JP7297946B2 - Processing equipment and measurement systems - Google Patents

Description

The present disclosure relates to processing devices and measurement systems.

In order to analyze a specimen such as a biological sample, various substances contained in the specimen are measured. As such a measurement, 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 induces biological reactions such as fever when even a very small amount enters the blood. Specimens include biological samples such as blood, as well as pharmaceuticals (for example, injections, etc.) that are directly introduced into a living body. When performing measurement using such a lysate reagent, pretreatment such as heating the sample solution and then cooling the sample solution may be performed prior to measurement. It is

Japanese Patent Application Laid-Open No. 8-29432 discloses a processing apparatus comprising a heating unit for heating a sample container, a cooling unit for cooling the container, and a transport mechanism for transporting the container heated by the heating unit to the cooling unit. It is The transport mechanism is a handling robot, which grips the containers one by one and transfers the containers from the heating unit to the cooling unit (see FIG. 6 of Japanese Patent Application Laid-Open No. 8-29432).

Further, Japanese National Publication of International Patent Application No. 2007-510911 discloses an apparatus for online testing for the presence of endotoxin in a fluid sample. The apparatus includes a heating system for providing heat to the assembly, a cooling system for maintaining a cool ambient temperature of the container within the assembly, and a transport mechanism for transporting the container heated by the heating system to the cooling system. there is The transport mechanism described in Japanese Patent Application Publication No. 2007-510911 has a lifting fork that grips the containers one by one, and the lifting fork is used to transfer the container from the heating system to the cooling system (Japanese Patent Application Publication No. 2007-510911 20 to 23 of the publication).

However, in the processing apparatus disclosed in Japanese Patent Application Laid-Open No. 8-29432, the handling robot grips the containers one by one and transfers them from the heating unit to the cooling unit, so it is difficult to transfer the containers easily and quickly. Similarly, in the processing apparatus described in Japanese Patent Application Publication No. 2007-510911, the containers are held one by one by a lifting fork and transferred from the heating system to the cooling system, so it is difficult to transfer the containers easily and quickly.

This is because the handling robot described in Japanese Patent Application Laid-Open No. 8-29432 is capable of rapid transfer if it is highly functional, but on the other hand, the device configuration tends to be complicated, making it difficult to simplify the configuration. There's a problem.

In addition, the lifting fork described in Japanese Patent Application Publication No. 2007-510911 requires a combination of a lifting operation for vertically moving the container and a moving operation for horizontally moving the container when transferring the container. When a general motor is used as a driving source for a lifting fork, it is necessary to convert the rotary motion of the rotating shaft of the motor into a vertical up-and-down motion and a horizontal movement motion orthogonal to the vertical direction. In this case, it is necessary to use multiple motors for each vertical and horizontal direction, or the link mechanism for converting the rotary motion of the motor into vertical and horizontal linear motion becomes complicated. The device configuration tends to be complicated. In addition, when combining a plurality of operations in orthogonal directions, there is a tendency for the transfer speed to decrease due to the need to change directions in the orthogonal directions.

In order to obtain high measurement accuracy, it may be necessary to quickly cool the specimen solution after heating it. In addition, there is also the problem that a complicated device configuration increases the cost and is difficult to accept depending on the market. Therefore, a simple and rapid processing apparatus is desired.

In addition, since the transport mechanisms described in JP-A-8-29432 and JP-A-2007-510911 both transport containers one by one, there is also the problem that it is difficult to improve the processing throughput.

The present disclosure has been made in view of the circumstances described above, and aims to provide a processing apparatus and a measurement system capable of easily and quickly transferring a plurality of sample containers from a heating block to a cooling block.

A processing apparatus according to a first aspect of the present disclosure is a processing apparatus that performs a process of changing the temperature of a sample solution in which a sample and a processing liquid are mixed, wherein a sample container containing the sample solution is inserted from above, and A heating block that has a plurality of first housing units that surround and house a specimen container and that heats the specimen solution in the specimen container to a first temperature; A cooling block that has a plurality of second storage units that surround the circumference and cools the sample solution in the sample container to a second temperature that is lower than the first temperature, and a holding unit that holds the plurality of sample containers. and a track portion for guiding the holding portion in an upwardly convex inverted U-shaped track when transferring a plurality of specimen containers from the heating block to the cooling block, and the holding portion is arranged in an inverted U-shaped a transfer mechanism that draws out the plurality of sample containers upward from the first container by moving along the track, moves the plurality of sample containers downward from above, and inserts the plurality of sample containers into the second container. .

In the processing apparatus of the aspect described above, the cooling block may include a discharge section for discharging condensed water from the specimen container below the second storage section.

Further, in the processing apparatus of the above aspect, the control unit causes the transfer mechanism to transfer the sample container to the second container at a preset time after the sample container is accommodated in the first container. may be provided.

Moreover, the processing apparatus of the above aspect preferably includes a heater for heating the heating block, and the temperature of the heater is preferably 30° C. or higher and 80° C. or lower. More preferably, the temperature of the heater is 60° C. or higher and 80° C. or lower.

Moreover, it is preferable that the processing apparatus of the above aspect includes a cooling section for cooling the cooling block, and the temperature of the cooling section is set to 0° C. or higher and 10° C. or lower.

Further, in the processing apparatus of the above aspect, the sample solution is the object to be measured using the reagent containing the horseshoe crab blood cell extract, and the process of changing the temperature of the sample solution by the heating block and the cooling block performs the measurement. It may be a pretreatment that is performed before performing the treatment.

A measurement system according to a second 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, it is possible to provide a processing apparatus and a measurement system that can easily and quickly transfer a plurality of sample containers from a heating block to a cooling block.

It is a figure which shows the outline of a measurement system. 4 is a graph showing changes in temperature of a sample solution during pretreatment. BRIEF DESCRIPTION OF THE DRAWINGS It is a schematic perspective view which shows the structure of the processing apparatus which concerns on 1st Embodiment. It is a top view of a temperature control part. FIG. 4 is a plan view of a cooling block; 5B is a cross-sectional view of the cooling block along line 5B-5B in FIG. 5A; FIG. 4 is an exploded perspective view of the transfer mechanism; FIG. FIG. 10 is a front view showing the state of movement of the holding part by the transfer mechanism, and shows the state during heating when the holding part is moved to the heating side. FIG. 10 is a front view showing a state in which the holding section is moved by the transfer mechanism, and shows a state in the middle of moving the holding section. FIG. 10 is a front view showing a state of movement of the holding part by the transfer mechanism, showing a state during cooling when the holding part is moved to the cooling side; It is a block diagram which shows the hardware constitutions of a processing apparatus. 1 is a schematic diagram showing the configuration of a measuring device; FIG. 4 is a flowchart for explaining the flow of preprocessing in the processing device; It is a figure which shows the state at the time of heating in a processing apparatus. It is a figure which shows the state at the time of transfer in a processing apparatus. It is a figure which shows the state at the time of cooling in a processing apparatus.

[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 the 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. As shown in FIG. The processing device 10 performs pretreatment before endotoxin measurement on a sample solution C generated by adding a buffer solution B to a sample A such as a biological sample and diluting the sample. The measurement device 60 performs endotoxin measurement using the sample solution C after pretreatment as a measurement target.

As described above, endotoxin is a typical pyrogen that causes a biological reaction such as fever when it enters the blood even in a very small amount. pharmaceuticals (for example, injections, etc.); In the endotoxin measurement, the amount of endotoxin in sample solution C is measured, and endotoxin in sample A is quantified. Endotoxin measurement is a measurement using reagents such as Lysate Reagent D containing horseshoe crab blood cell extract. Endotoxin measurement is a measurement that utilizes the aggregation and coagulation of horseshoe crab blood cell extract caused by endotoxin. In endotoxin measurement, first, a lysate reagent D containing a horseshoe crab blood cell extract is added to a 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 changes in the properties of the sample solution E.

A lysate reagent prepared from a blood cell extract of the Limulus polyphemus, which is the raw material of the lysate reagent D, is called a LAL (Limulus Amebocyte Lysate) reagent.

The measurement device 60 in the measurement system 1 of the first embodiment uses the LAL reagent as the lysate reagent D, and uses the change in turbidity of the sample solution E during the gelation process of the lysate reagent D by reaction with endotoxin as an index. Endotoxin determination is performed by nephelometric method. When performing endotoxin measurement by the nephelometric method, it is necessary to pretreat the sample solution C by heating and cooling prior to the measurement. As shown in FIG. 1, a sample solution C is pretreated, and a sample solution E containing a pretreated sample solution C and a lysate reagent D is subjected to endotoxin measurement.

Specifically, as shown in the graph of FIG. 2, the pretreatment for endotoxin measurement by the turbidimetric method is first performed by adding buffer B to sample A and diluting sample solution C to about By heating at a temperature of 70° C. for about 10 minutes, heat treatment is performed to inactivate interfering factors in endotoxin measurement. After that, the sample solution C at approximately 70°C is cooled to a temperature of approximately 5°C, thereby performing a cooling process for stopping the inactivation process. 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°C to a temperature of about 5°C, the inactivation time for the sample solution C will vary 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 approximately 70°C to a temperature of approximately 5°C in a short period of time.

The processing device 10 in the measurement system 1 of the first embodiment is a device that performs the pretreatment described above on the sample solution C obtained by adding the buffer solution B to the sample A and diluting it.

<Processing device>
The front side, the upper side, and the rear side in the width direction, which are used in the following description, respectively correspond to the directions of arrows indicated by "FR", "UP", and "W" in each drawing. These directions are set for convenience of explanation, and do not necessarily match the front, back, left, and right of the actual product.

FIG. 3 is a schematic perspective view showing the configuration of the processing apparatus 10. As shown in FIG. As shown in FIG. 3 , the processing apparatus 10 includes a temperature adjustment section 30 , a transfer mechanism 12 and a control section 11 . The transfer mechanism 12 includes a holding section 20 that holds the sample container 5 . The temperature adjustment section 30 includes a heating block 31 and a cooling block 32 . The transfer mechanism 12 transfers the specimen container 5 from the heating block 31 to the cooling block 32 by moving the holder 20 holding the specimen container 5 . The specimen container 5 loaded into the processing apparatus 10 has a cylindrical appearance and includes a main body 5b and a lid 5a.

The controller 11 includes a transfer mechanism controller 11a, a heater controller 11b, and a cooling controller 11c. The transfer mechanism control section 11 a controls the transfer mechanism 12 . The heater control unit 11 b controls the heater 41 that heats the heating block 31 . The cooling control unit 11 c controls the cooling device 43 that cools the cooling block 32 .

The holding part 20 is, for example, a rectangular plate-like body, and is arranged so that the thickness direction of the holding part 20 is the vertical direction. Here, the vertical direction is the vertical direction. The longitudinal direction of the holding part 20 extends along the width direction of the processing apparatus 10 (the arrow W direction in the first embodiment). A plurality of container holding holes 20b for holding the specimen container 5 are formed in the holding part 20 at intervals in the longitudinal direction. The container holding hole 20b penetrates from the upper surface 20a of the holding portion 20 toward the lower surface (not shown). The sample container 5 is a cylindrical body with a bottom. The specimen container 5 is inserted into the container holding hole 20b in a posture in which the longitudinal direction in which the cylinder axis extends coincides with the vertical direction. The container holding hole 20b is configured to hold an intermediate portion of the sample container 5 in the longitudinal direction. An opening edge of the container holding hole 20b on the side of the upper surface 20a is formed with an inclined surface whose inner diameter gradually increases upward. The inclined surface functions as a guide surface that guides the sample container 5 to the center of the container holding hole 20b.

The processing device 10 can perform preprocessing on a plurality of sample containers 5 at the same time. Therefore, in the holding portion 20 of the first embodiment, a plurality of container holding holes 20b, for example ten container holding holes 20b, are arranged in a line along the longitudinal direction. The inner diameter of the container holding hole 20b is formed slightly larger than the outer diameter of the specimen container 5, but they are substantially the same diameter. An elastic ring (not shown) made of, for example, rubber is provided on the inner peripheral surface of the container holding hole 20b. The inner diameter of the elastic ring is formed smaller than the outer shape of the specimen container 5 . The sample container 5 is inserted through the container holding hole 20b while being pressed against the elastic ring. The holding part 20 holds the sample container 5 by frictional force generated by pressure contact with the elastic ring. The specimen container 5 is held in a state in which it is inserted into the container holding hole 20b up to the intermediate portion in the longitudinal direction. Since the container holding hole 20b and the sample container 5 have substantially the same diameter, the sample container 5 is held in the container holding hole 20b without tilting in the longitudinal direction with respect to the vertical direction.

Since the holding section 20 transfers the specimen container 5, it is preferable that the holding section 20 is lightweight. This is because the lighter the weight, the smaller the driving force of the transfer mechanism 12, which contributes to the simplification of the configuration. Therefore, it is preferable that the material forming the holding portion 20 is a material having a small specific gravity. Moreover, it is preferable that the material forming the holding portion 20 has a small heat capacity and a low thermal conductivity. This is because when the holding portion 20 has a small heat capacity and a low thermal conductivity, it is difficult for the heating block 31 and the cooling block 32 to absorb heat, and temperature changes in the heating block 31 and the cooling block 32 themselves can be reduced. A resin material such as a copolymer resin of acrylonitrile, butadiene, and styrene (that is, ABS resin) is used as a material forming the holding portion 20 . Details of members other than the holding portion 20 of the transfer mechanism 12 will be described later.

FIG. 4 is a plan view of the temperature adjustment section 30. FIG. As shown in FIGS. 3 and 4, the temperature adjustment section 30 includes a heating block 31, a cooling block 32, and a heat insulating material 33. As shown in FIGS. The heating block 31, the heat insulating material 33, and the cooling block 32 are arranged in this order from the front side (see arrow FR) of the processing apparatus 10 toward the rear side.

The heating block 31 includes a block body 40 and a heater 41 that heats the block body 40 to a first temperature.

The block body 40 is, for example, a rectangular parallelepiped, and is arranged so that its longitudinal direction is the width direction (see arrow W) of the processing device 10 . A plurality of container insertion holes 40b for inserting sample containers 5 are formed in the upper surface 40a of the block body 40. As shown in FIG. A container insertion hole 40b formed in the block main body 40 is an example of a first container into which a sample container 5 containing a sample solution is inserted from above and accommodates the sample container 5 while surrounding it. In the block body 40, the bottom of the container insertion hole 40b is closed. When the sample container 5 is inserted into the container insertion hole 40b from above, the block body 40 accommodates the sample container 5 while enclosing the middle portion and the lower portion of the sample container 5 . An opening edge of the container insertion hole 40b on the side of the upper surface 40a is formed with an inclined surface whose inner diameter gradually increases upward. The inclined surface functions as a guide surface that guides the sample container 5 to the center of the container insertion hole 40b in the same manner as the inclined surface formed on the opening edge of the container holding hole 20b on the side of the upper surface 20a.

As with the container holding holes 20b of the holding portion 20, in the block body 40 of the first embodiment, a plurality of container insertion holes 40b, for example ten container insertion holes 40b, are arranged in a line along the longitudinal direction. arranged side by side. As a result, the heating block 31 can heat a plurality of sample containers 5 at the same time. The inner diameter of the container insertion hole 40 b is formed slightly larger than the outer diameter of the specimen container 5 . Therefore, when the sample container 5 is inserted into the container insertion hole 40b, the sample container 5 is held in the container insertion hole 40b without tilting.

The material forming the block body 40 is preferably a material with excellent thermal conductivity so that the heat of the heater 41 can be efficiently transferred to the specimen container 5 . Furthermore, since the block main body 40 forms a plurality of container insertion holes 40b, it is preferable that the block body 40 be made of a material with high workability. Aluminum, for example, can be used as a material that satisfies these conditions. In the first embodiment, the block body 40 is made of aluminum.

The heater 41 is mounted so that its heat generating surface is in direct contact with the side surface 40 d of the block body 40 opposite to the cooling block 32 . As a pretreatment for the sample solution C when performing endotoxin measurement by the nephelometric method, heating is preferably performed at 30° C. or higher and 80° C. or lower, more preferably 60° C. or higher and 80° C. or lower. Therefore, the temperature of the heater 41 is preferably set at 30° C. or higher and 80° C. or lower, and more preferably set at 60° C. or higher and 80° C. or lower. In the first embodiment, the temperature of the heater 41 is set to 70° C. (an example of the first temperature) under the control of the heater control section 11 b of the control section 11 . The heater 41 heats the block body 40 to about 70°C, and the sample solution C in the sample container 5 inserted into the container insertion hole 40b is heated to about 70°C.

The cooling block 32 includes a block body 42 and a cooling device 43 that cools the block body 42 to the second temperature.

FIG. 5A is a plan view showing a portion of the block body 42 enlarged from FIG. 4, and FIG. 5B is a cross-sectional view taken along line 5B-5B in FIG. 5A. As shown in FIGS. 3 to 5B, the block body 42 is, for example, a rectangular parallelepiped, and is arranged so that its longitudinal direction is the width direction (see arrow W) of the processing apparatus 10 . A plurality of container insertion holes 42b for inserting sample containers 5 are formed in the upper surface 42a of the block body 42 . The container insertion hole 42b formed in the block main body 42 is an example of a second accommodation portion into which the specimen container 5 is inserted from above and accommodates the specimen container 5 in a surrounding state. When the sample container 5 is inserted into the container insertion hole 42b from above, the block body 42 accommodates the sample container 5 while enclosing the intermediate portion and the lower portion of the sample container 5 . An opening edge of the container insertion hole 42b on the side of the upper surface 42a is formed with an inclined surface whose inner diameter gradually increases upward. The inclined surface functions as a guide surface that guides the sample container 5 to the center of the container insertion hole 42b in the same manner as the inclined surface formed on the opening edge of the container holding hole 20b on the side of the upper surface 20a.

As with the container holding holes 20b of the holding portion 20, in the block body 42 of the first embodiment, a plurality of container insertion holes 42b, for example ten container insertion holes 42b, are arranged in a line. As a result, the cooling block 32 can simultaneously perform cooling processing on a plurality of sample containers 5 . The inner diameter of the container insertion hole 42b is formed slightly larger than the outer diameter of the specimen container 5 . Therefore, when the sample container 5 is inserted into the container insertion hole 42b, the sample container 5 is held in the container insertion hole 42b without tilting.

Below the container insertion hole 42b in the block body 42, a discharge hole 44 is formed that opens to the lower surface 42e of the block body 42. As shown in FIG. That is, the discharge hole 44 is vertically formed from the lower portion of the container insertion hole 42b toward the lower surface 42e of the block body 42. As shown in FIG. The discharge hole 44 is an example of a discharge portion. By providing the discharge hole 44 below the container insertion hole 42b, the condensed water of the sample container 5 is discharged from the discharge hole 44 when the sample container 5 is inserted into the container insertion hole 42b.

The material forming the block body 42 is preferably a material having excellent thermal conductivity in order to efficiently cool the specimen container 5 by the cooling device 43 . Furthermore, since the block body 42 is formed with a plurality of container insertion holes 42b, it is preferable that the block body 42 be made of a material with high workability. In the first embodiment, the block body 42 is made of the same material as the block body 40, namely aluminum.

The cooling device 43 includes a body portion 43a and a cooling element 43b. Cooling device 43 is an example of a cooling unit. The cooling element 43b is a portion that contacts the block body 42 to be cooled, and has a plate shape. The cooling element 43b is, for example, a Peltier element. The cooling element 43b is mounted in direct contact with the side surface 42c of the block body 42 opposite to the heating block 31. As shown in FIG. The body portion 43a is a driving portion that drives the cooling element 43b. The cooling device 43 cools the sample solution C contained in the sample container 5 in the block body 42 to a preset second temperature by cooling the block body 42 through the cooling element 43b. As a pretreatment for the sample solution C when performing endotoxin measurement by the nephelometric method, it is preferable to cool the sample solution C at 0°C or higher and 10°C or lower. Therefore, the temperature of the cooling element 43b can be set between 0°C and 10°C. In the first embodiment, the temperature of the cooling element 43b is set to a temperature that can cool the block body 42 to 5° C. (an example of the second temperature) under the control of the cooling control section 11c of the control section 11 . The cooling element 43b cools the block body 42 to approximately 5°C, thereby cooling the sample solution C in the sample container 5 inserted into the container insertion hole 42b to approximately 5°C.

A heat insulator 33 is arranged between the heating block 31 and the cooling block 32 . One side of the heat insulating material 33 is in contact with a side surface 40c of the block body 40 opposite to the heater 41, and the other side of the heat insulating material 33 is in contact with a side surface 40d of the block body 42 opposite to the cooling element 43b. ing. The heat insulating material 33 is a material that suppresses heat transfer from the heating block 31 to the cooling block 32 . Therefore, the heat insulating material 33 is preferably made of a material having a lower thermal conductivity than the block body 40 of the heating block 31 and the block body 42 of the cooling block 32 .

6 is an exploded perspective view of the transfer mechanism 12. FIG. As shown in FIG. 6, the transfer mechanism 12 includes a holding portion 20, a support rod 50, a guide plate 51, an arm 52, and a motor 53.

The support rod 50 has a cylindrical shape and is provided at the longitudinal end of the holding portion 20 . The support rod 50 is arranged such that its axial direction is the longitudinal direction of the holding portion 20 .

The guide plate 51 includes guide rails 57 through which the support rods 50 are inserted. The guide rail 57 is an example of a track portion. The guide rail 57 is an inverted U-shaped through-hole that protrudes upward. That is, the guide rail 57 has an inverted U-shaped track that connects three points: one end portion 57a on the lower side, a top portion 57c that is the intermediate portion on the upper side, and the other end portion 57b on the lower side. More specifically, the inverted U-shaped trajectory includes a linear trajectory extending linearly in the vertical direction from one end 57a and the other end 57b on the lower side, and an arch-shaped trajectory connecting the upper ends of each linear trajectory. and The guide rail 57 having an inverted U-shaped track guides the vertical movement of the support rod 50 with a straight track, and guides the lateral movement of the support rod 50 with an arch-shaped track.

One end 57a of the guide rail 57 faces the heating block 31, and the other end 57b of the guide rail 57 faces the cooling block 32 (see FIG. 3). The top portion 57c of the guide rail 57 is located above the heat insulating material 33 between the heating block 31 and the cooling block 32 in the front-rear direction (see the FR direction) of the processing apparatus 10 .

With the support rod 50 inserted through the guide rail 57, the support rod 50 moves from one end 57a of the guide rail 57 to the other end 57b via the top 57c, thereby forming an upwardly convex inverted U-shaped trajectory. , the holding part 20 is guided. In a state where the holding part 20 is guided by the top part 57c of the guide rail 57, the specimen container 5 held by the holding part 20 is arranged above the heat insulating material 33 (see FIG. 3). That is, in a state where the holding part 20 is guided by the top part 57c of the guide rail 57, the sample container 5 held by the holding part 20 is pulled from the container insertion hole 40b of the heating block 31 and the container insertion hole 42b of the cooling block 32. It will be removed.

When the support rod 50 moves along the guide rail 57, the holding part 20 maintains a posture in which the upper surface 20a faces upward. For example, in the holding portion 20, by making the lower side relatively heavier than the upper surface 20a, the posture in which the upper surface 20a of the holding portion 20 faces upward is maintained. Note that the holding portion 20 may be rotatably attached to the support rod 50 . With this configuration, even if the support rod 50 rotates around the axis in the guide rail 57 while the guide rail 57 is moving, the rotation of the holding portion 20 with respect to the support rod 50 causes the upper surface of the holding portion 20 to move. It is possible to maintain a posture in which 20a faces upward.

The arm 52 is made of an elongated plate material, and has an elongated hole 58 through which the support rod 50 is inserted at one end 52a in the longitudinal direction. The long hole 58 is an oval through hole arranged along the longitudinal direction of the arm 52 . The elongated hole 58 has an inner diameter that is slightly larger than the outer diameter of the support rod 50 in the direction orthogonal to the longitudinal direction. This allows the support rod 50 to move in the long hole 58 along the longitudinal direction.

An opening 54 is formed at the other end 52b of the arm 52 in the longitudinal direction. The opening 54 has a substantially circular shape. A shaft 55 is inserted into the opening 54 of the arm 52, and the arm 52 and the shaft 55 are joined by adhesion or welding. The shaft 55 is connected to the motor 53 and rotates about its axis. The arm 52 swings between the heating block 31 side and the cooling block 32 side due to the rotation of the shaft 55 (see arrows F1 and F2 in FIG. 2).

Although not shown, a support frame is provided at the end of the support rod 50 opposite to the holding section 20 . The support frame is attached to a moving mechanism (not shown) that is movable in, for example, the longitudinal direction (see the FR direction) and the vertical direction, and the support rod 50 is moved along the inverted U-shaped track of the guide rail 57. Support movable.

In the transfer mechanism 12 , the arm 52 swings from the heating block 31 side to the cooling block 32 side while the support rod 50 is inserted through the elongated hole 58 of the arm 52 . As a result, as shown in FIGS. 7A, 7B, and 7C, the support rod 50 moves from the position on the side of the one end portion 57a of the guide rail 57 (see FIG. 7A) to the position on the top portion 57c of the guide rail 57 (see FIG. 7B). , to the position on the other end 57b side of the guide rail 57 (see FIG. 7C). At this time, the support rod 50 relatively moves within the long hole 58 of the arm 52 according to the distance of the guide rail 57 from the center of the shaft 55 . As the support rod 50 moves while being guided by the guide rail 57 , the holding portion 20 moves along the inverted U-shaped track of the guide rail 57 . Thereby, each of the plurality of sample containers 5 held by the holding section 20 is pulled upward from the container insertion hole 40 b of the heating block 31 . Then, the plurality of specimen containers 5 pulled out from the heating block 31 are guided laterally from above the heating block 31 to above the cooling block 32 by the inverted U-shaped arch-shaped trajectory. After that, the plurality of specimen containers 5 are guided downward from above the cooling block 32 and inserted into the container insertion holes 42 b of the cooling block 32 .

As shown in FIG. 8, the control unit 11 includes a CPU (Central Processing Unit) 14a, a memory 14b, and a storage 14c in which a control program 15 is stored. The memory 14b is a work memory used when the CPU 14a executes the program 15, and for example, a volatile memory is used. The storage 14c is a non-volatile memory for storing various data, and flash memory or the like is used. Although illustration is omitted, the control section 11 may include a timer for measuring the operation timing of the transfer mechanism 12 . For example, the timer measures the heating time and cooling time of the specimen container 5 held by the holding section 20 . By executing the program 15, the CPU 14a functions as a heater control section 11b that controls the heater 41, a cooling control section 11c that controls the cooling element 43b, and a transfer mechanism control section 11a that controls the transfer mechanism 12. FIG.

<Measuring device>
FIG. 9 is a schematic diagram showing the configuration of the measuring device 60. As shown in FIG. As shown in FIG. 9, the measurement device 60 includes an LED 61 that irradiates the sample container 5 with measurement light, a photodiode 62 that faces the LED 61 with the sample container 5 interposed therebetween, the LED 61 and the photodiode. 62 and a measurement control unit 63 that measures the amount of endotoxin in the sample solution E based on the detection result of the photodiode 62 . The measurement control section 63 measures the amount of endotoxin in the sample solution E based on the detection result of the photodiode 62 . Also, the measurement control unit 63 controls the LED 61 and the photodiode 62 . A sample solution E in which a lysate reagent D is mixed with a sample solution C after pretreatment is contained in the sample container 5 .

The measurement control section 63 includes a CPU (Central Processing Unit) 63a, a memory 63b, and a storage 63c in which a control program is stored. The memory 63b is a work memory used when the CPU 63a executes the measurement control program, and for example, a volatile memory is used. The storage 63c is a non-volatile memory for storing various data, and 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 photodiode 62 by executing a measurement control program. The measurement control unit 63 also functions as a measurement unit that measures the amount of endotoxin in the sample solution E based on the detection result of the photodiode 62 by executing the measurement control program.

As a technique for measuring endotoxin in the measuring device 60, the turbidimetric method is used as described above. The turbidimetric method is a technique that uses as an index the change in turbidity during the gelation process of the 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 after adding the lysate reagent D to the sample solution C after pretreatment. When the turbidity of the sample solution E changes, the amount of measurement light that passes through the sample solution E also changes. can be measured. The measurement control unit 63 calculates the amount of endotoxin in the sample solution E based on the turbidity state and transition of the sample solution E. FIG.

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

First, a sample solution C is produced by adding a buffer solution B to a sample A and diluting it. The control section 11 controls the transfer mechanism 12 by the transfer mechanism control section 11 a to move the holding section 20 to the top portion 57 c side of the guide rail 57 . The user sets the sample container 5 in the holding unit 20 by inserting the sample container 5 containing the generated sample solution C into the container holding hole 20b of the holding unit 20 (see step S100).

The control unit 11 determines whether or not there is a preprocessing start instruction (see step S101). In step S100, when it is determined that there is no preprocessing start instruction (that is, the determination result is No), the control unit 11 waits until there is a preprocessing start instruction.

If it is determined in step S100 that there is a pretreatment start instruction (that is, the determination result is Yes), the control unit 11 transfers the sample container 5 held by the holding unit 20 to the heating block 31 side (see step S102). ). Specifically, the control section 11 controls the transfer mechanism 12 by the transfer mechanism control section 11a to move the holding section 20 to the heating block 31 side. Specifically, as shown in FIG. 7A, when the holding section 20 moves toward the one end portion 57a of the guide rail 57, the specimen container 5 held by the holding section 20 moves from the block main body 40 as shown in FIG. 11A. It is inserted into the container insertion hole 40b.

When transfer of the specimen container 5 to the heating block 31 is completed, the controller 11 starts heating the specimen container 5 (see step S103). Thereby, the heating of the sample solution C in the sample container 5 is started. The control unit 11 controls the heater 41 by the heater control unit 11 b so that the sample solution C in the sample container 5 is heated through the heating of the block body 40 . Note that the heat insulating material 33 between the heating block 31 and the cooling block 32 is omitted in FIGS. 11A, 11B and 11C. 11A, 11B, and 11C, one specimen container 5 is held in the holding section 20, but the holding section 20 may hold 2 or more and 10 or less specimen containers 5. FIG. If a plurality of sample containers 5 are held in the holding section 20, pretreatment can be performed on the plurality of sample containers 5 at the same time.

The control unit 11 determines whether or not the heating time Th (10 minutes in the first embodiment) has elapsed (see step S104). If it is determined in step S104 that the heating time Th has not elapsed (that is, the determination result is No), the controller 11 waits until the heating time Th elapses.

When it is determined in step S104 that the heating time Th has elapsed (that is, the determination result is Yes), the control unit 11 transfers the sample container 5 held by the holding unit 20 from the heating block 31 to the cooling block 32 ( See step S105). That is, the control section 11 controls the transfer mechanism 12 by the transfer mechanism control section 11a to move the holding section 20 from the heating block 31 side to the cooling block 32 side. Specifically, as shown in FIG. 7B, in the process in which the holding section 20 moves to the top portion 57c of the guide rail 57, the sample container 5 held by the holding section 20 is moved from the block main body 40 as shown in FIG. 11B. It is drawn upward from the container insertion hole 40b. Thereby, the heating of the sample solution C in the sample container 5 is completed.

The control unit 11 starts cooling the sample container 5 (see step S106). Specifically, as shown in FIG. 7C, when the holding section 20 moves toward the one end portion 57a of the guide rail 57, the sample container 5 held by the holding section 20 moves downward from above as shown in FIG. 11C. The sample container 5 is moved and inserted into the container insertion hole 42 b of the block body 42 in the cooling block 32 . Thereby, the cooling of the sample solution C in the sample container 5 is started. The control unit 11 controls the cooling element 43b by the cooling control unit 11c to cool the sample solution C in the sample container 5 through the cooling of the block body 42 .

Next, the control unit 11 determines whether or not the cooling time Tc (three minutes in the first embodiment) has elapsed from the start of cooling (see step S107). If it is determined in step S107 that the cooling time Tc has not elapsed (that is, the determination result is No), the controller 11 waits until the cooling time Tc has elapsed.

When it is determined in step S107 that the cooling time Tc has elapsed (that is, the determination result is Yes), the control unit 11 terminates the process.

[Effect]
As described above, the processing apparatus 10 of the first embodiment includes the holding unit 20 that holds the plurality of sample containers 5 and the upward movement of the plurality of sample containers 5 from the heating block 31 to the cooling block 32. The transfer mechanism 12 includes a guide rail 57 that guides the holding portion 20 on a convex inverted U-shaped track. By moving the holding part 20 along the guide rails 57, the plurality of sample containers 5 are pulled upward from the container insertion holes 40b, respectively, and then the plurality of sample containers 5 are moved downward from the top to the container insertion holes. 42b. Since the trajectory of the holding part 20 is an inverted U-shaped trajectory that is convex upward, the link mechanism can be simplified compared to the conventional case where the rotary motion of the motor is converted into motion in two orthogonal directions. Cheap.

Moreover, since the guide rail 57 is an inverted U-shaped track, it is not necessary to change the moving direction to the orthogonal direction. Therefore, in the processing apparatus 10, there is less concern about a decrease in moving speed, and the holding section 20 can be moved smoothly as compared with the conventional apparatus.

The reason why the holding part 20 can be moved smoothly is as follows. That is, the transfer mechanism 12 is configured to transfer the specimen container 5 between two points from the heating block 31 toward the cooling block 32 . More specifically, the transfer mechanism 12 moves the specimen container 5 vertically linearly up and down with respect to the heating block 31 and the cooling block 32 , and moves the specimen between the heating block 31 and the cooling block 32 . and a movement operation for moving the container 5 in the lateral direction. In an inverted U-shaped trajectory, the up-and-down motion corresponds to a straight trajectory in the vertical direction, and the lateral movement motion corresponds to a curved, arched trajectory at the top of the inverted U-shape. Further, by forming an inverted U-shape, it is possible to continuously connect a straight track and an arch-shaped curved track. For this reason, compared with the conventional art in which each of the vertical movement and the horizontal movement is carried out on a straight track, and each track has an intersection at right angles, the inverted U-shaped track allows the holder 20 to move smoothly. Cheap.

In addition, the support rod 50 supporting the holding part 20 is moved in an inverted U shape along the guide rail 57 by rotating the arm 52 having the long hole 58 that engages with the support rod 50 . By forming an inverted U-shaped curvilinear trajectory in this way, one motor 53 is enough for the actuator that drives the holding portion 20, so the configuration of the transfer mechanism 12 can be simplified more easily.

In addition, since the holding unit 20 can hold a plurality of sample containers 5, the processing throughput is improved as compared with the conventional method in which the containers are transported one by one.

In addition, in the processing apparatus 10 of the first embodiment, the cooling block 32 has a discharge hole 44 for discharging condensed water from the sample container 5 below the container insertion hole 42b in the block body 42 . Therefore, in the processing apparatus 10, even if condensation occurs in the sample container 5 in the container insertion hole 42b of the cooling block 32, the condensed water can be discharged from the discharge hole 44 below the container insertion hole 42b.

Further, the processing apparatus 10 of the first embodiment transfers the sample container 5 to the container insertion hole 42b of the block body 42 after the sample container 5 is accommodated in the container insertion hole 40b of the block body 40 with respect to the transfer mechanism 12. A transfer mechanism control unit 11a is provided for causing the heating time Th set in advance to be performed. Therefore, in the processing apparatus 10, the heating of the specimen solution E in the specimen container 5 by the heating block 31 can be controlled to the preset heating time Th by the transfer mechanism control section 11a.

The processing apparatus 10 of the first embodiment also includes a heater 41 for heating the heating block 31, and the temperature of the heater 41 is set to 60° C. or higher and 80° C. or lower. Therefore, the processing apparatus 10 can perform pretreatment suitable for endotoxin measurement by the nephelometric method.

The processing apparatus 10 of the first embodiment also includes a cooling element 43b for cooling the cooling block 32, and the temperature of the cooling element 43b is set to 0°C or higher and 10°C or lower. Therefore, the processing apparatus 10 can perform pretreatment suitable for endotoxin measurement by the nephelometric method.

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

In addition, 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 Tachypleus tridentatus, which is a species different from the American horseshoe crab, may be used.

In addition, the endotoxin test method is not limited to the turbidimetric method described in the above embodiment, but may be a gelation method using the gel formation of a lysate reagent by the action of endotoxin as an index, or a color development due to hydrolysis of a synthetic substrate as an index. A colorimetric method may be used to

Further, the measurement using the horseshoe crab blood cell extract is not limited to endotoxin measurement, and may be β-glucan measurement.

Moreover, the measurement performed by the measuring device is not limited to the measurement using the horseshoe crab blood cell extract, and other measurements may be performed.

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

In the above embodiment, the hardware structure of the processing unit (Processing Unit) that executes various processes such as the transfer mechanism control unit 11a, the heater control unit 11b, and the cooling control unit 11c includes various processors shown below. ) can be used. As described above, the various processors include, in addition to the CPU, which is a general-purpose processor that executes software and functions as various processing units, a FPGA (Field Programmable Gate Array), etc., whose circuit configuration can be changed after manufacturing. Programmable Logic Device (PLD), which is a processor, ASIC (Application Specific Integrated Circuit), etc. be

One processing unit may be configured with one of these various processors, or a combination of two or more processors of the same or different type (for example, a combination of a plurality of FPGAs and/or a CPU and combination with FPGA). Also, a plurality of processing units may be configured by one processor.

As an example of configuring a plurality of processing units with one processor, there is a form in which one processor is configured by combining one or more CPUs and software, and this processor functions as a plurality of processing units. Secondly, as typified by System On Chip (SoC), etc., there is a mode of using a processor that realizes the function of the entire system including multiple processing units with a single IC (Integrated Circuit) chip. be. In this way, various processing units are configured using one or more of the above various processors as a hardware structure.

Further, as the hardware structure of these various processors, more specifically, an electric circuit in which circuit elements such as semiconductor elements are combined can be used.

It should be noted that the above description and illustration are detailed descriptions 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 descriptions of configurations, functions, actions, and effects are descriptions of examples of configurations, functions, actions, and effects of portions related to the technology of the present disclosure. Therefore, unnecessary parts may be deleted, new elements added, or replaced with respect to the above-described description and illustration without departing from the gist of the technology of the present disclosure. Needless to say. In addition, in order to avoid complication and facilitate understanding of the portion related to the technology of the present disclosure, the descriptions and illustrations shown above require no particular explanation in order to enable implementation of the technology of the present disclosure. Descriptions of technical common sense and the like are omitted.

The disclosure of Japanese Patent Application 2020-011818 is incorporated herein by reference in its entirety.
All publications, patent applications and technical standards mentioned herein are to the same extent as if each individual publication, patent application and technical standard were specifically and individually noted to be incorporated by reference. incorporated herein by reference.

Claims (8)

A processing apparatus for performing a process of changing the temperature of a sample solution in which a sample and a processing liquid are mixed,
a plurality of first storage units into which a sample container containing the sample solution is inserted from above and to store the sample container in a surrounding state, wherein the sample solution in the sample container is heated to a first temperature; a heating block for heating;
The sample container is inserted from above and has a plurality of second storage units that surround the sample container, and the sample solution in the sample container is heated to a second temperature that is lower than the first temperature. a cooling block that cools to
a holding unit that holds a plurality of the sample containers; and a track unit that guides the holding unit with an upwardly convex inverted U-shaped track when transferring the plurality of sample containers from the heating block to the cooling block. By moving the holding part along the inverted U-shaped track, each of the plurality of sample containers is pulled upward from the first storage part, and the plurality of sample containers are pulled from above a transfer mechanism that moves downward and is inserted into each of the second accommodating portions;
A processing device having 2. The processing apparatus according to claim 1, wherein the cooling block includes a discharge section for discharging condensed water from the specimen container below the second storage section. a control unit for causing the transport mechanism to transfer the sample container to the second storage unit at a preset time after the sample container is stored in the first storage unit; 3. The processing apparatus according to claim 1 or 2. A heater for heating the heating block,
The processing apparatus according to any one of claims 1 to 3, wherein the heater has a temperature of 30°C or higher and 80°C or lower. 5. The processing apparatus according to claim 4, wherein the heater has a temperature of 60[deg.] C. or more and 80[deg.] C. or less. A cooling unit for cooling the cooling block,
The processing apparatus according to any one of claims 1 to 5, wherein the temperature of the cooling unit is 0°C or higher and 10°C or lower. The specimen solution is an object to be measured using a reagent containing a horseshoe crab blood cell extract,
7. The process according to any one of claims 1 to 6, wherein the process of changing the temperature of the sample solution by the heating block and the cooling block is a pretreatment performed before performing the measurement. Device. a processing apparatus according to any one of claims 1 to 7;
a measuring device that measures the sample solution;
measurement system.

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