラムを実行することにより、LED61およびPD62の各部を制御する制御部として機能する。また、測定制御部63は、測定制御用プログラムを実行することにより、PD62の検出結果に基づいて検体溶液E中のエンドトキシン量の測定を行う測定部として機能する。 The measurement control unit 63 includes a CPU (Central Processing Unit) 63a, a memory 63b, and a storage 63c in which a measurement control program is stored. The memory 63b is a work memory used by the CPU 63a when executing a measurement control program, and for example, a volatile memory is used. The storage 63c is a non-volatile memory for storing various data, and a flash memory or the like is used. The measurement control unit 63 functions as a control unit that controls each unit of the LED 61 and the PD 62 by executing the measurement control program. Further, the measurement control unit 63 functions as a measurement unit that measures the amount of endotoxin in the sample solution E based on the detection result of PD62 by executing the measurement control program.
 測定装置60におけるエンドトキシン測定の手法としては、上述のとおり比濁法が用いられる。比濁法は、エンドトキシンの作用によりライセート試薬Dがゲル化する過程での濁度変化を指標とする手法である。検体溶液E中のエンドトキシンの量と、前処理後の検体溶液Cに対してライセート試薬Dを添加してからの経過時間とに応じて、検体溶液Eの濁度に変化が生じる。検体溶液Eの濁度が変化すると、検体溶液Eを透過する測定光の光量が変化するため、PD62により透過光量の経時変化を測定することにより、検体溶液Eの濁度の状態および推移を測定することができる。測定制御部63は、検体溶液Eの濁度の状態および推移に基づいて、検体溶液E中のエンドトキシン量の演算を行う。 As a method for measuring endotoxin in the measuring device 60, the turbidimetry method is used as described above. The turbidimetry method is a method using the change in turbidity in the process of gelation of lysate reagent D by the action of endotoxin as an index. The turbidity of the sample solution E changes depending on the amount of endotoxin in the sample solution E and the elapsed time from the addition of the lysate reagent D to the sample solution C after the pretreatment. When the turbidity of the sample solution E changes, the amount of measurement light transmitted through the sample solution E changes. Therefore, the state and transition of the turbidity of the sample solution E are measured by measuring the change over time in the amount of transmitted light with the PD62. can do. The measurement control unit 63 calculates the amount of endotoxin in the sample solution E based on the state and transition of the turbidity of the sample solution E.
[前処理の流れ]
 図8は、処理装置10における前処理の流れを説明するためのフローチャートである。
[Preprocessing flow]
FIG. 8 is a flowchart for explaining the flow of preprocessing in the processing apparatus 10.
 まず、検体Aに緩衝液Bを加えて希釈することにより検体溶液Cが生成される。生成された検体溶液Cが収容された検体容器5は、収容槽20の容器挿入孔20bに挿入される。この後、制御部11は、第1熱媒体15aを収容槽20内に供給を開始し、第1熱媒体15aの循環を開始させる(ステップS1)。詳細には、制御部11は、弁32に対して、第1供給路40と供給口20dを連通させる第1状態に切り替える制御を行う。また、弁33に対して、第1排出路44と排出口20fを連通させる第1状態に切り替える制御を行う。次に、制御部11は、ポンプ30dを駆動し、図9中に矢印で示すように、第1熱媒体供給部30内の第1熱媒体15aを、第1供給路40および第1排出路44を通じて収容槽20内に循環させる制御を行う。 First, sample solution C is produced by adding buffer solution B to sample A and diluting it. The sample container 5 containing the generated sample solution C is inserted into the container insertion hole 20b of the storage tank 20. After that, the control unit 11 starts supplying the first heat medium 15a into the storage tank 20 and starts the circulation of the first heat medium 15a (step S1). Specifically, the control unit 11 controls the valve 32 to switch to the first state in which the first supply path 40 and the supply port 20d communicate with each other. Further, the valve 33 is controlled to switch to the first state in which the first discharge path 44 and the discharge port 20f communicate with each other. Next, the control unit 11 drives the pump 30d, and as shown by an arrow in FIG. 9, the first heat medium 15a in the first heat medium supply unit 30 is connected to the first supply path 40 and the first discharge path. Control is performed to circulate in the storage tank 20 through 44.
 次に、制御部11は、収容槽20内への第1熱媒体15aの循環を開始してから10分が経過したか否かの判定を行う(ステップS2)。ステップS2において、10分が経過していないと判定された場合(判定結果No)、制御部11は、収容槽20内への第1熱媒体15aの循環を継続する。 Next, the control unit 11 determines whether or not 10 minutes have passed since the circulation of the first heat medium 15a into the storage tank 20 was started (step S2). If it is determined in step S2 that 10 minutes have not passed (determination result No.), the control unit 11 continues to circulate the first heat medium 15a into the storage tank 20.
 ステップS2において、10分が経過したと判定された場合(判定結果Yes)、制御部11は、収容槽20内への第1熱媒体15aの循環を停止し、第2熱媒体15bを収容槽20内に循環させる(ステップS3)。詳細には、制御部11は、弁32に対して、第2供給路41と供給口20dを連通させる第2状態に切り替える制御を行う。また、弁33に対して、第2排出路45と排出口20fを連通させる第2状態に切り替える制御を行う。次に、制御部11は、ポンプ31dを駆動し、図10中に矢印で示すように、第2熱媒体供給部31内の第2熱媒体15bを、第2供給路41および第2排出路45を通じて収容槽20内に循環させる制御を行う。 When it is determined in step S2 that 10 minutes have passed (determination result Yes), the control unit 11 stops the circulation of the first heat medium 15a into the storage tank 20 and puts the second heat medium 15b in the storage tank. Circulate within 20 (step S3). Specifically, the control unit 11 controls the valve 32 to switch to the second state in which the second supply path 41 and the supply port 20d communicate with each other. Further, the valve 33 is controlled to switch to the second state in which the second discharge path 45 and the discharge port 20f communicate with each other. Next, the control unit 11 drives the pump 31d, and as shown by an arrow in FIG. 10, connects the second heat medium 15b in the second heat medium supply unit 31 to the second supply path 41 and the second discharge path. Control is performed to circulate in the storage tank 20 through 45.
 次に、制御部11は、収容槽20内への第2熱媒体15bの循環を開始してから3分が経過したか否かの判定を行う(ステップS4)。ステップS4において、3分が経過していないと判定された場合(判定結果No)、制御部11は、収容槽20内への第2熱媒体15bの循環を継続する。 Next, the control unit 11 determines whether or not 3 minutes have passed since the circulation of the second heat medium 15b into the storage tank 20 was started (step S4). When it is determined in step S4 that 3 minutes have not passed (determination result No.), the control unit 11 continues the circulation of the second heat medium 15b into the storage tank 20.
 ステップS4において、3分が経過したと判定された場合(判定結果Yes)、制御部11は、収容槽20内への第2熱媒体15aの循環を停止する制御を行い、処理を終了する。 In step S4, when it is determined that 3 minutes have passed (determination result Yes), the control unit 11 controls to stop the circulation of the second heat medium 15a into the accommodation tank 20 and ends the process.
[作用効果]
 本実施形態の処理装置10は、以上で説明したように、検体容器5を収容し、かつ、検体容器5内の検体溶液Cの温度を変化させるための流体状の熱媒体15を検体容器5の周囲に貯留することが可能な収容槽20と、収容槽20内の熱媒体15を交換する熱媒体交換機構であって、検体容器5内の検体溶液Cを第1温度に加熱するための第1熱媒体15aと、第1温度よりも低い第2温度に検体溶液Cを冷却するための第2熱媒体15bとを交換する熱媒体交換機構と、を備える。
[Action effect]
As described above, the processing apparatus 10 of the present embodiment contains the sample container 5 and provides the sample container 5 with a fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5. A heat medium exchange mechanism for exchanging a heat medium 15 in a storage tank 20 with a storage tank 20 capable of storing the sample solution C in the sample container 5 to heat the sample solution C to a first temperature. A heat medium exchange mechanism for exchanging a first heat medium 15a and a second heat medium 15b for cooling the sample solution C to a second temperature lower than the first temperature is provided.
 このような構成とすることにより、検体容器5を収容槽20に装填したまま、検体容器5内の検体溶液Cに対して加熱と冷却の両方を行うことができる。これにより、加熱部と冷却部が個別に設けられている従来の処理装置のように、検体容器を加熱部から冷却部まで搬送するハンドリングロボットのような搬送機構を設ける必要がなくなるため、検体容器の搬送不良の問題を解消することができる。 With such a configuration, it is possible to both heat and cool the sample solution C in the sample container 5 while the sample container 5 is loaded in the storage tank 20. This eliminates the need to provide a transport mechanism such as a handling robot that transports the sample container from the heating unit to the cooling unit, unlike the conventional processing device in which the heating unit and the cooling unit are separately provided. It is possible to solve the problem of poor transportation.
 また、収容槽20に複数の検体容器5を装填した場合でも、複数の検体容器5を移動させることなく、加熱と冷却の両方を行うことができる。そのため、従来の処理装置のように、ハンドリングロボットによって検体容器を1個ずつ搬送する場合と比較して、処理時間を短縮することができる。 Further, even when a plurality of sample containers 5 are loaded in the storage tank 20, both heating and cooling can be performed without moving the plurality of sample containers 5. Therefore, the processing time can be shortened as compared with the case where the sample containers are transported one by one by the handling robot as in the conventional processing apparatus.
 また、本実施形態の処理装置10においては、収容槽20には、熱媒体15を供給する供給口20dと、熱媒体15を排出する排出口20fとが設けられており、熱媒体交換機構は、供給口20dと排出口20fとに接続された配管を通じて、収容槽20内の第1熱媒体15aまたは第2熱媒体15bを循環させるように構成されている。 Further, in the processing apparatus 10 of the present embodiment, the storage tank 20 is provided with a supply port 20d for supplying the heat medium 15 and a discharge port 20f for discharging the heat medium 15, and the heat medium exchange mechanism is provided. The first heat medium 15a or the second heat medium 15b in the storage tank 20 is circulated through the pipes connected to the supply port 20d and the discharge port 20f.
 第1熱媒体15aまたは第2熱媒体15bを循環させることにより、収容槽20から排出された第1熱媒体15aまたは第2熱媒体15bを設定温度に復帰させやすく、収容槽20に対して供給する第1熱媒体15aまたは第2熱媒体15bを設定温度に維持しやすい。そのため、第1熱媒体15aまたは第2熱媒体15bを循環させない場合と比べて、加熱または冷却を迅速に行いやすい。 By circulating the first heat medium 15a or the second heat medium 15b, the first heat medium 15a or the second heat medium 15b discharged from the storage tank 20 can be easily returned to the set temperature and supplied to the storage tank 20. It is easy to maintain the first heat medium 15a or the second heat medium 15b at a set temperature. Therefore, it is easier to heat or cool the heat medium 15a or the second heat medium 15b more quickly than in the case where the first heat medium 15a or the second heat medium 15b is not circulated.
 また、本実施形態の処理装置10は、第1熱媒体15aを供給する第1熱媒体供給部30に接続される第1供給路と、第2熱媒体15bを供給する第2熱媒体供給部31に接続される第2供給路と、第1供給路と供給口20dを連通させる第1状態と、第2供給路と供給口20dを連通させる第2状態とを切り替える弁32と、を備える。 Further, the processing apparatus 10 of the present embodiment has a first supply path connected to a first heat medium supply unit 30 that supplies the first heat medium 15a, and a second heat medium supply unit that supplies the second heat medium 15b. A second supply path connected to 31 and a valve 32 for switching between a first state for communicating the first supply path and the supply port 20d and a second state for communicating the second supply path and the supply port 20d are provided. ..
 このように弁32を設けることで、温度が異なる第1熱媒体15aと第2熱媒体16bの供給路を区別することができる。供給路を区別すると、本例で示したように、第1熱媒体供給部30と、第2熱媒体供給部31とを別々に設けることができる。そのため、第1熱媒体15aと第2熱媒体15bとを個別に用意し、いずれかを選択的に収容槽20内に供給する構成となるため、安定した温度の第1熱媒体15aまたは第2熱媒体15bを供給することができる。 By providing the valve 32 in this way, it is possible to distinguish between the supply paths of the first heat medium 15a and the second heat medium 16b having different temperatures. When the supply paths are distinguished, as shown in this example, the first heat medium supply unit 30 and the second heat medium supply unit 31 can be provided separately. Therefore, the first heat medium 15a and the second heat medium 15b are prepared separately, and one of them is selectively supplied into the storage tank 20, so that the first heat medium 15a or the second heat medium 15a or the second heat medium having a stable temperature can be selectively supplied. The heat medium 15b can be supplied.
 また、熱媒体15として、気体と比較して比熱が大きい液体を用いると次のような効果がある。熱媒体15は、比熱が大きい方が温まりにくく冷めにくい。検体溶液Cを加熱する場合において、比熱が大きい(すなわち、冷めにくい)熱媒体15を用いて加熱する方が、相対的に比熱が小さい(すなわち、冷めやすい)熱媒体15を用いる場合と比べて、熱媒体15が加熱された状態が維持されることになるため、検体溶液Cを迅速に加熱することができる。検体溶液Cを冷却する場合も、比熱が大きい(すなわち、温まりにくい)熱媒体15を用いれば、相対的に比熱が小さい(すなわち、温まりやすい)熱媒体15を用いる場合と比べて、熱媒体15が冷却された状態が維持されることになるため、検体溶液Cを迅速に冷却することができる。 Further, when a liquid having a larger specific heat than a gas is used as the heat medium 15, the following effects are obtained. The heat medium 15 is harder to heat and cool when the specific heat is larger. When heating the sample solution C, it is more likely to heat the sample solution C using a heat medium 15 having a large specific heat (that is, difficult to cool) than to use a heat medium 15 having a relatively small specific heat (that is, easy to cool). Since the heat medium 15 is maintained in a heated state, the sample solution C can be heated quickly. Even when the sample solution C is cooled, if the heat medium 15 having a large specific heat (that is, difficult to warm) is used, the heat medium 15 is compared with the case where the heat medium 15 having a relatively small specific heat (that is, easy to warm) is used. Since the cooled state is maintained, the sample solution C can be cooled quickly.
 また、本実施形態の処理装置10においては、熱媒体15として純水を用いている。純水は、不純物が少なく腐食しづらいため、上記の効果に加えて、熱媒体交換機構の配管の詰まりの防止にも寄与する。 Further, in the processing apparatus 10 of the present embodiment, pure water is used as the heat medium 15. Since pure water has few impurities and is hard to corrode, in addition to the above effects, it also contributes to the prevention of clogging of the piping of the heat medium exchange mechanism.
 また、収容槽20に第1熱媒体15aが供給されてから予め設定された設定時間が経過した後、熱媒体交換機構を制御することにより、収容槽20に第2熱媒体15bを供給させる制御部11を備えることにより、前処理の自動化を行うことができる。 Further, control for supplying the second heat medium 15b to the storage tank 20 by controlling the heat medium exchange mechanism after a preset set time has elapsed since the first heat medium 15a was supplied to the storage tank 20. By providing the unit 11, the preprocessing can be automated.
 また、熱媒体15を第1熱媒体15aとするために加熱するヒーター30bを備え、このヒーター30bの温度を30℃以上80℃以下に設定することにより、比濁法によるエンドトキシン測定用の前処理に適した加熱処理を行うことができる。なお、ヒーター30bの温度を60℃以上80℃以下に設定することにより、加熱処理をより効率的に行うことができる。 Further, a heater 30b for heating the heat medium 15 as the first heat medium 15a is provided, and by setting the temperature of the heater 30b to 30 ° C. or higher and 80 ° C. or lower, pretreatment for endotoxin measurement by the turbidimetry method is performed. It is possible to carry out a heat treatment suitable for. By setting the temperature of the heater 30b to 60 ° C. or higher and 80 ° C. or lower, the heat treatment can be performed more efficiently.
 また、熱媒体15を第2熱媒体15bとするために冷却する冷却素子31bを備え、この冷却素子31bの温度を0℃以上10℃以下に設定することにより、比濁法によるエンドトキシン測定用の前処理に適した冷却処理を行うことができる。 Further, a cooling element 31b for cooling the heat medium 15 as the second heat medium 15b is provided, and by setting the temperature of the cooling element 31b to 0 ° C. or higher and 10 ° C. or lower, endotoxin measurement by the turbidimetric method can be performed. A cooling process suitable for the pretreatment can be performed.
「第2実施形態」
 上記測定システム1は、処理装置10について、第2実施形態に係る処理装置10Bに変更することができる。なお、処理装置10B以外の構成については、第1実施形態と同じであるため、処理装置10B以外の説明は省略する。
"Second embodiment"
The measurement system 1 can change the processing device 10 to the processing device 10B according to the second embodiment. Since the configurations other than the processing device 10B are the same as those in the first embodiment, the description other than the processing device 10B will be omitted.
<処理装置>
 図11は、第2実施形態に係る処理装置10Bの構成を示す概略図である。図11に示すように、処理装置10Bは、検体容器5を収容し、かつ、検体容器5内の検体溶液Cの温度を変化させるための流体状の熱媒体15を貯留することが可能な収容槽20と、収容槽20内の熱媒体を交換する熱媒体交換機構と、熱媒体交換機構を制御する制御部12と、を備える。
<Processing device>
FIG. 11 is a schematic view showing the configuration of the processing apparatus 10B according to the second embodiment. As shown in FIG. 11, the processing apparatus 10B accommodates the sample container 5 and can store the fluid heat medium 15 for changing the temperature of the sample solution C in the sample container 5. The tank 20 includes a heat medium exchange mechanism for exchanging the heat medium in the accommodating tank 20, and a control unit 12 for controlling the heat medium exchange mechanism.
 収容槽20は、第1実施形態に係る処理装置10と同じであるため、説明は省略する。 Since the storage tank 20 is the same as the processing device 10 according to the first embodiment, the description thereof will be omitted.
 熱媒体交換機構は、熱媒体供給部34と、熱媒体供給部34から供給される熱媒体15を収容槽20の供給口20dに供給する供給路46と、供給路46上に配置され、供給口20dに供給される前に熱媒体15を第1温度以上に加熱することにより第1熱媒体15aに変換する第1温度調整部35と、供給路46上に配置され、供給口20dに供給される前に熱媒体15を第2温度以下に冷却することにより第2熱媒体15bに変換する第2温度調整部36と、収容槽20から排出される熱媒体15を熱媒体供給部34に戻すための排出路47と、を備えている。 The heat medium exchange mechanism is arranged and supplied on the heat medium supply unit 34, the supply path 46 for supplying the heat medium 15 supplied from the heat medium supply unit 34 to the supply port 20d of the storage tank 20, and the supply path 46. A first temperature adjusting unit 35 that converts the heat medium 15 into a first heat medium 15a by heating the heat medium 15 to a first temperature or higher before being supplied to the port 20d, and a first temperature adjusting unit 35 that is arranged on the supply path 46 and supplied to the supply port 20d. A second temperature adjusting unit 36 that converts the heat medium 15 into a second heat medium 15b by cooling the heat medium 15 to a second temperature or lower, and a heat medium 15 discharged from the storage tank 20 are sent to the heat medium supply unit 34. It is provided with a discharge path 47 for returning.
 熱媒体供給部34は、熱媒体15を貯留する貯留部34aと、ポンプ34cと、貯留部34aの排出口とポンプ34cの供給口とを接続する配管34bと、を備えている。 The heat medium supply unit 34 includes a storage unit 34a for storing the heat medium 15, a pump 34c, and a pipe 34b for connecting the discharge port of the storage unit 34a and the supply port of the pump 34c.
 供給路46は、ポンプ34cの排出口と収容槽20の供給口20dとを接続する配管により構成されている。 The supply path 46 is composed of a pipe connecting the discharge port of the pump 34c and the supply port 20d of the storage tank 20.
 第1温度調整部35は、ヒーターを備えている。比濁法によりエンドトキシン測定を行う場合の検体溶液Cに対する前処理としては、60℃以上80℃以下で加熱することが好ましい。本実施形態では、第1熱媒体15aの温度を70℃とする。制御部12からの制御に基づいて、ヒーターの温度は、供給路46の第1温度調整部35の取り付け位置を通過する熱媒体15の温度が70℃となるように設定される。 The first temperature adjusting unit 35 is provided with a heater. As a pretreatment for the sample solution C when endotoxin measurement is performed by the turbidimetry method, it is preferable to heat at 60 ° C. or higher and 80 ° C. or lower. In the present embodiment, the temperature of the first heat medium 15a is 70 ° C. Based on the control from the control unit 12, the temperature of the heater is set so that the temperature of the heat medium 15 passing through the mounting position of the first temperature adjusting unit 35 of the supply path 46 is 70 ° C.
 第2温度調整部36は、冷却素子であるペルチェ素子を備えている。比濁法によりエンドトキシン測定を行う場合の検体溶液Cに対する前処理としては、0℃以上10℃以下で冷却することが好ましい。本実施形態では、第2熱媒体15bの温度を5℃とする。制御部12からの制御に基づいて、冷却素子の温度は、供給路46の第2温度調整部36の取り付け位置を通過する熱媒体15の温度が5℃となるように設定される。 The second temperature adjusting unit 36 includes a Perche element which is a cooling element. As a pretreatment for the sample solution C when endotoxin measurement is performed by the turbidimetry method, it is preferable to cool at 0 ° C. or higher and 10 ° C. or lower. In the present embodiment, the temperature of the second heat medium 15b is set to 5 ° C. Based on the control from the control unit 12, the temperature of the cooling element is set so that the temperature of the heat medium 15 passing through the mounting position of the second temperature adjusting unit 36 of the supply path 46 is 5 ° C.
 排出路47は、収容槽20の排出口20fと貯留部34aの供給口とを接続する配管により構成されている。 The discharge path 47 is composed of a pipe connecting the discharge port 20f of the storage tank 20 and the supply port of the storage unit 34a.
 図12は、第1温度調整部35および第2温度調整部36の周辺の構造を示す断面図である。図12に示すように、第1温度調整部35は、供給路46に密着するように取り付けられており、供給路46内の第1温度調整部35の取り付け位置を通過する熱媒体15を瞬時に第1熱媒体15aに変換する。供給路46の断面形状は、例えば、紙面と平行な方向の厚みが薄く、厚みに対して紙面と直交する方向の奥行が長い扁平な形状をしている。第1温度調整部35は、供給路46との接触面積が大きくなるように、供給路46の奥行方向に延びている。このため、第1温度調整部35の取り付け位置を通過する単位時間当たりの熱媒体15の量が少ないため、熱媒体15を瞬時に加熱することができる。 FIG. 12 is a cross-sectional view showing the peripheral structures of the first temperature adjusting unit 35 and the second temperature adjusting unit 36. As shown in FIG. 12, the first temperature adjusting unit 35 is attached so as to be in close contact with the supply path 46, and the heat medium 15 passing through the attachment position of the first temperature adjusting unit 35 in the supply path 46 is instantaneously passed. Is converted into the first heat medium 15a. The cross-sectional shape of the supply path 46 is, for example, a flat shape having a thin thickness in the direction parallel to the paper surface and a long depth in the direction orthogonal to the paper surface with respect to the thickness. The first temperature adjusting unit 35 extends in the depth direction of the supply path 46 so that the contact area with the supply path 46 becomes large. Therefore, since the amount of the heat medium 15 per unit time passing through the mounting position of the first temperature adjusting unit 35 is small, the heat medium 15 can be heated instantaneously.
 また、第2温度調整部36も第1温度調整部35と同様に、供給路46内の第2温度調整部36の取り付け位置を通過する熱媒体15を瞬時に第2熱媒体15bに変換する。第2温度調整部36も第1温度調整部35と同様に、供給路46に密着するように取り付けられており、供給路46との接触面積が大きくなるように、供給路46の奥行方向に延びている。これにより、第2温度調整部36の取り付け位置を通過する単位時間当たりの熱媒体15の量が少ないため、熱媒体15を瞬時に冷却することができる。 Further, the second temperature adjusting unit 36 also instantly converts the heat medium 15 passing through the mounting position of the second temperature adjusting unit 36 in the supply path 46 into the second heat medium 15b, similarly to the first temperature adjusting unit 35. .. Like the first temperature adjusting unit 35, the second temperature adjusting unit 36 is also attached so as to be in close contact with the supply path 46, and is oriented in the depth direction of the supply path 46 so that the contact area with the supply path 46 becomes large. It is extending. As a result, since the amount of the heat medium 15 per unit time passing through the mounting position of the second temperature adjusting unit 36 is small, the heat medium 15 can be cooled instantly.
 図11に戻り、制御部12は、CPU(Central Processing Unit)12aと、メモリ12bと、制御用プログラムが格納されたストレージ12cと、を備えている。制御部12は、制御用プログラムを実行することにより、ポンプ34c、第1温度調整部35、および第2温度調整部36の各部を制御する制御部として機能する。 Returning to FIG. 11, the control unit 12 includes a CPU (Central Processing Unit) 12a, a memory 12b, and a storage 12c in which a control program is stored. The control unit 12 functions as a control unit that controls each unit of the pump 34c, the first temperature adjustment unit 35, and the second temperature adjustment unit 36 by executing the control program.
[前処理の流れ]
 図8(第1実施形態と共通)は、処理装置10Bにおける前処理の流れを説明するためのフローチャートである。
[Preprocessing flow]
FIG. 8 (common to the first embodiment) is a flowchart for explaining the flow of preprocessing in the processing apparatus 10B.
 検体Aに緩衝液Bを加えて希釈することにより生成した検体溶液Cが収容された検体容器5が、収容槽20の容器挿入孔20bに挿入された後、制御部12は、第1熱媒体15aを収容槽20内に循環させる(ステップS1)。詳細には、制御部12は、ポンプ34cおよび第1温度調整部35を駆動して、供給路46内を通過する熱媒体15を第1熱媒体15aに変換し、図11中に矢印で示すように、第1熱媒体15aを収容槽20内に循環させる制御を行う。 After the sample container 5 containing the sample solution C produced by adding the buffer solution B to the sample A and diluting it is inserted into the container insertion hole 20b of the storage tank 20, the control unit 12 sets the first heat medium. 15a is circulated in the storage tank 20 (step S1). Specifically, the control unit 12 drives the pump 34c and the first temperature adjusting unit 35 to convert the heat medium 15 passing through the supply path 46 into the first heat medium 15a, which is indicated by an arrow in FIG. As described above, the control is performed so that the first heat medium 15a is circulated in the storage tank 20.
 次に、制御部12は、収容槽20内への第1熱媒体15aの循環を開始してから10分が経過したか判定を行う(ステップS2)。ステップS2において、10分が経過していないと判定された場合(判定結果No)、制御部12は、収容槽20内への第1熱媒体15aの循環を継続する。 Next, the control unit 12 determines whether 10 minutes have passed since the circulation of the first heat medium 15a into the storage tank 20 was started (step S2). If it is determined in step S2 that 10 minutes have not passed (determination result No.), the control unit 12 continues to circulate the first heat medium 15a into the storage tank 20.
 ステップS2において、10分が経過したと判定された場合(判定結果Yes)、制御部12は、収容槽20内への第1熱媒体15aの循環を停止し、第2熱媒体15bを収容槽20内に循環させる(ステップS3)。詳細には、制御部12は、ポンプ34cを駆動したまま、第1温度調整部35の駆動を停止するとともに第2温度調整部36を駆動して、供給路46内を通過する熱媒体15を第2熱媒体15bに変換し、図11中に矢印で示すように、第2熱媒体15bを収容槽20内に循環させる制御を行う。 When it is determined in step S2 that 10 minutes have passed (determination result Yes), the control unit 12 stops the circulation of the first heat medium 15a into the storage tank 20 and puts the second heat medium 15b in the storage tank. Circulate within 20 (step S3). Specifically, the control unit 12 stops driving the first temperature adjusting unit 35 and drives the second temperature adjusting unit 36 while driving the pump 34c to drive the heat medium 15 passing through the supply path 46. It is converted into a second heat medium 15b, and as shown by an arrow in FIG. 11, the second heat medium 15b is controlled to be circulated in the storage tank 20.
 次に、制御部12は、収容槽20内への第2熱媒体15bの循環を開始してから3分が経過したか判定を行う(ステップS4)。ステップS4において、3分が経過していないと判定された場合(判定結果No)、制御部12は、収容槽20内への第2熱媒体15bの循環を継続する。 Next, the control unit 12 determines whether 3 minutes have passed since the circulation of the second heat medium 15b into the storage tank 20 was started (step S4). If it is determined in step S4 that 3 minutes have not passed (determination result No.), the control unit 12 continues to circulate the second heat medium 15b into the storage tank 20.
 ステップS4において、3分が経過したと判定された場合(判定結果Yes)、制御部12は、収容槽20内への第2熱媒体15aの循環を停止する制御を行い、処理を終了する。 In step S4, when it is determined that 3 minutes have passed (determination result Yes), the control unit 12 controls to stop the circulation of the second heat medium 15a into the storage tank 20 and ends the process.
[作用効果]
 本実施形態の処理装置10Bにおいても、第1実施形態の処理装置10と同様に、検体容器の搬送不良の問題を解消することができるとともに、処理時間を短縮することができる。
[Action effect]
Similarly to the processing device 10 of the first embodiment, the processing device 10B of the present embodiment can solve the problem of poor transport of the sample container and can shorten the processing time.
 また、本実施形態の処理装置10Bは、以上で説明したように、熱媒体供給部34から供給される熱媒体15を供給口20dに供給する供給路46と、供給路46上に配置され、供給口20dに供給される前に熱媒体15を第1温度以上に加熱することにより第1熱媒体15aに変換する第1温度調整部35と、供給路46上に配置され、供給口20dに供給される前に熱媒体15を第2温度以下に冷却することにより第2熱媒体15bに変換する第2温度調整部36と、を備える。 Further, as described above, the processing apparatus 10B of the present embodiment is arranged on the supply path 46 and the supply path 46 for supplying the heat medium 15 supplied from the heat medium supply unit 34 to the supply port 20d. A first temperature adjusting unit 35 that converts the heat medium 15 into a first heat medium 15a by heating the heat medium 15 to a first temperature or higher before being supplied to the supply port 20d, and a first temperature adjusting unit 35 arranged on the supply path 46 and connected to the supply port 20d. A second temperature adjusting unit 36 that converts the heat medium 15 into a second heat medium 15b by cooling the heat medium 15 to a second temperature or lower before being supplied is provided.
 このような構成とすることにより、熱媒体を貯留する貯留部が1つで済むため、熱媒体交換機構の容積を低減させることができ、さらに配管の構成を簡素化することができる。 With such a configuration, since only one storage unit is required to store the heat medium, the volume of the heat medium exchange mechanism can be reduced, and the piping configuration can be simplified.
[変形例]
 上記実施形態は、一例であり、以下に示すように種々の変形が可能である。
[Modification example]
The above embodiment is an example, and various modifications are possible as shown below.
 例えば、エンドトキシン測定に用いるライセート試薬としては、LAL試薬に限らず、アメリカカブトガニとは別種のカブトガニ(Tachypleus tridentatus)の血球抽出物から調製されるTAL(Tachypleus Amebocyte Lysate)試薬を用いてもよい。 For example, the lysate reagent used for endotoxin measurement is not limited to the LAL reagent, and a TAL (Tachypleus Amebocyte Lysate) reagent prepared from a blood cell extract of a horseshoe crab (Tachypleus tridentatus), which is a different species from the American horseshoe crab, may be used.
 また、エンドトキシン試験の手法としては、上記実施形態で説明した比濁法に限らず、エンドトキシンの作用によるライセート試薬のゲル形成を指標とするゲル化法、または、合成基質の加水分解による発色を指標にする比色法を用いてもよい。 The endotoxin test method is not limited to the turbidimetry method described in the above embodiment, but is a gelation method using the gel formation of a lysate reagent by the action of endotoxin as an index, or a color development by hydrolysis of a synthetic substrate as an index. You may use the colorimetric method.
 また、カブトガニ血球抽出物を含む試薬を用いた測定は、エンドトキシンに限らず、β-グルカンでもよい。 Further, the measurement using the reagent containing the horseshoe crab blood cell extract is not limited to endotoxin, but may be β-glucan.
 また、本開示の処理装置として、カブトガニ血球抽出物を含む試薬を用いた測定の前処理を行う処理装置を例に説明したが、他の試薬を用いた測定の前処理を行う処理装置に適用してもよい。 Further, as the processing apparatus of the present disclosure, a processing apparatus that performs pretreatment for measurement using a reagent containing horseshoe crab blood cell extract has been described as an example, but it is applied to a processing apparatus that performs pretreatment for measurement using other reagents. You may.
 また、検体溶液に対する前処理は、上記実施形態で説明した、10分加熱後に3分冷却する処理に限らず、検体溶液に対して行う測定に合わせて、適宜変更してもよい。 Further, the pretreatment for the sample solution is not limited to the treatment for heating for 10 minutes and then cooling for 3 minutes as described in the above embodiment, and may be appropriately changed according to the measurement performed on the sample solution.
 また、処理装置で行う検体溶液への温度調整処理は、測定に先だって行われる前処理に限らず、どのような用途であってもよい。 Further, the temperature adjustment process for the sample solution performed by the processing device is not limited to the pretreatment performed prior to the measurement, and may be used for any purpose.
 また、熱媒体は、純水に限らず、不凍液を用いてもよい。熱媒体として不凍液を用いた場合には、0℃に近い温度でも熱媒体が凍らずに熱媒体交換機構内を循環させることができるため、検体溶液の冷却をより迅速に行うことができる。また、熱媒体は、液体に限らず、流体であればどのようなものを用いてもよい。 Further, the heat medium is not limited to pure water, and antifreeze may be used. When an antifreeze solution is used as the heat medium, the heat medium can be circulated in the heat medium exchange mechanism without freezing even at a temperature close to 0 ° C., so that the sample solution can be cooled more quickly. Further, the heat medium is not limited to a liquid, and any fluid may be used.
 また、上記実施形態において、例えば、制御部11,12および測定制御部63等の各種の処理を実行する処理部(Processing Unit)のハードウェア的な構造としては、次に示す各種のプロセッサ(Processor)を用いることができる。各種のプロセッサには、ソフトウェアを実行して各種の処理部として機能する汎用的なプロセッサであるCPU(Central Processing Unit)に加えて、FPGA(Field Programmable Gate Array)等の製造後に回路構成を変更可能なプロセッサであるプログラマブルロジックデバイス(Programmable Logic Device :PLD)、および/またはASIC(Application Specific Integrated Circuit)等の特定の処理を実行させるために専用に設計された回路構成を有するプロセッサである専用電気回路等が含まれる。 Further, in the above embodiment, for example, the hardware structure of the processing unit (Processing Unit) that executes various processes such as the control units 11 and 12 and the measurement control unit 63 includes various processors (Processors) shown below. ) Can be used. For various processors, in addition to the CPU (Central Processing Unit), which is a general-purpose processor that executes software and functions as various processing units, the circuit configuration can be changed after the manufacture of FPGA (Field Programmable Gate Array), etc. A dedicated electric circuit that is a processor having a circuit configuration specially designed to execute a specific process such as a programmable logic device (PLD) and / or an ASIC (Application Specific Integrated Circuit). Etc. are included.
 1つの処理部は、これらの各種のプロセッサのうちの1つで構成されてもよいし、同種または異種の2つ以上のプロセッサの組み合わせ(例えば、複数のFPGAの組み合わせ、および/または、CPUとFPGAとの組み合わせ)で構成されてもよい。このように、各種の処理部は、ハードウェア的な構造として、上記各種のプロセッサの1つ以上を用いて構成される。 One processor may be composed of one of these various processors, or a combination of two or more processors of the same type or different types (for example, a combination of a plurality of FPGAs and / or a CPU and a CPU). It may be configured in combination with FPGA). As described above, the various processing units are configured by using one or more of the above-mentioned various processors as a hardware structure.
 さらに、これらの各種のプロセッサのハードウェア的な構造としては、より具体的には、半導体素子等の回路素子を組み合わせた電気回路(circuitry)を用いることができる。 Further, as the hardware structure of these various processors, more specifically, an electric circuit (circuitry) in which circuit elements such as semiconductor elements are combined can be used.
 なお、以上に示した記載内容および図示内容は、本開示の技術に係る部分についての詳細な説明であり、本開示の技術の一例に過ぎない。例えば、上記の構成、機能、作用、および効果に関する説明は、本開示の技術に係る部分の構成、機能、作用、および効果の一例に関する説明である。よって、本開示の技術の主旨を逸脱しない範囲内において、以上に示した記載内容および図示内容に対して、不要な部分を削除したり、新たな要素を追加したり、置き換えたりしてもよいことはいうまでもない。また、錯綜を回避し、本開示の技術に係る部分の理解を容易にするために、以上に示した記載内容および図示内容では、本開示の技術の実施を可能にする上で特に説明を要しない技術常識などに関する説明は省略されている。 The contents described and illustrated above are detailed explanations of the parts related to the technology of the present disclosure, and are merely examples of the technology of the present disclosure. For example, the above description of the configuration, function, action, and effect is an example of the configuration, function, action, and effect of a portion of the art of the present disclosure. Therefore, unnecessary parts may be deleted, new elements may be added, or replacements may be made to the described contents and illustrated contents shown above within a range that does not deviate from the gist of the technique of the present disclosure. Needless to say. In addition, in order to avoid complications and facilitate understanding of the parts relating to the technology of the present disclosure, the above-mentioned description and illustrations require special explanation in order to enable the implementation of the technology of the present disclosure. The explanation about the common technical knowledge is omitted.
 2020年1月22日に出願された日本出願特願2020-008729の開示はその全体が参照により本明細書に取り込まれる。本明細書に記載された全ての文献、特許出願、及び技術規格は、個々の文献、特許出願、及び技術規格が参照により取り込まれることが具体的かつ個々に記された場合と同程度に、本明細書中に参照により取り込まれる。 The entire disclosure of Japanese Patent Application No. 2020-008729 filed on January 22, 2020 is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards described herein are to the same extent as if the individual documents, patent applications, and technical standards were specifically and individually stated to be incorporated by reference. Incorporated herein by reference.

Claims (12)

  1.  検体容器を収容し、かつ、前記検体容器内の検体溶液の温度を変化させるための流体状の熱媒体を前記検体容器の周囲に貯留することが可能な収容槽と、
     前記収容槽内の熱媒体を交換する熱媒体交換機構であって、前記検体容器内の検体溶液を第1温度に加熱するための第1熱媒体と、前記第1温度よりも低い第2温度に前記検体溶液を冷却するための第2熱媒体とを交換する熱媒体交換機構と、を備える処理装置。
    A storage tank that accommodates the sample container and can store a fluid heat medium for changing the temperature of the sample solution in the sample container around the sample container.
    A heat medium exchange mechanism for exchanging the heat medium in the storage tank, the first heat medium for heating the sample solution in the sample container to the first temperature, and the second temperature lower than the first temperature. A processing apparatus including a heat medium exchange mechanism for exchanging a second heat medium for cooling the sample solution.
  2.  前記収容槽には、前記熱媒体を供給する供給口と、前記熱媒体を排出する排出口とが設けられており、
     前記熱媒体交換機構は、前記供給口と前記排出口とに接続された配管を通じて、前記収容槽内の前記第1熱媒体または前記第2熱媒体を循環させる
     請求項1に記載の処理装置。
    The storage tank is provided with a supply port for supplying the heat medium and a discharge port for discharging the heat medium.
    The processing apparatus according to claim 1, wherein the heat medium exchange mechanism circulates the first heat medium or the second heat medium in the storage tank through a pipe connected to the supply port and the discharge port.
  3.  前記第1熱媒体を供給する第1熱媒体供給部に接続される第1供給路と、
     前記第2熱媒体を供給する第2熱媒体供給部に接続される第2供給路と、
     前記第1供給路と前記供給口を連通させる第1状態と、前記第2供給路と前記供給口を連通させる第2状態とを切り替える弁と、を備える
     請求項2に記載の処理装置。
    A first supply path connected to the first heat medium supply unit that supplies the first heat medium, and
    A second supply path connected to the second heat medium supply unit that supplies the second heat medium, and
    The processing apparatus according to claim 2, further comprising a first state for communicating the first supply path and the supply port, and a valve for switching between the second state for communicating the second supply path and the supply port.
  4.  熱媒体供給部から供給される前記熱媒体を前記供給口に供給する供給路と、
     前記供給路上に配置され、前記供給口に供給される前に前記熱媒体を前記第1温度以上に加熱することにより前記第1熱媒体に変換する第1温度調整部と、
     前記供給路上に配置され、前記供給口に供給される前に前記熱媒体を前記第2温度以下に冷却することにより前記第2熱媒体に変換する第2温度調整部と、を備える
     請求項2に記載の処理装置。
    A supply path for supplying the heat medium supplied from the heat medium supply unit to the supply port, and
    A first temperature adjusting unit which is arranged on the supply path and converts the heat medium into the first heat medium by heating the heat medium to the first temperature or higher before being supplied to the supply port.
    2. Claim 2 comprising a second temperature adjusting unit which is arranged on the supply path and converts the heat medium into the second heat medium by cooling the heat medium to the second temperature or lower before being supplied to the supply port. The processing apparatus described in.
  5.  前記熱媒体は、液体である
     請求項1から4のいずれか1項に記載の処理装置。
    The processing apparatus according to any one of claims 1 to 4, wherein the heat medium is a liquid.
  6.  前記収容槽に前記第1熱媒体が供給されてから予め設定された設定時間が経過した後、前記熱媒体交換機構を制御することにより、前記収容槽に前記第2熱媒体を供給させる制御部を備える
     請求項1から5のいずれか1項に記載の処理装置。
    A control unit that supplies the second heat medium to the storage tank by controlling the heat medium exchange mechanism after a preset set time has elapsed since the first heat medium was supplied to the storage tank. The processing apparatus according to any one of claims 1 to 5.
  7.  前記熱媒体を前記第1熱媒体とするために加熱するヒーターを備え、
     前記ヒーターの温度は、30℃以上80℃以下である
     請求項1から6のいずれか1項に記載の処理装置。
    A heater for heating the heat medium to be the first heat medium is provided.
    The processing apparatus according to any one of claims 1 to 6, wherein the temperature of the heater is 30 ° C. or higher and 80 ° C. or lower.
  8.  前記ヒーターの温度は、60℃以上80℃以下である
     請求項7項に記載の処理装置。
    The processing apparatus according to claim 7, wherein the temperature of the heater is 60 ° C. or higher and 80 ° C. or lower.
  9.  前記熱媒体を前記第2熱媒体とするために冷却する冷却素子を備え、
     前記冷却素子の温度は、0℃以上10℃以下である
     請求項1から8のいずれか1項に記載の処理装置。
    A cooling element for cooling the heat medium to serve as the second heat medium is provided.
    The processing apparatus according to any one of claims 1 to 8, wherein the temperature of the cooling element is 0 ° C. or higher and 10 ° C. or lower.
  10.  前記収容槽は、複数の前記検体容器を収容する構成とされている
     請求項1から9のいずれか1項に記載の処理装置。
    The processing apparatus according to any one of claims 1 to 9, wherein the storage tank is configured to store a plurality of the sample containers.
  11.  前記検体溶液は、カブトガニ血球抽出物を含む試薬を用いた測定の測定対象であり、
     前記熱媒体交換機構によって前記検体溶液の温度を変化させる処理は、前記測定を実行する前に行われる前処理である
     請求項1から10のいずれか1項に記載の処理装置。
    The sample solution is a measurement target for measurement using a reagent containing horseshoe crab blood cell extract.
    The processing apparatus according to any one of claims 1 to 10, wherein the processing for changing the temperature of the sample solution by the heat medium exchange mechanism is a pretreatment performed before performing the measurement.
  12.  請求項1から11のいずれか1項に記載の処理装置と、
     前記検体溶液に対する測定を行う測定装置と、を備える測定システム。
    The processing apparatus according to any one of claims 1 to 11.
    A measurement system including a measuring device for measuring the sample solution.
PCT/JP2020/049204 2020-01-22 2020-12-28 Processing device and measurement system WO2021149465A1 (en)

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