JP7394885B2 - Processing equipment and measurement systems - Google Patents

Description

The present disclosure relates to processing devices and measurement systems.

BACKGROUND ART In order to analyze specimens such as biological samples, various substances contained in the specimens 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 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 biological reactions such as fever when even a trace amount enters the bloodstream. Specimens include biological samples such as blood, as well as pharmaceuticals (for example, injections) that are directly introduced into a living body. When performing measurements using such lysate reagents, pretreatment such as heating and cooling the sample solution may be performed prior to the measurement, and processing equipment that performs such pretreatment is not known. It is being

JP-A-2017-129429 describes a measuring device that measures the amount of endotoxin in a sample solution using a LAL (Limulus Amebocyte Lysate) reagent as a lysate reagent. Furthermore, Japanese Patent Application Laid-Open No. 08-029432 describes a processing device that pre-processes a sample solution.

The processing apparatus described in Japanese Patent Application Laid-Open No. 08-029432 includes a transport mechanism that transports a sample container from a heating section to a cooling section using a handling robot. In this transport mechanism, a handling robot grips a sample container inserted into a container insertion hole of a heating section, moves an arm of the robot upward, and pulls out the sample container from the container insertion hole. Next, the handling robot transports the specimen container to the upper part of the cooling section, moves the arm of the robot downward, and inserts the specimen container into the container insertion hole of the cooling section.

However, when a specimen container is transported by a handling robot as in the transport mechanism of JP-A-08-029432, the specimen container gripped by the handling robot tilts during transport and cannot be inserted into the container insertion hole of the cooling section. There is a possibility that a transportation defect such as running out may occur. Furthermore, when the handling robot transports the sample containers one by one, there is a problem that if there are many sample containers, the transport efficiency is poor and the processing time becomes long.

In view of the above circumstances, the technology of the present disclosure is capable of suppressing transport failures when transporting sample containers from the heating section to the cooling section, and suppressing prolongation of processing time caused by transporting the sample containers. The object of the present invention is to provide a possible processing device and a measuring system equipped with this processing device.

A processing device according to one aspect of the present disclosure includes a housing capable of accommodating a sample container and storing a fluid heat medium around the sample container for changing the temperature of a sample solution in the sample container. A heat medium exchange mechanism for exchanging a heat medium in the storage tank, the first heat medium for heating the sample solution in the sample container to a first temperature, and a second temperature lower than the first temperature. and a heat medium exchange mechanism for exchanging the sample solution with a second heat medium for cooling the sample solution.

In the processing apparatus of the above aspect, the storage tank is provided with a supply port for supplying the 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 within the storage tank may be circulated through the piping.

Moreover, in the processing apparatus of the above aspect, the first supply path is connected to the first heat medium supply section that supplies the first heat medium, and the first supply path is connected to the second heat medium supply section that supplies the second heat medium. It may also include a second supply path and a valve that switches between a first state in which the first supply path and the supply port communicate with each other and a second state in which the second supply path and the supply port communicate with each other.

In addition, in the processing apparatus of the above aspect, there is provided a supply path for supplying the heat medium supplied from the heat medium supply unit to the supply port, and a supply path that is arranged on the supply path and heats the heat medium to a first temperature before being supplied to the supply port. A first temperature adjustment section that converts the heat medium into a first heat medium by heating the heat medium to a temperature higher than that of the second heat medium; It may also include a second temperature adjustment section that converts the temperature into .

Moreover, in the processing apparatus of the above aspect, the heat medium may be a liquid.

Further, in the processing apparatus of the above aspect, after a preset time has elapsed since the first heat medium is supplied to the storage tank, the second heat medium is supplied to the storage tank by controlling the heat medium exchange mechanism. It may also include a control unit that supplies the medium.

Moreover, the processing apparatus of the above aspect may include a heater for heating the heat medium as the first heat medium, and the temperature of the heater may be 30° C. or more and 80° C. or less. Note that the temperature of the heater may be 60° C. or higher and 80° C. or lower.

Further, the processing apparatus of the above aspect may include a cooling element for cooling the heat medium as the second heat medium, and the temperature of the cooling element may be 0° C. or more and 10° C. or less.

Moreover, in the processing apparatus of the above aspect, the storage tank may be configured to accommodate a plurality of sample containers.

In addition, in the processing apparatus of the above aspect, the specimen solution is a measurement target of a measurement using a reagent containing a horseshoe crab blood cell extract, and the process of changing the temperature of the specimen solution by the heat medium exchange mechanism is performed to perform the above measurement. It may also be a pretreatment performed before the treatment.

A measurement system according to one aspect of the present disclosure includes the processing device described above and a measurement device that performs measurement on a sample solution.

According to the technology of the present disclosure, a process that can suppress transport defects when transporting a sample container from a heating section to a cooling section and suppress an increase in processing time caused by transporting the sample container A device and a measurement system comprising this processing device can be provided.

FIG. 1 is a diagram showing an overview of a measurement system. It is a graph showing the transition of temperature change of the specimen solution during pretreatment. FIG. 1 is a schematic diagram showing the configuration of a processing device according to a first embodiment. It is a perspective view of a storage tank. It is an exploded perspective view of a storage tank. It is a sectional view of a storage tank. FIG. 1 is a schematic diagram showing the configuration of a measuring device. It is a flowchart for explaining the flow of preprocessing in the processing device. It is a figure showing the state at the time of heating in a processing device. It is a figure showing the state at the time of cooling in a processing device. FIG. 2 is a schematic diagram showing the configuration of a processing device according to a second embodiment. FIG. 3 is a cross-sectional view showing the structure around the first temperature adjustment section and the second temperature adjustment section.

"First embodiment"
[Overall configuration of measurement system]
FIG. 1 is a diagram showing an overview of a measurement system 1 including a processing device 10 according to a first embodiment of the present disclosure. As shown in FIG. 1, the measurement system 1 includes a processing device 10 and a measurement device 60. The processing device 10 performs pretreatment on a sample solution C, which is generated by diluting a sample A, such as a biological sample, by adding a buffer B to the sample A, which is performed before performing endotoxin measurement. The measurement device 60 performs endotoxin measurement using the pretreated sample solution C as a measurement target.

As mentioned above, endotoxin is a typical pyrogen that causes biological reactions such as fever when it enters the blood, even in minute amounts.Specimen A is a biological sample such as blood that is directly introduced into the body. Pharmaceutical products (for example, injections, etc.). In the endotoxin measurement, the amount of endotoxin in sample solution C is measured, and the endotoxin in sample A is quantified. Endotoxin measurement is a measurement using a reagent such as lysate reagent D containing a horseshoe crab blood cell extract. Endotoxin measurement is a measurement that utilizes the fact that endotoxin causes aggregation and coagulation of horseshoe crab blood cell extract. In endotoxin measurement, first, lysate reagent D containing a horseshoe crab blood cell extract is added to sample solution C. A sample solution E is generated by stirring the sample solution C to which the lysate reagent D has been added. Next, the amount of endotoxin in the sample solution E is measured based on the change in the properties of the sample solution E.

A lysate reagent prepared from a hemocyte extract of the American horseshoe crab (Limulus polyphemus), which is a horseshoe crab that serves as a raw material for lysate reagent D, is called LAL (Limulus Amebocyte Lysate) reagent.

The measuring device 60 in the measuring system 1 of this embodiment uses LAL reagent as the lysate reagent D, and uses the turbidity change of the sample solution E as an index in the process of gelling the lysate reagent D by reaction with endotoxin. Measure endotoxin using the turbidity method. When measuring endotoxin by turbidimetry, pretreatment of heating and cooling the sample solution C is required prior to measurement. As shown in FIG. 1, pretreatment is performed on sample solution C, and endotoxin measurement is performed on sample solution E containing pretreated sample solution C and lysate reagent D.

Specifically, as shown in the graph of FIG. 2, the pretreatment when measuring endotoxin by turbidimetry involves first diluting sample A by adding buffer B to dilute the sample solution C. Heat treatment is performed to inactivate interfering factors in endotoxin measurement by heating at a temperature of 70° C. for about 10 minutes. Thereafter, a cooling process is performed to stop the inactivation process by cooling the sample solution C at about 70° to a temperature of about 5°C. The cooling process time from the start of cooling to the end of cooling is, for example, about 3 minutes. In the cooling process, if it takes time to cool the sample solution C at about 70 degrees to a temperature of about 5 degrees Celsius, variations will occur in the time for the inactivation process on the sample solution C, and the accuracy of endotoxin measurement will decrease. Therefore, in the pretreatment, it is necessary to rapidly cool the specimen solution C, specifically, to cool the specimen solution C at about 70° to a temperature of about 5° C. in a short period of time.

The processing device 10 in the measurement system 1 of the present embodiment is a device that performs the above-mentioned pretreatment on a sample solution C obtained by adding buffer B to diluted sample A.

<Processing device>
FIG. 3 is a schematic diagram 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 accommodate the sample container 5 and store a 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 storage tank 20. The control unit 11 controls the heat medium exchange mechanism. The sample container 5 loaded into the processing device 10 has, for example, a cylindrical appearance and includes a main body 5a and a lid 5b. For example, pure water is used as the fluid heat medium 15 stored in the storage tank 20.

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 (a cross-sectional view taken along the line VI-VI in FIG. 4). Note that in FIG. 6, the specimen container 5 is shown in a side view rather than a cross-sectional view. As shown in FIG. 4, a plurality of container insertion holes 20b for inserting sample containers 5 are formed in 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 storage tank 20 is provided on the other side surface 20e in the longitudinal direction.

The storage tank 20 includes a tank-shaped container main body 21 with an open top, a holding member 22 that holds the sample container 5, a lid 23 that seals the opening of the container main body 21, and a piping installation on the side of the supply port 20d. It includes a fitting 24 and a fitting 25 for fitting piping on the side of the discharge port 20f.

In the container 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 this embodiment, the container body 21 is made of polyphthalamide. The container body 21 is preferably made of a resin material, such as polyphthalamide (PPA) or polyphenylene ether (PPE), which has high heat resistance and heat insulation properties, high chemical resistance to heat media, and low heat capacity.

The holding member 22 has a shape in which a flat pedestal portion 22a and a plurality of cylindrical 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 this 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.

The lid body 23 is formed with insertion openings 23a for a plurality of container insertion holes 20b. When the storage tank 20 is assembled, the insertion port 23a of the lid body 23 and the inside of the container insertion portion 22b of the holding member 22 communicate with each other to form a container insertion hole 20b. In this embodiment, the lid body 23 is made of polyphthalamide similarly to the container body 21. The lid body 23 is preferably made of a resin material such as polyphthalamide (PPA) or polyphenylene ether (PPE), which has high heat resistance and heat insulation properties, high chemical resistance to heat media, and further has a small heat capacity. .

The inner diameter of the container insertion hole 20b is slightly larger than the outer diameter of the sample container 5, but is approximately the same diameter. Therefore, when the sample container 5 is inserted into the container insertion hole 20b, the sample container 5 is held within the container insertion hole 20b without tilting.

In the storage tank 20 of the processing apparatus 10 of this embodiment, ten container insertion holes 20b are arranged in a line. The processing device 10 can be loaded with up to ten specimen containers 5 and can perform pretreatment at the same time.

The pipe attachment fitting 24 includes a fitting main body 24a in which a pipe attachment portion and a bolt connection portion are formed, and a bolt 24b. The pipe mounting fitting 24 is constructed by inserting the bolt joint part of the fitting main body 24a into the supply port 20d from the outside of the container main body 21, and connecting the bolt 24b to the fitting main body 24a from the inside of the container main body 21. It is attached to the container body 21. The pipe fitting 24 has a through hole, and when the pipe fitting 24 is attached to the container body 21, the through hole of the pipe fitting 24 functions as the supply port 20d (see FIG. 6 as well). reference).

Similarly, the pipe attachment fitting 25 includes a fitting main body 25a in which a pipe attachment portion and a bolt connection portion are formed, and a bolt 25b. The pipe mounting fitting 25 is constructed by inserting the bolt joint part of the fitting main body 25a into the discharge port 20f from the outside of the container main body 21, and by connecting the bolt 25b to the fitting main body 25a from the inside of the container main body 21. It is attached to the container body 21. The pipe fitting 25 has a through hole, and when the pipe fitting 25 is attached to the container body 21, the through hole of the pipe fitting 25 functions as the discharge port 20f (see FIG. 6 as well). reference).

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 is equipped with 45. The storage tank 20, the first heat medium supply section 30, the first supply path 40, and the first discharge path 44 constitute a circulation path for the first heat medium 15a. The first heat medium supply section 30 supplies the first heat medium 15a to the storage tank 20 through the first supply path 40. The first heat medium 15a heats the sample solution C contained in the sample container 5 in the storage tank 20 to a first temperature. The first heat medium 15a supplied to the storage tank 20 is discharged from the storage tank 20 through the first discharge path 44, and is recovered to the first heat medium supply section 30 through the first discharge path 44.

The storage tank 20, the second heat medium supply section 31, the second supply path 41, and the second discharge path 45 constitute a circulation path for the second heat medium 15b. The second heat medium supply unit 31 supplies the second heat medium 15b to the storage tank 20 through the second supply path 41. The second heat medium 15b cools the sample solution C contained 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 path 45, and is recovered to the second heat medium supply section 31 through the second discharge path 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 passage 44 and the discharge port 20f communicate with each other and a second state in which the second discharge passage 45 and the discharge port 20f communicate with each other.

The first heat medium supply section 30 includes a storage section 30a that stores the heat medium 15a, a heater 30b that heats the heat medium 15 stored in the storage section 30a to use it as the first heat medium 15a, and a pump 30d. , a pipe 30c connecting the discharge port of the storage section 30a and the supply port of the pump 30d.

As a pretreatment for the specimen solution C when measuring endotoxin by turbidimetry, it is preferable to heat it at a temperature of 30° C. or higher and 80° C. or lower. Therefore, the temperature of the heater 30b can be set to 30°C or more and 80°C or less. Note that the temperature of the heater 30b is more preferably 60°C or more and 80°C or less. In this embodiment, the temperature of the heater 30b is set to 70° C. (an example of the first temperature) based on control from the control unit 11.

The first supply path 40 is constituted by piping that connects the discharge port of the pump 30d and the connection port 32a of the valve 32.

The first discharge path 44 is configured by piping that connects the connection port 33a of the valve 33 and the supply port of the first heat medium supply section 30.

The second heat medium supply section 31 includes a storage section 31a that stores the heat medium 15, a cooling element 31b that cools the heat medium 15 stored in the storage section 31a as a second heat medium 15b, and a pump 31d. and a pipe 31c connecting the discharge port of the storage section 31a and the supply port of the pump 31d.

As a pretreatment for the specimen solution C when measuring endotoxin by turbidimetry, it is preferable to cool it at a temperature of 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 this 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. A Peltier element is used as the cooling element 31b.

The second supply path 41 is constituted by piping that connects the discharge port of the pump 31d and the connection port 32b of the valve 32.

The second discharge path 45 is constituted by piping that connects the connection port 33b of the valve 33 and the supply port of the second heat medium supply section 31.

The valve 32 is a three-way valve, and includes a connection port 32a to which the first supply path 40 is connected, a connection port 32b to which the second supply path 41 is connected, and a common supply path that connects the valve 32 and the supply port 20d. 42 is connected to the connection port 32c. The valve 32 can be switched 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 control from the control unit 11. It is composed of In the first state, the connection port 32a and the connection port 32c communicate internally. In the second state, the connection port 32b and the connection port 32c communicate internally. The common supply path 42 is constituted by piping that connects the connection port 32c and the supply port 20d.

The valve 33 is a three-way valve, and includes a connection port 33a to which the first discharge path 44 is connected, a connection port 33b to which the second discharge path 45 is connected, and a common discharge path that connects the valve 33 and the discharge port 20f. 43 is connected to the connection port 33c. The valve 33 can be switched 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 channel 45 and the discharge port 20f communicate with each other based on control from the control unit 11. It is composed of In the first state, the connection port 33a and the connection port 33c communicate internally. In the second state, the connection port 33b and the connection port 33c communicate internally. The common discharge path 43 is constituted by piping that connects 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 when the CPU 11a executes a control program, and is, for example, a volatile memory. The storage 11c is a nonvolatile memory for storing various data, and a flash memory or the like is used. The control section 11 functions as a control section that controls each section of the heater 30b, pump 30d, cooling element 31b, pump 31d, valve 32, and valve 33 by executing a control program.

<Measuring device>
FIG. 7 is a schematic diagram 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 measurement light onto the sample container 5, and a PD (Photodiode) disposed at a position facing the LED 61 with the sample container 5 in between. ) 62 and a measurement control section 63. The measurement control unit 63 measures the amount of endotoxin in the sample solution E based on the detection result of the PD 62. Further, the measurement control unit 63 controls the LED 61 and the PD 62. The specimen container 5 contains a specimen solution E in which a pretreated specimen solution C and a lysate reagent D are mixed.

The measurement control section 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 when the CPU 63a executes a measurement control program, and is, for example, a volatile memory. The storage 63c is a nonvolatile memory for storing various data, and a flash memory or the like is used. The measurement control section 63 functions as a control section that controls each section of the LED 61 and the PD 62 by executing a measurement control program. Furthermore, 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 the PD 62 by executing a measurement control program.

As a method for measuring endotoxin in the measuring device 60, the nephelometric method is used as described above. The nephelometric method is a method that uses as an index the change in turbidity during the gelation process of lysate reagent D due to the action of endotoxin. The turbidity of the sample solution E changes depending on the amount of endotoxin in the sample solution E and the elapsed time since the lysate reagent D was added to the pretreated sample solution C. When the turbidity of the sample solution E changes, the amount of measurement light that passes through the sample solution E changes. Therefore, by measuring the change in the amount of transmitted light over time using the PD62, the state and transition of the turbidity of the sample solution E can be measured. 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.

[Flow of preprocessing]
FIG. 8 is a flowchart for explaining the flow of preprocessing in the processing device 10.

First, sample solution C is generated by adding buffer 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 circulating 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 are communicated. Further, the valve 33 is controlled to be switched to a first state in which the first discharge path 44 and the discharge port 20f are communicated with each other. Next, the control unit 11 drives the pump 30d, and as shown by the arrow in FIG. 44 to control circulation within the storage tank 20.

Next, the control unit 11 determines whether 10 minutes have passed since the start of circulation of the first heat medium 15a into the storage tank 20 (step S2). In step S2, if it is determined that 10 minutes have not elapsed (determination result No), the control unit 11 continues circulating the first heat medium 15a into the storage tank 20.

In step S2, if it is determined that 10 minutes have elapsed (determination result: Yes), the control unit 11 stops the circulation of the first heat medium 15a into the storage tank 20, and transfers the second heat medium 15b into the storage tank. 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 are communicated. Further, the valve 33 is controlled to be switched to a second state in which the second discharge path 45 and the discharge port 20f are communicated with each other. Next, the control unit 11 drives the pump 31d, and as shown by the arrow in FIG. 45 to control circulation within the storage tank 20.

Next, the control unit 11 determines whether three minutes have passed since the start of circulation of the second heat medium 15b into the storage tank 20 (step S4). In step S4, if it is determined that three minutes have not elapsed (determination result No), the control unit 11 continues circulating the second heat medium 15b into the storage tank 20.

In step S4, if it is determined that three minutes have elapsed (determination result: Yes), the control unit 11 performs control to stop the circulation of the second heat medium 15a into the storage tank 20, and ends the process.

[Effect]
As described above, the processing apparatus 10 of this embodiment accommodates the sample container 5 and transfers the fluid heat medium 15 to the sample container 5 for changing the temperature of the sample solution C in the sample container 5. A storage tank 20 that can be stored around the storage tank 20 and a heat medium exchange mechanism that exchanges the heat medium 15 in the storage tank 20, and is for heating the sample solution C in the sample container 5 to a first temperature. It includes a heat medium exchange mechanism that exchanges the first heat medium 15a and the second heat medium 15b for cooling the sample solution C to a second temperature lower than the first temperature.

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 for a transport mechanism such as a handling robot to transport sample containers from the heating section to the cooling section, unlike conventional processing equipment that has separate heating and cooling sections. The problem of poor conveyance can be solved.

Moreover, even when a plurality of sample containers 5 are loaded into the storage tank 20, both heating and cooling can be performed without moving the plurality of sample containers 5. Therefore, processing time can be shortened compared to the case where sample containers are transported one by one by a handling robot as in conventional processing apparatuses.

In addition, in the processing apparatus 10 of this 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 The first heat medium 15a or the second heat medium 15b in the storage tank 20 is configured to be circulated through piping connected to the supply port 20d and the discharge port 20f.

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 the set temperature. Therefore, compared to the case where the first heat medium 15a or the second heat medium 15b is not circulated, it is easier to perform heating or cooling quickly.

Furthermore, the processing apparatus 10 of the present embodiment includes a first supply path connected to the first heat medium supply section 30 that supplies the first heat medium 15a, and a second heat medium supply section that supplies the second heat medium 15b. 31, a valve 32 that switches between a first state in which the first supply channel and the supply port 20d communicate with each other, and a second state in which the second supply channel and the supply port 20d communicate with each other. .

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, which have different temperatures. By distinguishing the supply paths, the first heat medium supply section 30 and the second heat medium supply section 31 can be provided separately, as shown in this example. Therefore, since the first heat medium 15a and the second heat medium 15b are separately prepared and either one is selectively supplied into the storage tank 20, the first heat medium 15a or the second heat medium 15a having a stable temperature is A heat medium 15b can be supplied.

Further, when a liquid having a higher specific heat than gas is used as the heat medium 15, the following effects can be obtained. The larger the specific heat of the heat medium 15, the harder it is to warm up and the harder it is to cool down. When heating the sample solution C, it is better to heat the sample solution C using the heat medium 15 with a large specific heat (that is, it is difficult to cool down) than to use the heat medium 15 that has a relatively small specific heat (that is, it is easy to cool down). Since the heating medium 15 is maintained in a heated state, the sample solution C can be quickly heated. When cooling the sample solution C, if a heat medium 15 with a large specific heat (i.e., does not warm easily) is used, compared to a case where a heat medium 15 with a relatively small specific heat (i.e., heats easily) is used, the heat medium 15 Since the sample solution C is maintained in a cooled state, the sample solution C can be quickly cooled.

Further, in the processing apparatus 10 of this embodiment, pure water is used as the heat medium 15. Pure water has few impurities and is less likely to corrode, so in addition to the above effects, it also contributes to preventing clogging of the pipes of the heat medium exchange mechanism.

Further, after a preset time has elapsed since the first heat medium 15a was supplied to the storage tank 20, the second heat medium 15b is supplied to the storage tank 20 by controlling the heat medium exchange mechanism. By providing the section 11, preprocessing can be automated.

Furthermore, a heater 30b for heating the heat medium 15 as the first heat medium 15a is provided, and by setting the temperature of this heater 30b to 30° C. or more and 80° C. or less, pretreatment for endotoxin measurement by turbidimetry is performed. A suitable heat treatment can be performed. Note that the heat treatment can be performed more efficiently by setting the temperature of the heater 30b to 60° C. or higher and 80° C. or lower.

Furthermore, a cooling element 31b is provided to cool the heat medium 15 as a second heat medium 15b, and by setting the temperature of this cooling element 31b to 0°C or more and 10°C or less, it is possible to Cooling treatment suitable for pretreatment can be performed.

“Second embodiment”
In the measurement system 1, the processing device 10 can be changed to a processing device 10B according to the second embodiment. Note that the configurations other than the processing device 10B are the same as those in the first embodiment, and therefore the description of the components other than the processing device 10B will be omitted.

<Processing device>
FIG. 11 is a schematic diagram showing the configuration of a processing device 10B according to the second embodiment. As shown in FIG. 11, the processing device 10B has a housing capable of accommodating the specimen container 5 and storing a fluid heat medium 15 for changing the temperature of the specimen solution C in the specimen container 5. It includes a tank 20, a heat medium exchange mechanism that exchanges the heat medium in the storage tank 20, and a control unit 12 that controls the heat medium exchange mechanism.

The storage tank 20 is the same as the processing apparatus 10 according to the first embodiment, so a description thereof will be omitted.

The heat medium exchange mechanism is arranged on the heat medium supply section 34, a supply path 46 that supplies the heat medium 15 supplied from the heat medium supply section 34 to the supply port 20d of the storage tank 20, and is arranged on the supply path 46, and A first temperature adjustment section 35 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; A second temperature adjustment section 36 converts the heat medium 15 to a second heat medium 15b by cooling the heat medium 15 to a second temperature or lower before the heat transfer is carried out; and a discharge path 47 for returning.

The heat medium supply section 34 includes a storage section 34a that stores the heat medium 15, a pump 34c, and a pipe 34b that connects the discharge port of the storage section 34a and the supply port of the pump 34c.

The supply path 46 is constituted by piping that connects the discharge port of the pump 34c and the supply port 20d of the storage tank 20.

The first temperature adjustment section 35 includes a heater. As a pretreatment for the specimen solution C when measuring endotoxin by turbidimetry, it is preferable to heat it at 60°C or higher and 80°C or lower. In this embodiment, the temperature of the first heat medium 15a is set to 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 attachment position of the first temperature adjustment unit 35 in the supply path 46 is 70°C.

The second temperature adjustment section 36 includes a Peltier element that is a cooling element. As a pretreatment for the specimen solution C when measuring endotoxin by turbidimetry, it is preferable to cool it at a temperature of 0° C. or higher and 10° C. or lower. In this embodiment, the temperature of the second heat medium 15b is 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 attachment position of the second temperature adjustment unit 36 in the supply path 46 is 5°C.

The discharge path 47 is constituted by a pipe that connects the discharge port 20f of the storage tank 20 and the supply port of the storage section 34a.

FIG. 12 is a cross-sectional view showing the structure around the first temperature adjustment section 35 and the second temperature adjustment section 36. As shown in FIG. As shown in FIG. 12, the first temperature adjustment section 35 is attached in close contact with the supply path 46, and instantly controls the heat medium 15 passing through the installation position of the first temperature adjustment section 35 in the supply path 46. is converted into the first heat medium 15a. The cross-sectional shape of the supply path 46 is, for example, a flat shape with a thinner thickness in a direction parallel to the plane of the paper and a longer depth in a direction perpendicular to the plane of the paper relative to the thickness. The first temperature adjustment section 35 extends in the depth direction of the supply path 46 so that the contact area with the supply path 46 is increased. Therefore, since the amount of the heat medium 15 passing through the attachment position of the first temperature adjustment section 35 per unit time is small, the heat medium 15 can be instantaneously heated.

Also, like the first temperature adjustment section 35, the second temperature adjustment section 36 instantly converts the heat medium 15 passing through the attachment position of the second temperature adjustment section 36 in the supply path 46 into the second heat medium 15b. . Like the first temperature adjustment section 35, the second temperature adjustment section 36 is also attached in close contact with the supply path 46, and is arranged in the depth direction of the supply path 46 so that the contact area with the supply path 46 is increased. It is extending. Thereby, since the amount of the heat medium 15 passing through the attachment position of the second temperature adjustment section 36 per unit time is small, the heat medium 15 can be instantly cooled.

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 section 12 functions as a control section that controls each section of the pump 34c, the first temperature adjustment section 35, and the second temperature adjustment section 36 by executing a control program.

[Flow of preprocessing]
FIG. 8 (common to the first embodiment) is a flowchart for explaining the flow of preprocessing in the processing device 10B.

After the sample container 5 containing the sample solution C generated by diluting the sample A by adding buffer B is inserted into the container insertion hole 20b of the storage tank 20, the control unit 12 controls the first heat medium. 15a is circulated into the storage tank 20 (step S1). Specifically, the control unit 12 drives the pump 34c and the first temperature adjustment 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. Thus, the first heat medium 15a is controlled to be circulated within the storage tank 20.

Next, the control unit 12 determines whether 10 minutes have passed since the start of circulation of the first heat medium 15a into the storage tank 20 (step S2). In step S2, if it is determined that 10 minutes have not elapsed (determination result No), the control unit 12 continues to circulate the first heat medium 15a into the storage tank 20.

In step S2, if it is determined 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 transfers the second heat medium 15b into the storage tank. 20 (step S3). Specifically, the control unit 12 stops driving the first temperature adjustment unit 35 while driving the pump 34c, and also drives the second temperature adjustment unit 36 to reduce the heat medium 15 passing through the supply path 46. The second heat medium 15b is converted into a second heat medium 15b, and the second heat medium 15b is controlled to be circulated within the storage tank 20 as shown by the arrow in FIG.

Next, the control unit 12 determines whether three minutes have passed since the start of circulation of the second heat medium 15b into the storage tank 20 (step S4). In step S4, if it is determined that three minutes have not elapsed (determination result No), the control unit 12 continues to circulate the second heat medium 15b into the storage tank 20.

In step S4, if it is determined that three minutes have elapsed (determination result: Yes), the control unit 12 performs control to stop the circulation of the second heat medium 15a into the storage tank 20, and ends the process.

[Effect]
Similarly to the processing apparatus 10 of the first embodiment, the processing apparatus 10B of the present embodiment can solve the problem of poor transportation of sample containers, and can shorten the processing time.

Furthermore, as described above, the processing device 10B of the present embodiment is arranged on the supply path 46 that supplies the heat medium 15 supplied from the heat medium supply unit 34 to the supply port 20d, and on the supply path 46, A first temperature adjustment unit 35 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; A second temperature adjustment unit 36 is provided 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.

With such a configuration, only one storage section for storing the heat medium is required, so that the volume of the heat medium exchange mechanism can be reduced, and furthermore, the configuration of the piping can be simplified.

[Modified example]
The above embodiment is an example, and various modifications are possible as shown below.

For example, the lysate reagent used for measuring endotoxin is not limited to the LAL reagent, but may also be a TAL (Tachypleus Amebocyte Lysate) reagent prepared from a blood cell extract of horseshoe crab (Tachypleus tridentatus), which is a different species from the American horseshoe crab.

In addition, methods for endotoxin testing are not limited to the turbidimetric method described in the above embodiment, but also a gelation method that uses gel formation of a lysate reagent as an indicator due to the action of endotoxin, or color development due to hydrolysis of a synthetic substrate as an indicator. A colorimetric method may also be used.

Furthermore, measurement using a reagent containing a horseshoe crab blood cell extract is not limited to endotoxin, but may also be performed on β-glucan.

In addition, as an example of the processing device of the present disclosure, a processing device that performs preprocessing for measurement using a reagent containing a horseshoe crab blood cell extract has been described as an example, but it can also be applied to a processing device that performs preprocessing for measurement using other reagents. You may.

Further, the pretreatment for the sample solution is not limited to the process of heating for 10 minutes and then cooling for 3 minutes as described in the above embodiment, but may be changed as appropriate depending on the measurement to be performed on the sample solution.

Furthermore, the temperature adjustment process performed on the sample solution by the processing device is not limited to pretreatment performed prior to measurement, and may be used for any purpose.

Furthermore, the heat medium is not limited to pure water, and antifreeze may also be used. When antifreeze is used as the heat medium, the heat medium can be circulated within the heat medium exchange mechanism without freezing even at temperatures close to 0° C., so the sample solution can be cooled more quickly. Further, the heat medium is not limited to liquid, and any fluid may be used.

In the above embodiment, for example, the hardware structure of a processing unit that executes various processes such as the control units 11 and 12 and the measurement control unit 63 includes the following various processors. ) can be used. Various processors include CPUs (Central Processing Units), which are general-purpose processors that execute software and function as various processing units, as well as FPGAs (Field Programmable Gate Arrays), whose circuit configurations can be changed after manufacturing. A programmable logic device (PLD), which is a processor, and/or a dedicated electric circuit, which is a processor with a circuit configuration specifically designed to execute a specific process, such as an ASIC (Application Specific Integrated Circuit). etc. are included.

One processing unit 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 multiple FPGAs and/or a CPU and (in combination with FPGA). In this way, various processing units are configured using one or more of the various processors described above as a hardware structure.

Furthermore, as the hardware structure of these various processors, more specifically, an electric circuit (circuitry) that is a combination of circuit elements such as semiconductor elements can be used.

Note that the descriptions and illustrations described above are detailed explanations of portions related to the technology of the present disclosure, and are merely examples of the technology of the present disclosure. For example, the above description regarding the configuration, function, operation, and effect is an example of the configuration, function, operation, and effect of the part related to the technology of the present disclosure. Therefore, unnecessary parts may be deleted, new elements may be added, or replacements may be made to the written and illustrated contents shown above without departing from the gist of the technology of the present disclosure. Needless to say. In addition, in order to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the descriptions and illustrations shown above do not include parts that require particular explanation in order to enable implementation of the technology of the present disclosure. Explanations regarding technical common sense that should not be used are omitted.

The 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 mentioned herein are incorporated by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference. Incorporated herein by reference.

Claims (9)

A storage tank capable of accommodating a sample container and storing a fluid heat medium around the sample container for changing the temperature of a sample solution in the sample container , a storage tank provided with a supply port for supplying the heat medium and a discharge port for discharging the heat medium ;
a heat medium supply unit that supplies the heat medium;
A heat medium exchange mechanism for exchanging a heat medium in the storage tank, the first heat medium for heating the sample solution in the sample container to a first temperature, and a second temperature lower than the first temperature. a heat medium exchange mechanism for exchanging the heat medium with a second heat medium for cooling the sample solution;
A supply path that is a part of piping and supplies the heat medium supplied from the heat medium supply section to the supply port, the length of the first direction in the cross-sectional shape being the same as the first direction. a supply path shorter than the length in the orthogonal second direction;
a discharge path that is part of the piping and returns the heat medium discharged from the discharge port to the heat medium supply section;
The heating medium is disposed in close contact with the supply path along the second direction, and is converted into the first heating medium by heating the heating medium to the first temperature or higher before being supplied to the supply port. a first temperature adjustment section,
The heating medium is disposed in close contact with the supply path along the second direction, and is converted into the second heating medium by cooling the heating medium to a temperature equal to or lower than the second temperature before being supplied to the supply port. a second temperature adjustment section ,
The heat medium exchange mechanism circulates the first heat medium or the second heat medium in the storage tank through piping connected to the supply port and the discharge port.
Processing equipment. The processing apparatus according to claim 1 , wherein the heat medium is a liquid. A control unit that controls the heat medium exchange mechanism to supply the second heat medium to the storage tank after a preset time has elapsed since the first heat medium was supplied to the storage tank. The processing device according to claim 1 or 2 . comprising a heater that heats the heat medium to use it as the first heat medium;
The processing apparatus according to any one of claims 1 to 3 , wherein the temperature of the heater is 30°C or more and 80°C or less. The processing apparatus according to claim 4 , wherein the temperature of the heater is 60°C or more and 80°C or less. comprising a cooling element that cools the heat medium to use it as the second heat medium;
The processing apparatus according to any one of claims 1 to 5 , wherein the temperature of the cooling element is 0°C or more and 10°C or less. The processing device according to any one of claims 1 to 6 , wherein the storage tank is configured to accommodate a plurality of the sample containers. The sample solution is a measurement target for measurement using a reagent containing a horseshoe crab blood cell extract,
The processing apparatus according to any one of claims 1 to 7 , wherein the process of changing the temperature of the sample solution by the heat medium exchange mechanism is preprocessing performed before performing the measurement. A processing device according to any one of claims 1 to 8 ,
A measurement system comprising: a measurement device that performs measurement on the sample solution.