Biological sample separation container, biological sample separation control device, biological sample separation control method, and biological sample separation control program

Abstract

This container (430) comprises a separation chamber (431), a recovery chamber (432), a waste liquid reservation chamber (433), a hydrophilic first flow path (434), and a hydrophilic second flow path (435). The first flow path (434) allows a specific component to move from the separation chamber (431) to the recovery chamber (432) according to the principle of siphoning when capillary force acts and centrifugal force is applied. The second flow path (435) is of a different size than the first flow path (434) and allows waste liquid to move from the separation chamber (431) to the waste liquid reservation chamber (433) according to the principle of siphoning when capillary force acts and centrifugal force is applied. The first flow path (434) is connected to a first position on a first side surface of the separation chamber (431), and the second flow path (435) is connected to a second position on a second side surface of the separation chamber (431) different from the first side surface, the first and second positions being offset in the radial direction.

Description

Technical Field

[0001] The present invention relates to a biological sample separation container and a biological sample separation control device that are set in a rotating device and used in a state where centrifugal force is applied.

Background Art

[0002] Conventionally, in order to separate specific components contained in blood (biological sample), centrifugation has been performed by putting blood or the like in a container such as a centrifuge tube. The operation of taking out and collecting specific components of the biological sample separated by such centrifugation from the container may be performed by the technique of an operator. For example, Patent Document 1 discloses a dispensing unit having a nozzle that sucks a reagent from a reagent container and discharges the reagent into a reaction container in order to improve the sealing performance of the reagent installation unit while enabling suction of the reagent by the nozzle for sample preparation, and a shutter member that opens and closes an insertion port formed in a lid portion that covers the upper portion of the reagent installation unit where the reagent container is installed.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

[0004] However, the conventional sample preparation device has the following problems. That is, in the sample preparation device disclosed in the above publication, a process of dispensing the reagent sucked from the reagent container into the reaction container containing the specimen is performed by the dispensing unit, and after reacting the specimen and the reagent in the reaction container, centrifugation is performed. Then, after centrifugation is performed and the specimen and the reagent are stirred, the supernatant in the reaction container is sucked by the nozzle.

[0005] At this time, the recovery accuracy of the supernatant depends on the accuracy of the nozzle operation and there is a possibility of variation. An object of the present invention is to provide a biological sample separation container, a biological sample separation control device, a biological sample separation control method, and a biological sample separation control program capable of suppressing the occurrence of variation in recovery accuracy when taking out and recovering a specific component of a biological sample separated by each component from a container. (Means for Solving the Problems) The biological sample separation container according to the present invention is a biological sample separation container that rotates while being set in a rotating device to recover a specific component contained in a biological sample separated by each component, and includes a separation unit, a recovery unit, a waste liquid storage unit, a hydrophilic first flow path, and a hydrophilic second flow path. The separation unit stores a biological sample and a reagent. The recovery unit is arranged radially outside the rotation center of the rotation with respect to the separation unit in a state of being set in the rotating device, and recovers a specific component of the biological sample. The waste liquid storage unit is arranged radially outside the rotation center of the rotation with respect to the separation unit in a state of being set in the rotating device, and stores waste liquid of the biological sample and the reagent excluding the specific component. The hydrophilic first flow path connects the separation unit and the recovery unit, capillary force acts, and when centrifugal force is applied by rotation, a specific component is moved from the separation unit to the recovery unit by the principle of siphon. The hydrophilic second flow path connects the separation unit and the waste liquid storage unit, capillary force different in size from the first flow path acts, and when centrifugal force is applied by rotation, the waste liquid is moved from the separation unit to the waste liquid storage unit by the principle of siphon. The first flow path is connected to a first position on a first side surface in the separation unit. The second flow path is connected at a second position on a second side surface opposite to the first side surface in the separation unit. The first position and the second position are provided at positions shifted in the radial direction in a state of being set in the rotating device. (Effects of the Invention) According to the biological sample separation container of the present invention, it is possible to suppress the occurrence of variation in recovery accuracy when taking out and recovering a specific component of a biological sample separated by each component from the container.

Brief Description of the Drawings

[0006]

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Mode for Carrying Out the Invention

[0007] (Embodiment 1) A biological sample separation device (rotating device) 10 equipped with a biological sample separation control device (control unit 20) according to an embodiment of the present invention and a biological sample separation control method will be described as follows with reference to FIGS. 1 to 9. In this embodiment, detailed descriptions that are more detailed than necessary may be omitted. For example, detailed descriptions of well-known matters and duplicate descriptions of substantially the same configuration may be omitted. This is to avoid making the following description unnecessarily redundant and to facilitate the understanding of those skilled in the art.

[0008] In addition, the applicant provides the accompanying drawings and the following description in order for those skilled in the art to fully understand the present invention, and does not intend to limit the subject matter described in the claims by these. (1) Configuration of the biological sample separation device 10 The biological sample separation device (rotating device) 10 according to this embodiment is a centrifuge used to layer blood B1 (see FIG. 6) in a container 30 so as not to mix with a specific gravity adjusting agent B2.

[0009] Here, for example, in the step of separating mononuclear cells from blood (whole blood), it is necessary to put a specific gravity adjusting agent in a centrifuge container and carefully perform the operation so that the blood and the specific gravity adjusting agent do not mix, and form a layered state. If such a process of forming a layered state of blood and a specific gravity adjusting agent is performed manually, there is a risk that each layer after blood cell separation cannot be formed well. Therefore, in the present embodiment, the control unit 20 controls the rotation of the container 30 by the biological sample separation device 10 so that an appropriate state in which blood and the specific gravity adjuster are laminated in the container 30 can be formed.

[0010] As shown in FIG. 1, the biological sample separation device 10 includes a housing unit 11, a drawer unit 12, a base member 13, a display unit 14, a power button 15, a motor (rotation driving unit) 16 (see FIG. 3), a substrate unit 17 (see FIG. 3), and a control unit (biological sample separation control device, control unit) 20 (see FIG. 4). As shown in FIG. 1, the housing unit 11 is a box-shaped member that forms the upper outer shell of the biological sample separation device 10, and an opening 11a through which the drawer unit 12 is inserted and removed and an opening 11b through which the display unit 14 is exposed are provided on the front side.

[0011] As shown in FIG. 1, the drawer unit 12 is attached in a state where it can be stored inside the housing unit 11, and as shown in FIG. 2, it shifts to a state of protruding outside the housing unit 11 by the driving force of a motor (not shown). As shown in FIG. 2, the container 30 is set in a container holding portion 12a provided on the upper surface of the drawer unit 12 in a state where the drawer unit 12 is pulled out of the housing unit 11.

[0012] For example, the container holding portion 12a is set with each container 30 so that a plurality of containers 30 are arranged radially around the rotation center O (see FIG. 2 etc.). Thereby, when the container 30 is rotated, a centrifugal force directed radially outward is applied to the blood B1 etc. held in the container 30. As shown in FIGS. 1 and 2, the base member 13 is a box-shaped member that is combined with the housing unit 11 to form the outer shell of the biological sample separation device 10, and is provided below the housing unit 11. An opening 13a for exposing the power button 15 described later is provided on the front surface of the base member 13 as shown in FIG. 3.

[0013] As shown in FIGS. 1 and 2, the display unit 14 is provided so as to be exposed on the front side of the housing unit 11, and displays various information when the power button 15 is operated to turn on the power of the biological sample separation device 10. Further, as shown in FIG. 3, the display unit 14 is provided at the end of the substrate unit 17 and is controlled by a control unit 20 (see FIG. 4) included in the substrate unit 17.

[0014] As shown in FIG. 1, the power button 15 is provided so as to be exposed on the front side of the base member 13 and is operated when turning on / off the power of the biological sample separation device 10. As shown in FIG. 3, the power button 15 is provided at the end of the substrate unit 17 in the same manner as the display unit 14, and the input of the power on / off operation is input to the control unit 20 (see FIG. 4) included in the substrate unit 17.

[0015] As shown in FIG. 3, the motor 16 is provided inside the housing unit 11 and rotates the container 30. The motor 16 rotates the container 30 set in the container holding portion 12a of the drawer portion 12 in a predetermined rotation direction at a predetermined rotation speed, and applies a centrifugal force to the blood B1 etc. stored in the container 30. Note that the biological sample separation control method using the rotation control of the container 30 by the motor 16 will be described in detail in the following section.

[0016] As shown in FIG. 3, the substrate unit 17 is attached to the upper surface of the base member 13, and the drawer portion 12 is attached in a state where it can move forward and backward. The substrate unit 17 is electrically connected to the above-described display unit 14 and power button 15, and includes a control board that controls these. The control unit (biological sample separation control device, control unit) 20 includes a CPU and a motor driver IC provided on an electric board attached to the lower surface side of the substrate unit 17 shown in FIG. 3. As shown in FIG. 4, the control unit 20 is connected to the display unit 14, the power button 15, and the motor 16. The control unit 20 switches the power state of the device by operating the power button 15. Further, the control unit 20 performs display control of the display unit 14 and rotation control of the motor 16.

[0017] (2) Configuration of Container 30 Regarding the container 30 used for separating the components of the blood B1 in the biological sample separation device 10 of the present embodiment, the following description will be given with reference to FIGS. 5 to 7. As shown in FIG. 5, the container 30 is sealed with the blood B1 and the specific gravity adjusting agent B2 respectively contained therein, and includes a first storage portion 31 for storing the blood (biological sample) B1, a second storage portion 32 for storing the specific gravity adjusting agent B2, and a hydrophobic flow path 33 connecting the first storage portion 31 and the second storage portion 32.

[0018] As shown in FIG. 6, the first storage portion 31 is arranged radially inward in a state where the container 30 is set in the container holding portion 12a of the biological sample separation device 10, and stores the blood B1. As shown in FIG. 6, the second storage portion 32 is arranged radially outside the first storage portion 31 in a state where the container 30 is set in the container holding portion 12a of the biological sample separation device 10, and stores the specific gravity adjusting agent B2 in which the blood B1 is layered.

[0019] As shown in FIG. 6, the first storage portion 31 and the second storage portion 32 are arranged along the radial direction in a state where the container 30 is set in the container holding portion 12a of the biological sample separation device 10. As shown in FIG. 5, the hydrophobic flow path 33 is a groove formed on the upper surface of the container 30 and is formed as a flow path that causes capillary action. The flow path 33 has a first end 33a connected to the inner wall 31a on the radially outer side of the first storage portion 31 and communicating with the space of the first storage portion 31, and a second end 33b connected to the inner wall on the radially inner side of the second storage portion 32 and communicating with the space of the second storage portion 32. Further, as shown in FIG. 6, the flow path 33 is arranged along the radial direction in a state where the container 30 is set in the container holding portion 12a of the biological sample separation device 10.

[0020] Here, the case where the motor 16 of the biological sample separation device 10 is rotated in a state where the blood B1 is stored in the first storage portion 31 and the specific gravity adjusting agent B2 is stored in the second storage portion 32 will be described with reference to FIG. 6. At this time, centrifugal force is applied to the blood B1 stored in the first storage part 31 of the container 30 and the specific gravity adjuster B2 stored in the second storage part 32, respectively, toward the outer side in the radial direction shown in FIG. 6.

[0021] Therefore, in the first storage part 31, the blood B1 moves toward the outer side in the radial direction and is held in a state of being collected on the inner wall 31a side on the outer side in the radial direction of the first storage part 31. Similarly, in the second storage part 32, the specific gravity adjuster B2 moves toward the outer side in the radial direction and is held in a state of being collected on the inner wall 32a side on the outer side in the radial direction of the second storage part 32. Therefore, the blood B1 is held in a state of moving to the inner wall 31a side where the first end 33a of the flow path 33 is connected. Further, the specific gravity adjuster B2 is held in a state of being collected on the inner wall 32a side, which is on the side opposite to the radially inner surface to which the flow path 33 is connected and is separated from the second end 33b of the flow path 33.

[0022] That is, when centrifugal force is applied to the container 30, the liquid interface B2a of the specific gravity adjuster B2 stored in the second storage part 32 is at a position separated from the second end 33b of the flow path 33 that connects the first storage part 31 and the second storage part 32, as shown in FIG. 6. Thereby, when the control unit 20 adjusts the rotation speed of the motor 16 to apply an appropriate centrifugal force to the blood B1, when the centrifugal force becomes greater than the capillary force of the flow path 33 for the blood B1, the blood B1 gradually moves from the first storage part 31 to the second storage part 32 through the flow path 33.

[0023] At this time, in the second storage part 32, since the specific gravity adjuster B2 is held at a position on the inner wall 32a side separated from the second end 33b of the flow path 33, the blood B1 that has moved to the second storage part 32 is layered without mixing with the specific gravity adjuster B2. Here, the relationship between the capillary force generated in the flow path 33 and the centrifugal force applied by rotating the container 30 will be described with reference to FIGS. 7(a) and 7(b).

[0024] That is, in a hydrophobic capillary flow path (flow path 33), when a certain rotation speed (centrifugal force) is reached, liquid feeding is started through the flow path 33. In the flow path 33 where the surface in contact with the blood B1 has hydrophobicity, when no centrifugal force is applied, capillary force (surface tension T) acts on the liquid. As shown in Fig. 7(a), a meniscus (a bend in the liquid surface formed by the interaction with the surface of the container) that bulges to the left in the figure is formed, and a force that holds the liquid in the flow path 33 is generated.

[0025] Then, from this state, when a centrifugal force greater than the capillary force is applied to the container 30 along the direction of the flow path 33 as shown in Fig. 7(b), the liquid (blood B1) in the flow path 33 moves radially outward by the centrifugal force. In the control unit 20 that controls the biological sample separation device 10 of the present embodiment, in the container 30 including the hydrophobic capillary flow path (flow path 33) as described above, in order to send the blood B1 from the first storage unit 31 arranged radially inward to the second storage unit 32 through the flow path 33 at an appropriate speed, rotational control is performed so that an appropriate centrifugal force is applied to the container 30.

[0026] More specifically, as shown in Fig. 8, the control unit 20 sets the rotational speed for rotating the container 30 in three stages, namely V1, V2, and V3, and controls the motor 16 so that the rotational speed gradually increases. That is, when the container 30 is set in the biological sample separation device 10 described above and the rotational control is started, the control unit 20 increases the rotational speed of the motor 16 to V1.

[0027] At this time, in the container 30, as shown in Fig. 6, due to the centrifugal force, a liquid interface B2a is formed at a position where the specific gravity adjuster B2 in the second storage unit 32 is separated from the second end of the flow path 33. At the same time, the blood B1 in the first storage unit 31 is collected by the centrifugal force toward the inner wall 31a side in the radial direction outside, and is held in the flow path 33 by the capillary force from the first end 33a of the flow path 33. Note that the rotational speed V1 is set so that the capillary force acting on the blood B1 in the flow path 33 and the centrifugal force (the first centrifugal force) generated by rotation satisfy the following relationship as shown in Fig. 8.

[0028] Capillary force > centrifugal force ·····(1) That is, the control unit 20 applies a centrifugal force smaller than the capillary force generated in the flow path 33 to control the rotational speed of the container 30 so that the blood B1 and the specific gravity adjuster B2 stay in a state where they are attracted to the radially outer surfaces in the first storage unit 31 and the second storage unit 32. The control unit 20 also has a second control for applying a centrifugal force larger than the capillary force generated in the flow path 33 to control the rotational speed of the container 30 so that the blood B1 is fed through the flow path 33.

[0029] Subsequently, when the above state stabilizes, the control unit 20 raises the rotational speed of the motor 16 to V2. At this time, inside the container 30, as shown in FIG. 8, due to a centrifugal force larger than that at the rotational speed V1, with the liquid interface B2a formed at a position away from the second end of the flow path 33 in the specific gravity adjuster B2 of the second storage unit 32, the blood B1 in the first storage unit 31 starts to be fed little by little through the flow path 33 to the second storage unit 32.

[0030] Note that, as shown in FIG. 8, the rotational speed V2 is set so that the capillary force acting on the blood B1 in the flow path 33, the centrifugal force generated by rotation (the second centrifugal force), and the centrifugal force at the time of blood cell separation satisfy the following relationship. Capillary force < centrifugal force < centrifugal force at the time of blood cell separation ·····(2) Subsequently, due to the centrifugal force applied at the rotational speed V2, the blood B1 is fed through the flow path 33 to the second storage unit 32. When the feeding of almost all the blood B1 is completed, the control unit 20 further raises the rotational speed of the motor 16 to V3.

[0031] At this time, inside the container 30, as shown in FIG. 8, during the transition from the rotational speed V2 to V3, due to a centrifugal force even larger than that at the rotational speed V2, the blood B1 in the first storage unit 31 is completely fed through the flow path 33 to the second storage unit 32. Note that, as shown in FIG. 8, the rotational speed V3 is set so that a third centrifugal force for performing blood cell separation is applied.

[0032] That is, after the above-described second control, the control unit 20 further has third control for controlling the rotation speed of the container 30 so as to rotate the container 30 at a rotation speed higher than that of the second control in a state where the blood B1 and the specific gravity adjusting agent B2 are stacked, and separating specific components contained in the blood B1. In the present embodiment, as described above, the blood B1 gradually moves from the first storage unit 31 into the second storage unit 32 through the flow path 33 where capillary force acts. When the blood B1 moves, the specific gravity adjusting agent B2 in the second storage unit 32 is held at a position away from the second end 33b of the flow path 33 through which the blood B1 is fed.

[0033] Therefore, in the second storage unit 32 where the blood B1 has moved, the blood B1 and the specific gravity adjusting agent B2 can be formed in a stacked state by appropriate liquid feeding without mixing with the specific gravity adjusting agent B2. It should be noted that the rotation speeds V1, V2, and V3 are preferably appropriately set according to various conditions such as the cross-sectional area (thickness) of the flow path 33 and the properties of the biological sample (blood) (such as clay).

[0034] Thereby, by setting an appropriate rotation speed according to various conditions, the liquid feeding speed of the blood B1 fed through the flow path 33 can be appropriately adjusted. As a result, compared with the case where the stacked state of the blood B1 and the specific gravity adjusting agent B2 is formed by human skill, variations due to human skill can be prevented, and the stacked state of the blood B1 and the specific gravity adjusting agent B2 can always be stably formed.

[0035] <Biological Sample Separation Control Method> The biological sample separation control method of the present embodiment will be described as follows with reference to the flowchart of FIG. 9. In the present embodiment, the above-described container 30 is set in the biological sample separator 10 and rotated to apply centrifugal force, so that the blood B1 stored in the first storage unit 31 of the container 30 is stacked on the specific gravity adjusting agent B2 stored in the second storage unit 32.

[0036] Specifically, in step S11, in the biological sample separation device 10 in the power-on state where the power button 15 is operated, first, as shown in FIG. 2, with the drawer part 12 of the biological sample separation device 10 pulled out, one or a plurality of containers 30 are set on the upper surface of the container holding part 12a, and then the drawer part 12 is retracted to the initial position. Next, in step S12, the control unit 20 starts the rotation of the motor 16 to rotate the container 30.

[0037] Next, in step S13, it is determined whether the rotational speed of the motor 16 has reached V1 until it reaches V1. When the rotational speed reaches V1, the process proceeds to step S14. Next, in step S14, while the container 30 is rotating at the rotational speed V1, it waits until the liquid interface of the specific gravity adjuster B2 in the second storage part 32 is formed. When the liquid interface is formed, the process proceeds to step S15.

[0038] At this time, the blood B1 in the first storage part 31 penetrates into the flow path 33 from the first end 33a of the flow path 33 and is held by capillary force (capillary force > first centrifugal force) (see FIG. 8) (first step). Note that the presence or absence of the formation of the liquid interface of the specific gravity adjuster B2 in the second storage part 32 is used as one of the conditions for determining whether the preparation for sending the blood B1 to the second storage part 32 via the flow path 33 is complete.

[0039] That is, the formation of the liquid interface of the specific gravity adjuster B2 in the second storage part 32 means that the specific gravity adjuster B2 is collected and held on the inner wall 32a on the radially outer side by centrifugal force. Therefore, in this state, even if the blood B1 is sent from the flow path 33, the second end 33b of the flow path 33 connected to the second storage part 32 is located at a position away from the liquid interface of the specific gravity adjuster B2, so that the blood B1 can be made less likely to mix with the specific gravity adjuster B2.

[0040] Next, in step S15, the control unit 20 increases the rotational speed of the motor 16 from the rotational speed V1. Next, in step S16, it is determined whether the rotational speed of the motor 16 has reached V2 until it reaches V2. When the rotational speed reaches V2, the process proceeds to step S17. Next, in step S17, when the rotational speed increases to V2, the centrifugal force increases. Therefore, since the centrifugal force becomes greater than the capillary force generated in the blood B1 within the flow path 33, the blood B1 moves to the second storage unit 32 via the flow path 33 (second step), and a state of being layered with the specific gravity adjuster B2 is formed in the second storage unit 32.

[0041] Next, in step S18, it waits until a predetermined time has elapsed after the rotational speed reaches V2. When the predetermined time has elapsed, it proceeds to step S19. Next, in step S19, the control unit 20 increases the rotational speed of the motor 16 from the rotational speed V2. Next, in step S20, while the rotational speed is increasing from V2 to V3, the movement of the blood B1 from the first storage unit 31 to the second storage unit 32 via the flow path 33 is completed.

[0042] Next, in step S21, it is determined whether the rotational speed of the motor 16 has reached V3 until it reaches V3. When the rotational speed reaches V3, the process proceeds to step S22. Next, in step S22, it waits until a predetermined time has elapsed after the rotational speed reaches V3. When the predetermined time has elapsed, it proceeds to step S23. Here, the rotational speed V3 is set so that a third centrifugal force for performing blood cell separation to separate a specific component from the blood B1 is applied.

[0043] Next, in step S23, the control unit 20 stops the rotation of the motor 16. <Main Features> The control unit (biological sample separation control device) 20 of the present embodiment controls the biological sample separation device 10 to perform a process of rotating a container 30 in which the blood B1 and the specific gravity adjusting agent B2 are placed in separate spaces to laminate the blood B1 and the specific gravity adjusting agent B2. The container 30 has a first storage unit 31 that stores the blood B1, a second storage unit 32 that stores the specific gravity adjusting agent B2, and a hydrophobic flow path 33 that connects the first storage unit 31 and the second storage unit 32 and in which capillary force acts. The biological sample separation device 10 has a container holding unit 12a that holds the container 30 such that the first storage unit 31 and the second storage unit 32 are arranged at different distances in the radial direction from the rotation center O of the rotation, and a motor 16 that rotates the container 30 around the rotation center O. The control unit 20 controls the motor 16 so as to move the blood B1 between the first storage unit 31 and the second storage unit 32 through the flow path 33 and laminate the blood B1 and the specific gravity adjusting agent B2.

[0044] Here, the blood B1 stored in the first storage unit 31 of the container 30 is sent through the hydrophobic flow path 33 to the second storage unit 32 side where the specific gravity adjusting agent B2 is stored. At this time, a force that attempts to hold the blood B1 in the flow path 33 by capillary action acts on the hydrophobic flow path 33. Thereby, by controlling the rotation speed of the container 30 to apply a centrifugal force slightly greater than the capillary force acting on the flow path 33 to the blood B1, the blood B1 can be gradually sent from the first storage unit 31 to the second storage unit 32 at an appropriate liquid feeding speed through the flow path 33 connecting the first storage unit 31 and the second storage unit 32.

[0045] As a result, it is possible to avoid the blood B1 and the specific gravity adjusting agent B2 from mixing in the container 30 and to appropriately form a laminated state. [Other Embodiments] As described above, one embodiment of the present invention has been described. However, the present invention is not limited to the above embodiment, and various modifications are possible without departing from the gist of the invention.

[0046] (A) In the above-described Embodiment 1, an example in which the present invention is realized as the control unit 20 and the biological sample separation control method mounted on the biological sample separation device 10 has been described. However, the present invention is not limited to this. For example, the present invention may be realized as a biological sample separation control program that causes a computer to execute the above-described biological sample separation control method.

[0047] This biological sample separation control program is stored in a memory (storage unit) mounted on the biological sample separation control device, and the CPU reads the biological sample separation control program stored in the memory and causes the hardware to execute each step. More specifically, by the CPU reading the biological sample separation control program and executing the above-described first step, second step, and third step S, the same effects as above can be obtained.

[0048] Further, the present invention may be realized as a recording medium storing the biological sample separation control program. (B) In the above-described Embodiment 1, as shown in FIG. 6, the flow path 33 connecting the first storage unit 31 and the second storage unit 32 is arranged along the radial direction of a circle centered on the rotation center O, and the first end 33a of the flow path 33 is connected to the inner wall 31a on the outer side in the radial direction of the first storage unit 31, and the second end 33b is connected to the surface on the inner side in the radial direction of the second storage unit 32. The configuration of the container 30 has been described as an example. However, the present invention is not limited to this.

[0049] For example, as shown in FIG. 10(a), the first end 133a of the flow path 133 connecting the first storage unit 31 and the second storage unit 32 may be connected to the inner wall 31a on the outer side in the radial direction of the first storage unit 31, and the second end 133b may be connected to the side surface of the second storage unit 32. At this time, the second end 133b of the flow path 133 connected to the second storage unit 32 may be connected to a position separated from the liquid interface and not in the liquid of the specific gravity adjusting agent B2.

[0050] (C) In the above-described Embodiment 1, as shown in FIG. 6, the first storage section 31 and the second storage section 32 each having inner walls 31a and 32a on the outer side in the radial direction were described by taking as an example the configuration of the container 30 whose inner walls are linear in plan view. However, the present invention is not limited to this. For example, as shown in FIG. 10(b), the inner walls 231a and 232a on the outer side in the radial direction of the first storage section 231 and the second storage section 232 may be curved containers 230, respectively.

[0051] In this case, when centrifugal force is applied, blood B1 tends to accumulate in the curved bottom portion of the first storage section 231, so that the amount of blood B1 remaining in the first storage section 231 can be made extremely small. Also, at this time, the flow path 233 may have a configuration of a container 230 in which the first end 233a is connected to the inner wall 231a on the outer side in the radial direction of the first storage section 231 and the second end 233b is connected to the side surface of the second storage section 232.

[0052] (D) In the above-described Embodiment 1, as shown in FIG. 6, the flow path 33 connecting the first storage section 31 and the second storage section 32 was described by taking as an example the configuration of the container 30 in which the first end 33a of the flow path 33 is connected to the inner wall 31a on the outer side in the radial direction of the first storage section 31 and the second end 33b is connected to the inner surface on the inner side in the radial direction of the second storage section 32. However, the present invention is not limited to this.

[0053] For example, as shown in FIG. 10(c), the flow path 333 may have a configuration of a container 330 in which the first end 333a is connected to the inner wall 332a on the outer side in the radial direction of the second storage section 332 and the second end 333b is connected to the inner wall 331a on the outer side in the radial direction of the first storage section 331. At this time, the specific gravity adjusting agent B2 is stored in the second storage section 332 disposed on the inner side in the radial direction of the container 330, and the blood B1 is stored in the first storage section 331 disposed on the outer side in the radial direction. Then, when centrifugal force is applied, in the container 330 in which the second end 333b is connected to the inner wall 331a on the outer side in the radial direction of the first storage section 331, the specific gravity adjusting agent B2 can be gradually superposed from the lower layer side (outer side in the radial direction) of the blood B1 in the figure.

[0054] Also, at this time, the inner walls on the radially outer sides of the first storage part 331 and the second storage part 332 may be curved as shown in FIG. 10(c) or straight as shown in FIG. 10(a) in a plan view. (E) In the above-described Embodiment 1, an example in which blood is used as a biological sample and a specific gravity adjuster is used as a reagent has been described. However, the present invention is not limited to this.

[0055] For example, the biological sample may be a sample collected from a living body other than blood, and the reagent may be a chemical agent, an additive, or the like other than the specific gravity adjuster. (F) In the above-described Embodiment 1, an example in which the flow path 33 connecting the first storage part 31 and the second storage part 32 is arranged substantially parallel in the radial direction has been described. However, the present invention is not limited to this.

[0056] For example, the flow path connecting the first storage part and the second storage part does not have to be parallel to the radial direction, and a configuration of a container arranged obliquely may be used. (G) In the above-described Embodiment 1, an example in which the first storage part 31 and the second storage part 32 are arranged along the radial direction has been described. However, the present invention is not limited to this.

[0057] For example, the first storage part and the second storage part do not have to be arranged along the radial direction, and a configuration of a container arranged obliquely may be used. (Embodiment 2) A container (biological sample separation container) 430, a control unit (biological sample separation control device) 20, and a biological sample separation control method according to another embodiment of the present invention will be described as follows with reference to FIGS. 11 to 17.

[0058] Note that components having the same functions as those in the above-described Embodiment 1 are denoted by the same reference numerals, and detailed descriptions thereof are omitted. (1) Configuration of Biological Sample Separation Device 10 The biological sample separation device (rotating device) 10 that rotationally drives the container (biological sample separation container) 430 according to this embodiment to separate specific components from the blood B1 is a centrifuge used to separate and recover a specific component (mononuclear cell layer B4) of the blood B1 from a state where the blood B1 (see FIG. 12) is layered in the container 430 so as not to be mixed with the specific gravity adjusting agent B2.

[0059] Here, for example, in the step of separating mononuclear cells from blood (whole blood), it is necessary to put a specific gravity adjusting agent into a centrifuge container and perform centrifugation from a state where the blood and the specific gravity adjusting agent are layered to separate and recover a specific component (mononuclear cell layer B4). If such a process of separating and recovering a specific component of blood is performed manually using a pipette or the like, there is a risk that the recovery of each layer may not be successful.

[0060] Therefore, in this embodiment, the control unit 20 controls the rotation of the container 430 by the biological sample separation device 10 so that a specific component (mononuclear cell layer B4) can be appropriately separated and recovered from a state where the blood B1 and the specific gravity adjusting agent are layered in the container 430. As shown in FIG. 1, the biological sample separation device 10 includes a housing portion 11, a drawer portion 12, a base member 13, a display portion 14, a power button 15, a motor (rotational drive portion) 16 (see FIG. 3), a substrate unit 17 (see FIG. 3), and a control unit (biological sample separation control device, control unit) 20 (see FIG. 4).

[0061] Note that since each configuration of the biological sample separation device 10 is the same as that in the above-described Embodiment 1, the description thereof is omitted here. (2) Configuration of the container 430 The container 430 used for separating and recovering a specific component (mononuclear cell layer B4) of the blood B1 in the biological sample separation device 10 of this embodiment will be described as follows with reference to FIGS. 11 to 13.

[0062] As shown in FIG. 11, the container 430 includes a separation chamber (separation section) 431 in which blood B1 and a specific gravity adjusting agent B2 are enclosed in a layered state, a recovery chamber (recovery section) 432 for separating and recovering a specific component (mononuclear cell layer B4) of the blood B1, etc., a waste liquid storage chamber (waste liquid storage section) 433 for storing components (waste liquid) other than the specific component (mononuclear cell layer B4) recovered in the recovery chamber 432, a hydrophilic first flow path 434 connecting the separation chamber 431 and the recovery chamber 432, and a hydrophilic second flow path 435 connecting the separation chamber 431 and the waste liquid storage chamber 433.

[0063] As shown in FIG. 11, the separation chamber 431 is disposed on the radially inner side in the container 430. As shown in FIG. 12, the separation chamber 431 contains the blood B1 and the specific gravity adjusting agent B2, and is stored in a state where the blood B1 and the specific gravity adjusting agent B2 are layered without mixing with each other. The recovery chamber (recovery section) 432 is connected to the separation chamber 431 by a hydrophilic flow path (first flow path 434) that generates capillary force, and is provided for separating and recovering a specific component (mononuclear cell layer B4) of the blood B1. As shown in FIG. 12, the recovery chamber 432 is disposed radially outside the rotation center O with respect to the separation chamber 431 in a state where the biological sample separation device 10 is set, and recovers a specific component (mononuclear cell layer B4) of the blood B1.

[0064] The waste liquid storage chamber (waste liquid storage section) 433 is connected to the separation chamber 431 by a hydrophilic flow path (second flow path 435) that generates capillary force, and is provided for recovering waste liquid of the blood B1 and the specific gravity adjusting agent B2 excluding the specific component (mononuclear cell layer B4) of the blood B1. As shown in FIG. 12, the waste liquid storage chamber 433 is disposed radially outside the rotation center O with respect to the separation chamber 431 in a state where the biological sample separation device 10 is set.

[0065] The hydrophilic first flow path 434 connects the separation chamber 431 and the recovery chamber 432 as shown in FIG. 12, and is a flow path where capillary force acts. When centrifugal force is applied by rotation in the direction of the dashed-dotted arrow in FIG. 12, the first flow path 434 moves a specific component (mononuclear cell layer B4) of the blood B1 from the separation chamber 431 to the recovery chamber 432 according to the principle of siphon.

[0066] The hydrophilic second flow path 435 connects the separation chamber 431 and the waste liquid storage chamber 433, and is a flow path where capillary force different in magnitude from that of the first flow path 434 acts. When centrifugal force is applied by rotation in the direction of the dashed-dotted arrow in FIG. 12, the second flow path 435 moves the component to be waste liquid from the separation chamber 431 to the waste liquid storage chamber 433 according to the principle of siphon.

[0067] Here, in the container 430 of the present embodiment, as described above, the capillary forces generated in the first flow path 434 and the second flow path 435 are configured to be different. Specifically, the first flow path 434 is formed such that the cross-sectional area (thickness) of the flow path is larger than that of the second flow path 435. Thereby, the capillary force generated in the second flow path 435 is larger than the capillary force generated in the first flow path 434.

[0068] Here, as shown in FIG. 12, substantially the same magnitude of centrifugal force is applied to the first flow path 434 and the second flow path 435 arranged at the same distance from the rotation center O in the radial direction. And because there is a difference in the capillary forces generated in the first flow path 434 and the second flow path 435, the timing of liquid movement through the first flow path 434 and the timing of liquid movement through the second flow path 435 can be shifted according to the change in centrifugal force. As a result, by changing the magnitude of the centrifugal force by controlling the rotational speed of the container 430, separation and recovery of a specific component (mononuclear cell layer B4) from the first flow path 434 and recovery of waste liquid from the second flow path 435 can be controlled.

[0069] Furthermore, as shown in FIG. 12, the first flow path 434 has a first end 434a connected to the separation chamber 431, a second end 434b connected to the recovery chamber 432, and a folded-back portion 434c formed between the first end 434a and the second end 434b. As shown in FIG. 12, the first end 434a is connected to the left side surface of the separation chamber 431 that is substantially parallel in the radial direction. The first end 434a is connected to a position (first position) that is displaced radially outward from the first end 435a of the second flow path 435.

[0070] As shown in FIG. 12, the second end 434b is connected to the end surface of the recovery chamber 432 that is substantially orthogonal in the radial direction. As shown in FIG. 12, the folded-back portion 434c is a bent portion provided to connect a flow path (inward flow path) that once extends radially inward after exiting the first end 434a to a flow path (outward flow path) that extends radially outward, and is provided between the first end 434a and the second end 434b.

[0071] Similarly, as shown in FIG. 12, the second flow path 435 has a first end 435a connected to the separation chamber 431, a second end 435b connected to the recovery chamber 432, and a folded-back portion 435c formed between the first end 435a and the second end 435b. As shown in FIG. 12, the first end 435a is connected to the right side surface of the separation chamber 431 that is substantially parallel in the radial direction. The first end 435a is connected to a position (second position) that is displaced radially inward from the first end 434a of the first flow path 434.

[0072] That is, the first flow path 434 is connected to the separation chamber 431 at a position (first position) that is radially outward of the second flow path 435. As shown in FIG. 12, the second end 435b is connected to the end surface of the waste liquid storage chamber 433 that is substantially orthogonal in the radial direction. As shown in FIG. 12, the folded-back portion 435c is a bent portion provided so that the flow path formed once toward the radially inner side after exiting the first end 435a faces the radially outer side, and is provided between the first end 435a and the second end 435b. As shown in FIG. 12, the folded-back portion 435c is provided at a position that is substantially symmetric about the separation chamber 431 with respect to the folded-back portion 434c on the first flow path 434 side.

[0073] Further, as shown in FIG. 12, the folded-back portion 435c on the first flow path 434 side and the folded-back portion 435c on the second flow path 435 side are arranged at positions radially inside the liquid surface where the blood B1 and the specific gravity adjuster B2 are layered in the separation and recovery process of the specific component of the blood B1 that rotates the container 430. Furthermore, in the container 430 of the present embodiment, the first position where the first flow path 434 is connected to the separation chamber 431 and the second position where the second flow path 435 is connected to the separation chamber 431 are arranged so as to sandwich the layer containing the specific component (mononuclear cell layer B4) of the blood B1 in the radial direction in a state where centrifugal force is applied (see FIG. 14(b)).

[0074] Here, the relationship between the capillary force generated in the first flow path 434 and the second flow path 435 and the centrifugal force applied by rotating the container 430 will be described with reference to FIGS. 13(a) and 13(b). That is, in the hydrophilic capillary flow paths (the first flow path 434 and the second flow path 435), when the rotation speed (centrifugal force) is lower than a certain value, liquid feeding is started through the first flow path 434 and the second flow path 435.

[0075] This is because in the first flow path 434 and the second flow path 435 whose surfaces in contact with the blood B1 have hydrophilicity, capillary force (surface tension T) acts on the liquid in a state where no centrifugal force is applied, and as shown in FIG. 13(a), a concave state is formed on the left side in the figure. In a state where centrifugal force is applied, a force for holding the liquid is generated in the first flow path 434 and the second flow path 435. Then, from this state, when the centrifugal force becomes smaller than the capillary force along the directions of the first flow path 434 and the second flow path 435 with respect to the container 430 as shown in FIG. 13(b), the liquid (blood B1) in the first flow path 434 and the second flow path 435 moves radially inward by the capillary force. Therefore, in the state where the rotation has stopped, the liquid (blood B1) in the first flow path 434 and the second flow path 435 can be fed.

[0076] In the control unit 20 that controls the biological sample separation device 10 of the present embodiment, in the container 430 including the hydrophilic capillary flow paths (the first flow path 434 and the second flow path 435) as described above, from the separation chamber 431 arranged radially inward, through the first flow path 434 and the second flow path 435, in order to feed a specific component or waste liquid to the recovery chamber 432 and the waste liquid storage chamber 433 arranged radially outward at an appropriate timing, rotational control is performed to change the magnitude of the centrifugal force applied to the container 430.

[0077] Specifically, first, when the container 430 is rotated at a predetermined rotational speed by the biological sample separation device 10, as shown in FIG. 14(a), a large centrifugal force is applied to the blood B1 and the specific gravity adjuster B2 stored in the separation chamber 431 of the container 430. At this time, the blood B1 and the specific gravity adjuster B2 are drawn to the inner wall 431a side in the radial direction outside of the separation chamber 431 by the centrifugal force and are held in a stratified state without mixing with each other. At this time, in the first flow path 434 and the second flow path 435, the liquid levels are held at substantially the same height (in the radial direction) position (refer to the dotted circle in the figure).

[0078] Next, when the rotation of the container 430 is continued at the same rotational speed (large centrifugal force) in the state of FIG. 14(a), as shown in FIG. 14(b), from the state where the blood B1 and the specific gravity adjuster B2 are stratified, blood cell separation occurs, and in order from the inside in the radial direction, plasma B3, mononuclear cell layer (specific component) B4, specific gravity adjuster B2, and red blood cell B5 are formed. Next, when the rotation speed of the container 430 is decreased to a predetermined speed, as shown in FIG. 14(c), the centrifugal force (large) applied to the liquid in the container 430 decreases to the centrifugal force (medium), so that liquid feeding is performed in the second flow path 435 on the side with a large capillary force (small cross-sectional area). At this time, in the second flow path 435, as shown in FIG. 14(c), the liquid feeding of the waste liquid (plasma B3) with the lowest specific gravity from the separation chamber 431 is performed, and the liquid level moves to the position of the connection portion (second end 435b) with the waste liquid storage chamber 433 (see the dotted circle in the figure).

[0079] Note that the relationship between the capillary force and the centrifugal force in the state of FIG. 14(c) is expressed by the following relational expression (1). Capillary force of the first flow path 434 < centrifugal force < capillary force of the second flow path 435 ····· (1) That is, the rotation speed for rotating the container 430 in the state shown in FIG. 14(c) is set to satisfy the above relational expression (1) according to the cross-sectional areas of the first flow path 434 and the second flow path 435, etc.

[0080] Next, when the rotation speed of the container 430 is increased again to a predetermined speed, as shown in FIG. 15(a), the centrifugal force (medium) applied to the liquid in the container 430 increases to the centrifugal force (large). As a result, the plasma B3 fed from the second end 435b of the second flow path 435 to the waste liquid storage chamber 433 is fed with an increased feeding speed due to the increase in the centrifugal force. Furthermore, since the inside of the flow path of the second flow path 435 is filled with liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 435a is connected in the separation chamber 431 is fed.

[0081] At this time, in the second flow path 435, as shown in FIG. 15(a), the plasma B3 up to the position radially outside the first end 435a is fed from the separation chamber 431 to the waste liquid storage chamber 433 through the second flow path 435. Thereby, most of the plasma B3 in the separation chamber 431 is fed to the waste liquid storage chamber 433.

[0082] Also, at this time, since the plasma B3 is sent to the waste liquid storage chamber 433 and the liquid level in the separation chamber 431 moves radially outward, the liquid level held in the first flow path 434 also moves to substantially the same position. Next, when the rotational speed of the container 430 is decreased again to a predetermined speed, as shown in FIG. 15(b), the centrifugal force (large) applied to the liquid in the container 430 becomes smaller to the centrifugal force (small). As a result, the remaining plasma B3 with the highest specific gravity and the mononuclear cell layer B4 left in the separation chamber 431 are sent from the second end 434b of the first flow path 434 into the recovery chamber 432.

[0083] At this time, the centrifugal force (small) applied to the liquid in the separation chamber 431 is even smaller than the centrifugal force (medium) when sending the waste liquid shown in FIG. 14(c). The relationship between the capillary force and the centrifugal force in the state of FIG. 15(b) is expressed by the following relational expression (2). Capillary force of the first flow path 434 > Centrifugal force ····· (2) That is, by controlling the rotation of the container 430 so that the centrifugal force (small) applied to the liquid in the separation chamber 431 becomes smaller than the capillary force generated in the first flow path 434, the capillary force becomes dominant. As a result, liquid feeding in the first flow path 434 is performed, and the liquid level moves to the position of the connection portion (second end 434b) with the recovery chamber 432 (see the dotted circle in the figure).

[0084] Next, when the rotational speed of the container 430 is increased again to a predetermined speed, as shown in FIG. 15(c), the centrifugal force (small) applied to the liquid in the container 430 becomes larger to the centrifugal force (large), so that the mononuclear cell layer B4 sent from the second end 434b is sent from the second end 434b into the recovery chamber 432 while increasing the liquid feeding speed due to the increase in the centrifugal force. At this time, in the first flow path 434, as shown in FIG. 15(c), the mononuclear cell layer B4, the specific gravity adjusting agent B2, etc. up to the position radially outside the first end 434a are sent from the separation chamber 431 into the recovery chamber 432 through the first flow path 434.

[0085] Note that the relationship between the capillary force and the centrifugal force in the state of Fig. 15(c) is expressed by the following relational expression (3). Capillary force of the first flow path 434 > Centrifugal force ····· (3) As a result, the liquid (such as the mononuclear cell layer B4) held in the first flow path 434 moves radially outward by the centrifugal force. Further, since the inside of the flow path of the first flow path 434 is filled with the liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 434a is connected in the separation chamber 431 is fed.

[0086] <Biological sample separation control method> In the biological separation control method of the present embodiment, as shown in Fig. 16, the control unit 20 sets the rotation speed for rotating the container 430 in three stages, namely V1, V2, and V3, and controls the motor 16 so as to change the centrifugal force applied to each component of the separated blood B1 by changing the rotation speed.

[0087] That is, with the container 430 set in the container holding portion 12a of the drawer portion 12 of the biological sample separation device 10, the control unit 20 rotates the motor 16 and increases the rotation speed up to the speed V1 as shown in Fig. 16. When the rotation speed V1 is reached, a first centrifugal force is applied to the liquid (such as blood B1) in the container 430. Then, when a predetermined time elapses in this state, blood cell separation proceeds from the state where the blood B1 and the specific gravity adjuster B2 in the separation chamber 431 are stratified (blood cell separation step).

[0088] Next, when a predetermined time has elapsed, the control unit 20 determines that the blood cell separation is completed, and as shown in Fig. 16, decreases the rotation speed of the motor 16 from V1 to V2. At this time, when the rotation speed V2 is reached, a second centrifugal force is applied to the liquid in the container 430. The relationship between the capillary force and the second centrifugal force is expressed by the above-described relational expression (1).

[0089] Capillary force of the first flow path 434 < Centrifugal force < Capillary force of the second flow path 435 ····· (1) As a result, the waste liquid (plasma B3) with the lowest specific gravity is sent out from the separation chamber 431, and as shown in FIG. 14(c), the liquid level moves to the position of the connection part (the second end 435b) with the waste liquid storage chamber 433 (see the dotted circle in the figure).

[0090] Next, as shown in FIG. 16, when the control unit 20 increases the rotation speed of the container 430 from V2 to V1 again, the centrifugal force applied to the liquid in the container 430 increases from the second centrifugal force to the first centrifugal force. As a result, the plasma B3 sent from the second end 435b of the second flow path 435 is sent while increasing the liquid sending speed due to the increase in the centrifugal force. Further, since the inside of the flow path of the second flow path 435 is filled with liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 435a is connected in the separation chamber 431 is sent out (plasma recovery step).

[0091] Next, as shown in FIG. 16, when the control unit 20 decreases the rotation speed of the container 430 from V1 to V3 again, the centrifugal force applied to the liquid in the container 430 decreases from the first centrifugal force to the third centrifugal force. As a result, the remaining plasma B3 with the highest specific gravity and the mononuclear cell layer B4 remaining in the separation chamber 431 are sent into the recovery chamber 432 from the second end 434b of the first flow path 434.

[0092] At this time, the relationship between the third centrifugal force applied to the liquid in the separation chamber 431 and the capillary force is expressed by the following relational expression (2) as described above. Capillary force of the first flow path 434 > Centrifugal force ····· (2) That is, by controlling the rotation of the container 430 so that the third centrifugal force applied to the liquid in the separation chamber 431 becomes smaller than the capillary force generated in the first flow path 434, the capillary force becomes dominant. As a result, as shown in FIG. 15(b), liquid feeding in the first flow path 434 is performed, and the liquid level moves to the position of the connection part (the second end 434b) with the recovery chamber 432 (see the dotted circle in the figure).

[0093] Next, as shown in FIG. 16, when the control unit 20 increases the rotational speed of the container 430 from V3 to V1 again, the third centrifugal force applied to the liquid in the container 430 increases to the first centrifugal force. As a result, the mononuclear cell layer B4 fed from the second end 434b is fed into the recovery chamber 432 from the second end 434b while increasing the feeding speed due to the increase in the centrifugal force (mononuclear cell layer recovery step).

[0094] Here, the biological sample separation control method of the present embodiment will be described as follows with reference to the flowchart shown in FIG. 17. That is, in step S31, in the biological sample separation device 10 in the power-on state when the power button 15 is operated, first, as shown in FIG. 2, with the drawer unit 12 of the biological sample separation device 10 pulled out, one or a plurality of containers 430 are set on the upper surface of the container holding unit 12a, and the drawer unit 12 is retracted to the initial position.

[0095] Next, in step S32, the control unit 20 starts the rotation of the motor 16 to rotate the container 430. Next, in step S33, it is determined whether or not the rotational speed of the motor 16 has reached V1 until it reaches V1. When the rotational speed reaches V1, the process proceeds to step S34. Next, in step S34, while the container 430 is rotating at the rotational speed V1, in the separation chamber 431, it waits until a predetermined time required for the blood cell separation to proceed and be completed from the state where the blood B1 and the specific gravity adjusting agent B2 are stratified (first step). Then, when the predetermined time has elapsed, the process proceeds to step S15.

[0096] Next, in step S35, the control unit 20 decreases the rotational speed of the motor 16 from the rotational speed V1. Next, in step S36, it is determined whether or not the rotational speed has decreased until the rotational speed of the motor 16 reaches V2. When the rotational speed reaches V2, the process proceeds to step S37. Next, in step S37, since the second centrifugal force applied at the rotational speed V2 is smaller than the capillary force generated in the second flow path 435, the plasma B3 is sent to the waste liquid storage chamber 433 through the second flow path 435 (second step).

[0097] Next, in step S38, the control unit 20 raises the rotational speed of the motor 16 from V2 to V1 again (third step). As a result, since the liquid feeding speed of the plasma B3 to the waste liquid storage chamber 433 through the second flow path 435 increases, the liquid feeding time is shortened. Next, in step S39, it waits until a predetermined time elapses when the liquid feeding of the plasma B3 is almost completed from inside the separation chamber 431, and when the predetermined time elapses, it proceeds to step S40.

[0098] Next, in step S40, the control unit 20 decreases the rotational speed of the motor 16 from the rotational speed V1. Next, in step S41, it is determined whether or not the rotational speed has decreased until the rotational speed of the motor 16 reaches V3. When the rotational speed reaches V3, it shifts to step S42. Next, in step S42, since the third centrifugal force applied at the rotational speed V3 is smaller than the capillary force generated in the first flow path 434, the mononuclear cell layer B4 is sent to the recovery chamber 432 through the first flow path 434 (fourth step).

[0099] In step S43, the control unit 20 raises the rotational speed of the motor 16 from V3 to V1 again (fifth step). As a result, since the liquid feeding speed of the liquid containing the mononuclear cell layer B4 to the recovery chamber 432 through the first flow path 434 increases, the liquid feeding time is shortened. Next, in step S44, it waits until a predetermined time elapses when the liquid feeding of the mononuclear cell layer B4 is almost completed from inside the separation chamber 431, and when the predetermined time elapses, it proceeds to step S45.

[0100] Next, in step S45, the control unit 20 stops the rotation of the motor 16. <Main features> The container 430 of the present embodiment rotates while being set in the biological sample separation device 10 to collect specific components contained in the separated blood B1 by component. The container 430 includes a separation chamber 431, a collection chamber 432, a waste liquid storage chamber 433, a hydrophilic first flow path 434, and a hydrophilic second flow path 435. The separation chamber 431 stores the blood B1 and the specific gravity adjuster B2. The collection chamber 432 is disposed radially outside the rotation center O with respect to the separation chamber 431 while being set in the biological sample separation device 10, and collects specific components of the blood B1. The waste liquid storage chamber 433 is disposed radially outside the rotation center O with respect to the separation chamber 431 while being set in the biological sample separation device 10, and stores waste liquid of the blood B1 and the specific gravity adjuster B2 excluding specific components. The first flow path 434 connects the separation chamber 431 and the collection chamber 432, capillary force acts, and when centrifugal force is applied, specific components are moved from the separation chamber 431 to the collection chamber 432 by the principle of the siphon. The second flow path 435 connects the separation chamber 431 and the waste liquid storage chamber 433, capillary force of a different size from that of the first flow path 434 acts, and when centrifugal force is applied, waste liquid is moved from the separation chamber 431 to the waste liquid storage chamber 433 by the principle of the siphon. The first flow path 434 is connected to the first position on the first side surface of the separation chamber 431, the second flow path 435 is connected at the second position on the second side surface opposite to the first side surface in the separation chamber 431, and the first position and the second position are provided at positions shifted in the radial direction.

[0101] That is, in the container 430 of the present embodiment, as described above, the first flow path 434 and the second flow path 435 are arranged so that the capillary force acts in the direction opposite to the vector in which the centrifugal force acts. Thereby, due to the balance between the capillary force generated in the first flow path 434 and the second flow path 435 and the centrifugal force applied by the rotation of the container 430, the liquid level height of the siphon flow path changes.

[0102] Then, the rotation speed (centrifugal force) is decreased until the condition where capillary force is dominant is achieved, and the liquid surface is held by the centrifugal force, so that the siphon channel can be made to act and liquid feeding can be performed while maintaining each layer after blood cell separation. Here, the capillary force can be controlled by the channel sizes (cross-sectional areas) of the first channel 434 and the second channel 435. Therefore, by connecting two channels (the first channel 434 and the second channel 435) with different capillary forces to the separation chamber 431 and setting them such that the siphon channel operates at different centrifugal forces, only the layer (mononuclear cell layer B4) located between the first position and the second position where the two channels (the first channel 434 and the second channel 435) are connected can be separated and recovered.

[0103] As a result, according to the configuration of the container 430, it is possible to recover liquid with the siphon channel while applying an appropriate centrifugal force, and only the component to be separated and recovered can be accurately recovered by selecting according to the specific gravity of each component obtained by separating the blood B1. [Other Embodiments] Although one embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment 2, and various modifications are possible without departing from the gist of the invention.

[0104] (A) In the above-described embodiment 2, an example in which the present invention is realized as the control unit 20 and the biological sample separation control method mounted on the biological sample separation device 10 has been described. However, the present invention is not limited to this. For example, the present invention may be realized as a biological sample separation control program that causes a computer to execute the above-described biological sample separation control method.

[0105] This biological sample separation control program is stored in a memory (storage unit) installed in a biological sample separation control device, and the CPU reads the biological sample separation control program stored in the memory and causes the hardware to execute each step. More specifically, by the CPU reading the biological sample separation control program and executing the above-described first step to fifth step, the same effects as described above can be obtained.

[0106] Further, the present invention may also be realized as a recording medium storing a biological sample separation control program. (B) In the above-described Embodiment 2, as shown in FIG. 16, when the control unit 20 performs liquid feeding while controlling the rotation of the motor 16 at the rotation speed V1, after reducing the rotation speed to the rotation speeds V2 and V3, and then raising the rotation speed to the rotation speed V1 again, an example of controlling so as to shorten the liquid feeding time was described. However, the present invention is not limited to this.

[0107] For example, as shown in FIG. 18, after the control unit 20 rotates the motor 16 at the rotation speed V1 for a predetermined time (blood cell separation step), the rotation speed is reduced to V2 to feed plasma to the waste liquid storage chamber (plasma recovery step), and the rotation speed is directly reduced to V3 to feed the mononuclear cell layer to the recovery chamber (mononuclear cell layer recovery step), the rotation of the motor 16 may be controlled. In this case, compared with the rotation control shown in FIG. 16, although the liquid feeding time becomes longer because the centrifugal force applied during liquid feeding is smaller, the same effect of being able to separate and recover a specific component (mononuclear cell layer) of blood can be obtained.

[0108] (C) In the above-described Embodiment 2, as shown in FIG. 16, an example was described in which when the control unit 20 reduces the rotation speed to V2 and V3 and the liquid feeding of the plasma B3 and the mononuclear cell layer B4 is started, the rotation speed of the motor 16 is raised to V1 again so that the first centrifugal force is applied. However, the present invention is not limited to this.

[0109] For example, the centrifugal force (rotation speed) applied to accelerate the liquid delivery does not have to be constant, and the rotation speed of the motor may be controlled so that different magnitudes of centrifugal force (rotation speed) are applied in the blood cell separation step, the plasma recovery step, and the mononuclear cell layer recovery step, respectively. (D) In the above-described Embodiment 2, as shown in FIG. 12 and the like, the container 430 in which the recovery chamber 432 is disposed on the left side in the drawing and the waste liquid storage chamber 433 is disposed on the right side in the drawing was described as an example. However, the present invention is not limited to this.

[0110] For example, a configuration of a container in which the recovery chamber and the waste liquid storage chamber are arranged in reverse left and right may be used. Even in this case, by setting the cross-sectional area (thickness) of the connected flow path to match the order of liquid delivery, that is, by setting the cross-sectional area on the recovery chamber side to be large and the cross-sectional area on the waste liquid storage chamber side to be small, the same effects as above can be obtained.

[0111] (E) In the above-described Embodiment 2, an example was described in which, since the specific gravity of the plasma B3 to be sent to the waste liquid storage chamber 433 is small, the plasma B3 is first sent to the waste liquid storage chamber 433, and then the mononuclear cell layer B4 to be recovered is sent. However, the present invention is not limited to this.

[0112] For example, when the specific gravity of the component to be waste liquid and the component to be recovered are reversed, that is, when the specific gravity of the component to be recovered is smaller than that of the component to be waste liquid, the recovery chamber and the waste liquid storage chamber may be arranged in the opposite manner to the above-described embodiment. (F) In the above-described Embodiment 2, an example in which blood is used as the biological sample and a specific gravity adjuster is used as the reagent was described. However, the present invention is not limited to this.

[0113] For example, the biological sample may be a sample collected from a living body other than blood, and the reagent may be a chemical agent, an additive, or the like other than the specific gravity adjuster. (Embodiment 3) The container (biological sample separation container) 530 according to still another embodiment of the present invention will be described as follows with reference to FIGS. 19(a) to 23.

[0114] Regarding the configuration having the same functions as those in the above-described Embodiment 1, the same reference numerals are given, and detailed descriptions thereof are omitted. Here, since each configuration of the biological sample separation device 10 is the same as that in the above-described Embodiment 1, the description thereof is omitted here. The container 530 of the present embodiment is configured by combining the upstream configuration (the first storage portion 31, the second storage portion 32, etc.) (portion A in FIG. 20(b)) in the container 30 of the above-described Embodiment 1 and the downstream configuration (the separation chamber 431, the recovery chamber 432, the waste liquid storage chamber 433, etc.) (portion B in FIG. 20(b)) in the container 430 of Embodiment 2.

[0115] The container 530 used for separating and recovering a specific component (mononuclear cell layer B4) of the blood B1 in the biological sample separation device 10 of the present embodiment will be described more specifically as follows. For convenience of explanation, it is assumed that the injection holes 537aa, 537ab and the air hole 537b are not shown in FIGS. 19(b), 20(b), 21 and 22.

[0116] As shown in FIGS. 19(a) and 19(b), the container 530 is used with its surface side covered by a cover 537. The container 530 includes a blood storage chamber (biological sample storage section) 531 that is disposed at the innermost position in the radial direction centered on the rotation center O described later and stores blood (biological sample) B1, a separation chamber (separation section) 532 in which a specific gravity adjuster B2 is enclosed, a hydrophobic flow path 533 that connects the blood storage chamber 531 and the separation chamber 532, a recovery chamber (recovery section) 536a that separates and recovers specific components (mononuclear cell layer B4) of the blood B1, a waste liquid storage chamber (waste liquid storage section) 536b that stores components (waste liquid) excluding the specific components (mononuclear cell layer B4) recovered in the recovery chamber 536a, a hydrophilic first flow path 534 that connects the separation chamber 532 and the recovery chamber 536a, and a hydrophilic second flow path 535 that connects the separation chamber 532 and the waste liquid storage chamber 536b.

[0117] As shown in FIG. 19(b), the blood storage chamber (biological sample storage section) 531 is disposed at the innermost position in the radial direction of the container 530 and encloses blood B1 (see FIG. 21(a)). The blood B1 stored in the blood storage chamber 531 is injected through an injection hole 537aa provided in the cover 537 as shown in FIG. 20(a). As shown in FIG. 19(b), the separation chamber 532 is disposed adjacent to the blood storage chamber 531 on the outer side in the radial direction. The separation chamber 532 encloses a specific gravity adjuster B2 (see FIG. 21(a)). The specific gravity adjuster B2 stored in the separation chamber 532 is injected through an injection hole 537ab provided in the cover 537 as shown in FIG. 20(a).

[0118] In addition, in the multi-layer liquid feeding process described later, blood B1 is fed from the blood storage chamber 531 to the separation chamber 532, and the separation chamber 532 stores the blood B1 and the specific gravity adjuster B2 in a state where they are multi-layered without mixing with each other (see FIG. 21(b)). The blood storage chamber 531 and the separation chamber 532 are arranged along the radial direction in a state where the container 530 is set in the container holding portion 12a of the biological sample separation device 10 as shown in FIG. 20(b).

[0119] The hydrophobic flow path 533 is a groove formed on the upper surface of the container 530 and is formed as a flow path that causes capillary action. The flow path 533 has a first end 533a connected to the inner wall 531a on the outer side in the radial direction of the blood storage chamber 531 and communicating with the space of the blood storage chamber 531, and a second end 533b connected to the inner wall on the inner side in the radial direction of the separation chamber 532 and communicating with the space of the separation chamber 532. Also, as shown in FIG. 20(b), the flow path 533 is arranged along the radial direction in a state where the container 530 is set in the container holding portion 12a of the biological sample separation device 10.

[0120] Here, the case where the motor 16 of the biological sample separation device 10 is rotated in a state where the blood B1 is stored in the blood storage chamber 531 and the specific gravity adjuster B2 is stored in the separation chamber 532 will be described with reference to FIGS. 21(a) and 21(b). At this time, centrifugal force is applied to the blood B1 stored in the blood storage chamber 531 of the container 530 and the specific gravity adjuster B2 stored in the separation chamber 532, respectively, toward the outer side in the radial direction shown in FIG. 20(b).

[0121] Therefore, in the blood storage chamber 531, the blood B1 moves toward the outer side in the radial direction and is held in a state of being collected on the inner wall 531a side on the outer side in the radial direction of the blood storage chamber 531. Similarly, in the separation chamber 532, the specific gravity adjuster B2 moves toward the outer side in the radial direction and is held in a state of being collected on the inner wall 532a side on the outer side in the radial direction of the separation chamber 532. Therefore, the blood B1 is held in a state of moving to the inner wall 531a side where the first end 533a of the flow path 533 is connected. Also, the specific gravity adjuster B2 is held in a state of being collected on the inner wall 532a side, which is on the opposite side of the surface on the inner side in the radial direction to which the flow path 533 is connected and is separated from the second end 533b of the flow path 533.

[0122] That is, when centrifugal force is applied to the container 530, the liquid interface B2a of the specific gravity adjuster B2 stored in the separation chamber 532 is at a position separated from the second end 533b of the flow path 533 connecting the blood storage chamber 531 and the separation chamber 532, as shown in FIG. 21(a). Accordingly, when the control unit 20 adjusts the rotational speed of the motor 16 to apply an appropriate magnitude of centrifugal force to the blood B1, when the centrifugal force becomes greater than the capillary force of the flow path 533, the blood B1 gradually moves from the blood storage chamber 531 through the flow path 533 to the separation chamber 532.

[0123] At this time, in the separation chamber 532, since the specific gravity adjuster B2 is held at a position on the inner wall 532a side separated from the second end 533b of the flow path 533, the blood B1 that has moved into the separation chamber 532 is stratified without mixing with the specific gravity adjuster B2. Here, the relationship between the capillary force generated in the flow path 533 and the centrifugal force applied by rotating the container 530 is as described with reference to FIGS. 7(a) and 7(b) in the above-described Embodiment 1.

[0124] That is, in the hydrophobic capillary flow path (flow path 533), when a certain rotational speed (centrifugal force) is reached, liquid feeding is started through the flow path 533. This is because in the flow path 533 whose surface in contact with the blood B1 has hydrophobicity, in a state where no centrifugal force is applied, capillary force (surface tension T) acts on the liquid, and as shown in FIG. 7(a), a meniscus (a bend in the liquid surface formed by the interaction with the surface of the container) that bulges to the left in the figure is formed, and a force for holding the liquid in the flow path 533 is generated.

[0125] Then, when a centrifugal force greater than the capillary force is applied to the container 530 along the direction of the flow path 533 as shown in FIG. 7(b) from this state, the liquid (blood B1) in the flow path 533 moves radially outward by the centrifugal force. In the control unit 20 that controls the biological sample separation apparatus 10 of the present embodiment, in the container 530 including the hydrophobic capillary flow path (flow path 533) as described above, in order to send the blood B1 from the blood storage chamber 531 disposed radially inward to the separation chamber 532 through the flow path 533 at an appropriate speed, rotational control is performed so that an appropriate centrifugal force is applied to the container 530.

[0126] The recovery chamber (recovery unit) 536a is connected to the separation chamber 532 by a hydrophilic flow path (first flow path 534) that generates capillary force, and is provided for separating and recovering specific components (such as the mononuclear cell layer B4 (see Fig. 22(d))) of the blood B1. As shown in Fig. 20(b), the recovery chamber 536a is disposed radially outside the rotation center O with respect to the separation chamber 532 in the state of being set in the biological sample separation apparatus 10, and recovers specific components (mononuclear cell layer B4) of the blood B1.

[0127] The waste liquid storage chamber (waste liquid storage unit) 536b is connected to the separation chamber 532 by a hydrophilic flow path (second flow path 535) that generates capillary force, and is provided for recovering specific components (plasma B3) of the blood B1. As shown in Fig. 20(b), the waste liquid storage chamber 536b is disposed radially outside the rotation center O with respect to the separation chamber 532 in the state of being set in the biological sample separation apparatus 10.

[0128] The hydrophilic first flow path 534 connects the separation chamber 532 and the recovery chamber 536a as shown in Fig. 20(b), and is a flow path where capillary force acts. When centrifugal force is applied by rotation in the direction of the dashed-dotted arrow in Fig. 20(b), the first flow path 534 moves specific components (mononuclear cell layer B4) of the blood B1 and a part of the specific gravity adjusting agent B2 from the separation chamber 532 to the recovery chamber 536a according to the principle of siphon.

[0129] The hydrophilic second flow path 535 connects the separation chamber 532 and the waste liquid storage chamber 536b, and is a flow path where capillary forces of different magnitudes act compared to the first flow path 534. When centrifugal force is applied by rotation in the direction of the dashed-dotted arrow in Fig. 20(b), the second flow path 535 transfers the component (plasma B3) that becomes waste liquid from the separation chamber 532 to the waste liquid storage chamber 536b according to the siphon principle.

[0130] Here, in the container 530 of the present embodiment, as described above, the capillary forces generated in the first flow path 534 and the second flow path 535 are configured to have a difference. Specifically, the first flow path 534 is formed such that the cross-sectional area (thickness) of the flow path is larger than that of the second flow path 535. As a result, the capillary force generated in the second flow path 535 is larger than the capillary force generated in the first flow path 534.

[0131] Here, as shown in Fig. 20(b), the same magnitude of centrifugal force is applied to the first flow path 534 and the second flow path 535 arranged at the same distance from the rotation center O in the radial direction. And due to the difference in the capillary forces generated in the first flow path 534 and the second flow path 535, the timing of the liquid movement through the first flow path 534 and the timing of the liquid movement through the second flow path 535 can be shifted according to the change in the centrifugal force. As a result, by changing the magnitude of the centrifugal force by controlling the rotation speed of the container 530, the separation and recovery of a specific component (mononuclear cell layer B4) from the first flow path 534 and the recovery of the waste liquid from the second flow path 535 can be controlled.

[0132] Furthermore, as shown in Fig. 20(b), the first flow path 534 has a first end 534a connected to the separation chamber 532, a second end 534b connected to the recovery chamber 536a, and a folded-back portion 534c formed between the first end 534a and the second end 534b. As shown in Fig. 20(b), the first end 534a is connected to the left side surface in the separation chamber 532 that is substantially parallel to the radial direction. The first end 534a is connected to a position (first position) shifted radially outward from the first end 535a of the second flow path 535.

[0133] As shown in FIG. 20(b), the second end 534b is connected to an end face that is substantially orthogonal to the radial direction in the recovery chamber 536a. As shown in FIG. 20(b), the folded-back portion 534c is a bent portion provided so as to connect a flow path (inward flow path) once formed toward the inside in the radial direction after exiting the first end 534a to a flow path (outward flow path) toward the outside in the radial direction, and is provided between the first end 534a and the second end 534b.

[0134] Similarly, as shown in FIG. 20(b), the second flow path 535 has a first end 535a connected to the separation chamber 532, a second end 535b connected to the recovery chamber 536a, and a folded-back portion 535c formed between the first end 535a and the second end 535b. As shown in FIG. 20(b), the first end 535a is connected to the right side surface that is substantially parallel to the radial direction in the separation chamber 532. The first end 535a is connected to a position (second position) that is shifted radially inward from the first end 534a of the first flow path 534.

[0135] That is, the first flow path 534 is connected to the separation chamber 532 at a position (first position) that is radially outside the second flow path 535. As shown in FIG. 20(b), the second end 535b is connected to an end face that is substantially orthogonal to the radial direction in the waste liquid storage chamber 536b. As shown in FIG. 20(b), the folded-back portion 535c is a bent portion provided so as to go out from the first end 535a and then go toward the outside in the radial direction after once forming a flow path toward the inside in the radial direction, and is provided between the first end 535a and the second end 535b. As shown in FIG. 20(b), the folded-back portion 535c is provided at a position that is substantially symmetric about the separation chamber 532 with respect to the folded-back portion 534c on the first flow path 534 side.

[0136] Further, as shown in Fig. 20(b), the folded portion 534c on the first flow path 534 side and the folded portion 535c on the second flow path 535 side are arranged at positions radially inside the liquid surface where the blood B1 and the specific gravity adjusting agent B2 are superposed in the separation and recovery process of the specific components of the blood B1 that rotates the container 530. Furthermore, in the container 530 of the present embodiment, the first position where the first flow path 534 is connected to the separation chamber 532 and the second position where the second flow path 535 is connected to the separation chamber 532 are arranged so as to sandwich the layer containing the specific component (mononuclear cell layer B4) of the blood B1 in the radial direction in a state where centrifugal force is applied (see Fig. 21(c)).

[0137] Here, the relationship between the capillary force generated in the first flow path 534 and the second flow path 535 and the centrifugal force applied by rotating the container 530 will be described with reference to Figs. 21(b) and 21(c). That is, in the hydrophilic capillary flow paths (the first flow path 534 and the second flow path 535), when the rotation speed (centrifugal force) is lower than a certain value, the liquid feeding starts through the first flow path 534 and the second flow path 535.

[0138] This is because in the first flow path 534 and the second flow path 535 whose surfaces in contact with the blood B1 have hydrophilicity, when no centrifugal force is applied, capillary force (surface tension T) acts on the liquid, and as shown in Fig. 13(a) described in the second embodiment, a concave state is formed on the left side in the figure. When centrifugal force is applied, a force for holding the liquid in the first flow path 534 and the second flow path 535 is generated.

[0139] Then, from this state, when the centrifugal force becomes smaller than the capillary force along the directions of the first flow path 534 and the second flow path 535 with respect to the container 530 as shown in Fig. 13(b), the liquid (blood B1) in the first flow path 534 and the second flow path 535 moves radially inward by the capillary force. Therefore, in a state where the rotation has stopped, the liquid (blood B1) in the first flow path 534 and the second flow path 535 can be fed.

[0140] In the control unit 20 that controls the biological sample separation device 10 of the present embodiment, in the container 530 including the hydrophilic capillary flow paths (the first flow path 534 and the second flow path 535) as described above, from the separation chamber 532 arranged on the radially inner side, through the first flow path 534 and the second flow path 535, in order to send a specific component or waste liquid to the recovery chamber 536a and the waste liquid storage chamber 536b arranged on the radially outer side at an appropriate timing, rotation control is performed so as to change the magnitude of the centrifugal force applied to the container 530.

[0141] Specifically, first, when the container 530 is rotated at a predetermined rotational speed by the biological sample separation device 10, as shown in FIG. 21(b), a large centrifugal force is applied to the blood B1 and the specific gravity adjuster B2 stored in the separation chamber 532 of the container 530. At this time, the blood B1 and the specific gravity adjuster B2 are drawn to the inner wall 532a side on the radially outer side of the separation chamber 532 by the centrifugal force and are held in a state of being layered without mixing with each other. At this time, in the first flow path 534 and the second flow path 535, the liquid levels are held at substantially the same height (in the radial direction).

[0142] Next, when the rotation of the container 530 is continued at the same rotational speed (large centrifugal force) in the state of FIG. 21(b), as shown in FIG. 21(c), from the state where the blood B1 and the specific gravity adjuster B2 are layered, blood cells are separated, and layers of plasma B3, mononuclear cell layer (specific component) B4, specific gravity adjuster B2, and red blood cells B5 are formed in order from the radially inner side. Next, when the rotational speed of the container 530 is decreased to a predetermined speed, as shown in FIG. 22(a), the large centrifugal force applied to the liquid in the container 530 becomes a medium centrifugal force, so that liquid feeding is performed in the second flow path 535 on the side with a large capillary force (small cross-sectional area). At this time, in the second flow path 535, as shown in FIG. 22(a), the waste liquid (plasma B3) with the smallest specific gravity in the separation chamber 532 is fed, and the liquid level moves to the position of the connection portion (the second end 535b) with the waste liquid storage chamber 536b (see the circled mark in FIG. 22(a)).

[0143] Note that the relationship between the capillary force and the centrifugal force in the state of Fig. 22(a) is expressed by the following relational expression (1’). Capillary force of the first flow path 534 < centrifugal force < capillary force of the second flow path 535 ····· (1’) That is, the rotational speed for rotating the container 530 in the state shown in Fig. 22(a) is set to satisfy the above relational expression (1’) according to the cross-sectional areas of the first flow path 534 and the second flow path 535, etc.

[0144] Next, when the rotational speed of the container 530 is increased again to a predetermined speed, as shown in Fig. 22(b), the centrifugal force (medium) applied to the liquid in the container 530 increases to the centrifugal force (large). As a result, the plasma B3 sent from the second end 535b of the second flow path 535 to the waste liquid storage chamber 536b is sent at an increased liquid sending speed due to the increase in the centrifugal force. Further, since the inside of the flow path of the second flow path 535 is filled with liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 535a is connected in the separation chamber 532 is sent.

[0145] At this time, in the second flow path 535, as shown in Fig. 22(b), the plasma B3 up to the position radially outside the first end 535a is sent from the inside of the separation chamber 532 to the waste liquid storage chamber 536b through the second flow path 535. As a result, most of the plasma B3 in the separation chamber 532 is sent to the waste liquid storage chamber 536b.

[0146] Also, at this time, since the plasma B3 is sent to the waste liquid storage chamber 536b and the liquid level in the separation chamber 532 moves radially outward, the liquid level held in the first flow path 534 also moves to substantially the same position (see the circled mark in Fig. 22(b)). Next, when the rotational speed of the container 530 is decreased again to a predetermined speed, the centrifugal force (large) applied to the liquid in the container 530 decreases to the centrifugal force (small). At this time, in the first flow path 534, the specific gravity adjuster B2 and the mononuclear cell layer B4 remaining in the separation chamber 532 are sent from the first end 534a to the second end 534b of the first flow path 534 (see the circled mark in Fig. 22(c)).

[0147] At this time, the centrifugal force (small) acting on the liquid in the separation chamber 532 is even smaller than the centrifugal force (medium) when sending the waste liquid shown in FIG. 21(c). And the relationship between the capillary force and the centrifugal force in this state is represented by the following relational expression (2’). Capillary force of the first flow path 534 > centrifugal force ····· (2’) That is, by controlling the rotation of the container 530 so that the centrifugal force (small) acting on the liquid in the separation chamber 532 becomes smaller than the capillary force generated in the first flow path 534, the capillary force becomes dominant. Thereby, liquid feeding in the first flow path 534 is performed, and the liquid level moves to the position of the connection portion (the second end 534b) with the recovery chamber 536a.

[0148] Next, when the rotation speed of the container 530 is increased again to a predetermined speed, as shown in FIG. 22(d), the centrifugal force (small) applied to the liquid in the container 530 increases to the centrifugal force (large), so that the mononuclear cell layer B4 fed from the second end 534b is fed into the recovery chamber 536a from the second end 534b while increasing the liquid feeding speed due to the increase in the centrifugal force. At this time, in the first flow path 534, as shown in FIG. 22(d), the mononuclear cell layer B4, the specific gravity adjuster B2, etc. up to the position radially outside the first end 534a are fed from the inside of the separation chamber 532 into the recovery chamber 536a through the first flow path 534.

[0149] Note that the relationship between the capillary force and the centrifugal force in the state of FIG. 22(d) is represented by the following relational expression (3’). Capillary force of the first flow path 534 < centrifugal force ····· (3’) Thereby, the liquid (such as the mononuclear cell layer B4) held in the first flow path 534 moves radially outward by the centrifugal force. Further, since the inside of the flow path of the first flow path 534 is filled with liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 534a is connected in the separation chamber 532 is fed.

[0150] <Biological sample separation control method> In the biological separation control method of this embodiment, as shown in FIG. 23, the control unit 20 sets the rotation speed for rotating the container 530 in five levels, namely V1, V2, V3, V4, and V5, and controls the motor 16 so that by changing the rotation speed, the centrifugal force applied to each component of the separated blood B1 is changed.

[0151] That is, with the container 530 set in the container holding portion 12a of the drawer portion 12 of the biological sample separation device 10, the control unit 20 rotates the motor 16 and raises the rotation speed to the speed V1 as shown in FIG. 23. At this time, inside the container 530, due to the centrifugal force, a liquid interface B2a is formed at a position where the specific gravity adjuster B2 in the separation chamber 532 is away from the second end 533b of the flow path 533 (formation of the interface of the specific gravity adjuster B2). At the same time, the blood B1 in the blood storage chamber 531 is collected toward the inner wall 531a on the radially outer side by the centrifugal force and is held in the flow path 533 by capillary force from the first end 533a of the flow path 533.

[0152] Note that as shown in FIG. 23, the rotation speed V1 is set so that the capillary force acting on the blood B1 in the flow path 533 and the centrifugal force generated by the rotation satisfy the following relational expression (3). Capillary force > Centrifugal force ·····(3) That is, the control unit 20 performs a first control for controlling the rotation speed of the container 530 so that a centrifugal force smaller than the capillary force generated in the flow path 533 is applied and the blood B1 and the specific gravity adjuster B2 stay in a state of being attracted to the radially outer surfaces in the blood storage chamber 531 and the separation chamber 532, and a second control for controlling the rotation speed of the container 530 so that a centrifugal force larger than the capillary force generated in the flow path 533 is applied and the blood B1 is sent through the flow path 533.

[0153] Subsequently, when the above state stabilizes, the control unit 20 raises the rotation speed of the motor 16 to V2. At this time, inside the container 530, as shown in FIG. 23, with a centrifugal force greater than that at the rotation speed V1, the liquid interface B2a is formed at a position away from the second end 533b of the flow path 533 for the specific gravity adjuster B2 in the separation chamber 532, and the blood B1 in the blood storage chamber 531 starts to be gradually fed into the separation chamber 532 through the flow path 533 (start of multi-layer liquid feeding).

[0154] Note that as shown in FIG. 23, the rotation speed V2 is set such that the capillary force acting on the blood B1 in the flow path 533, the centrifugal force generated by rotation, and the centrifugal force during blood cell separation satisfy the following relational expression (4). Capillary force < Centrifugal force < Centrifugal force during blood cell separation ·····(4) Subsequently, due to the centrifugal force applied at the rotation speed V2, the blood B1 is fed into the separation chamber 532 through the flow path 533. When the feeding of most of the blood B1 is completed, the control unit 20 further increases the rotation speed of the motor 16 to V3.

[0155] At this time, inside the container 530, as shown in FIG. 23, before the rotation speed shifts from V2 to V3, due to a centrifugal force even greater than that at the rotation speed V2, the blood B1 in the blood storage chamber 531 is completely fed into the separation chamber 532 through the flow path 533 (complete transfer of the blood B1). Note that as shown in FIG. 23, the rotation speed V3 is set such that a centrifugal force for performing blood cell separation is applied.

[0156] When the rotation speed V3 is reached, a first centrifugal force is applied to the liquid (such as blood B1) inside the container 530. And when a predetermined time elapses in this state, blood cell separation proceeds from the state where the blood B1 and the specific gravity adjuster B2 in the separation chamber 532 are stratified (blood cell separation process). Next, when a predetermined time has elapsed, the control unit 20 determines that the blood cell separation is completed, and as shown in FIG. 23, decreases the rotation speed of the motor 16 from V3 to V4.

[0157] At this time, when the rotational speed V4 is reached, a second centrifugal force is applied to the liquid in the container 530. The relationship between the capillary force and the second centrifugal force is represented by the above-described relational expression (1’). The capillary force of the first flow path 534 < centrifugal force < the capillary force of the second flow path 535 ····· (1’) As a result, the waste liquid (plasma B3) with the lowest specific gravity is sent out from the separation chamber 532, and the liquid level moves to the position of the connection portion (second end 535b) with the waste liquid storage chamber 536b.

[0158] Next, as shown in FIG. 23, when the control unit 20 increases the rotational speed of the container 530 from V4 to V3 again, the centrifugal force applied to the liquid in the container 530 increases from the second centrifugal force to the first centrifugal force. As a result, the plasma B3 sent from the second end 535b of the second flow path 535 is sent while increasing the liquid feeding speed due to the increase in the centrifugal force. Further, since the inside of the flow path of the second flow path 535 is filled with liquid, the siphon phenomenon acts, and all the liquid up to the position where the first end 535a is connected in the separation chamber 532 is sent (plasma recovery step).

[0159] Next, as shown in FIG. 23, when the control unit 20 decreases the rotational speed of the container 530 from V3 to V5 again, the centrifugal force applied to the liquid in the container 530 decreases from the first centrifugal force to the third centrifugal force. As a result, the specific gravity adjuster B2 and the mononuclear cell layer B4 remaining in the separation chamber 532 are sent from the first end 534a to the second end 534b of the first flow path 534. At this time, the relationship between the third centrifugal force applied to the liquid in the separation chamber 532 and the capillary force is represented by the following relational expression (2’) as described above.

[0160] The capillary force of the first flow path 534 > centrifugal force ····· (2’) That is, by controlling the rotation of the container 530 so that the third centrifugal force acting on the liquid in the separation chamber 532 is smaller than the capillary force generated in the first flow path 534, the capillary force becomes dominant. As a result, liquid feeding in the first flow path 534 is performed, and the liquid level moves to the position of the connection portion (second end 534b) with the recovery chamber 536a.

[0161] Next, as shown in FIG. 23, when the control unit 20 increases the rotation speed of the container 530 from V5 to V1 again, the third centrifugal force applied to the liquid in the container 530 becomes as large as the first centrifugal force. As a result, the mononuclear cell layer B4 fed from the second end 534b is fed into the recovery chamber 536a from the second end 534b while increasing the liquid feeding speed due to the increase in the centrifugal force (mononuclear cell layer recovery step).

[0162] <Appendix 1> The biological sample separation control device according to the first disclosure is a biological sample separation control device that controls the rotation device to rotate a container in which a biological sample and a reagent are placed in separate spaces so as to perform a process of laminating the biological sample and the reagent, wherein the container has a first storage portion for storing the biological sample, a second storage portion for storing the reagent, and a hydrophobic flow path that connects the first storage portion and the second storage portion and in which capillary force acts, the rotation device has a container holding portion that holds the container so that the first storage portion and the second storage portion are arranged at different distances in the radial direction from the rotation center of the rotation, and a rotation driving portion that rotates the container around the rotation center, and includes a control unit that controls the rotation driving unit so as to move the biological sample or the reagent through the flow path between the first storage portion and the second storage portion and laminate the biological sample and the reagent.

[0163] <Appendix 2> The biological sample separation control device according to the second disclosure is the biological sample separation control device according to the first disclosure, In a state where the container is set in the container holding part, the flow path is arranged along the radial direction.

[0164] <Appendix 3> The biological sample separation control device according to the third disclosure is the biological sample separation control device according to the first or second disclosure, The control unit controls the rotation driving unit so as to apply a centrifugal force greater than the capillary force generated in the flow path by the rotation of the rotating device.

[0165] <Appendix 4> The biological sample separation control device according to the fourth disclosure is the biological sample separation control device according to the third disclosure, The control unit has a first control for controlling the rotational speed of the container so that a centrifugal force smaller than the capillary force generated in the flow path is applied and the biological sample and the reagent stay in a state where they are attracted to the radially outer surfaces in the first storage part and the second storage part, and a second control for controlling the rotational speed of the container so that a centrifugal force greater than the capillary force generated in the flow path is applied and the biological sample or the reagent is fed through the flow path.

[0166] <Appendix 5> The biological sample separation control device according to the fifth disclosure is the biological sample separation control device according to the fourth disclosure, The control unit further has a third control for controlling the rotational speed of the container so that, after the second control, the container is rotated at a rotational speed greater than the second control in a state where the biological sample and the reagent are layered, and a specific component contained in the biological sample is separated.

[0167] <Appendix 6> The biological sample separation control device according to the sixth disclosure is the biological sample separation control device according to the fourth or fifth disclosure, In the second control, the control unit controls the moving speed of the biological sample or the reagent by adjusting the rotational speed by the rotation driving unit.

[0168] <Appendix 7> The biological sample separation control device according to the seventh disclosure is the biological sample separation control device according to any one of the first to sixth disclosures, and in a state where the container is set in the container holding part, the first storage part is arranged closer to the rotation center side in the radial direction than the second storage part.

[0169] <Appendix 8> The biological sample separation control device according to the eighth disclosure is the biological sample separation control device according to the seventh disclosure, and when a centrifugal force greater than the capillary force generated in the flow path is applied by the rotation of the rotating device, the biological sample moves from the first storage part to the second storage part through the flow path.

[0170] <Appendix 9> The biological sample separation control device according to the ninth disclosure is the biological sample separation control device according to the seventh or eighth disclosure, and in a state where a centrifugal force is applied to the container by the rotating device, the connection part between the flow path and the second storage part is arranged closer to the rotation center side than the liquid interface of the reagent.

[0171] <Appendix 10> The biological sample separation control device according to the tenth disclosure is the biological sample separation control device according to any one of the seventh to ninth disclosures, and when a centrifugal force is applied to the container by the rotating device, in the second storage part arranged on the outer side in the radial direction, the reagent is held in a state of being drawn to the outer surface in the radial direction.

[0172] <Appendix 11> The biological sample separation control device according to the eleventh disclosure is the biological sample separation control device according to any one of the first to tenth disclosures, and in a state where the container is set in the container holding part, the flow path has a first end connected to the first storage part and a second end connected to the second storage part, the first end is connected to the outer surface in the radial direction in the first storage part, The second end is connected to the radially inner surface in the second reservoir.

[0173] <Appendix 12> The biological sample separation control device according to the 12th disclosure is a biological sample separation control device according to any one of the 1st to 10th disclosures, In a state where the container is set in the container holding part, the flow path has a first end connected to the first reservoir and a second end connected to the second reservoir, The first end is connected to the radially outer surface in the first reservoir, The second end is connected radially inward of the liquid level of the reagent in a state where centrifugal force is applied on the surface along the radial direction of the second reservoir.

[0174] <Appendix 13> The biological sample separation control device according to the 13th disclosure is a biological sample separation control device according to any one of the 1st to 10th disclosures, The first reservoir is arranged radially inward of the second reservoir and has a first wall surface arranged radially outward and connected to the flow path, The first wall surface has a concave surface where the connection portion with the flow path is arranged most radially outward.

[0175] <Appendix 14> The biological sample separation control device according to the 14th disclosure is a biological sample separation control device according to any one of the 1st to 10th disclosures, The second reservoir is arranged radially inward of the first reservoir, The flow path is connected to the second reservoir on the radially outer surface and connected to the first reservoir on the radially outer surface.

[0176] <Appendix 15> The biological sample separation control method according to the 15th disclosure is a biological sample separation control method by the biological sample separation control device described in any one of the 1st to 14th disclosures, A first step of controlling the rotation driving unit so that the biological sample stored in the first storage unit and the reagent stored in the second storage unit remain in a state where they are each brought close to the radially outer surface in the first storage unit and the second storage unit; A second step of controlling the rotation driving unit so that the biological sample or the reagent moves from the first storage unit to the second storage unit or from the second storage unit to the first storage unit through the flow path at a rotation speed; A third step of controlling the rotation driving unit so that the biological sample is separated into specific components in a state where the biological sample and the reagent are layered due to the movement of the biological sample or the reagent in the second step at a rotation speed; and is provided with.

[0177] <Appendix 16> The biological sample separation control program according to the 16th disclosure causes a computer to execute the biological sample separation control method according to the 15th disclosure.

Industrial Applicability

[0178] The biological sample separation container of the present invention has the effect of being able to suppress the occurrence of variations in recovery accuracy when taking out and recovering specific components of a biological sample separated into each component from the container, and thus can be widely applied to various containers used for separating biological samples.

Explanation of Signs

[0179] 10 Biological sample separation device (rotation device) 11 Housing part 11a, 11b Openings 12 Drawer part 12a Container holding part 13 Base member 13a Opening 14 Display part 15 Power button 16 Motor (rotation driving unit) 17 Substrate unit 20 Control unit (biological sample separation control device, control unit) 30 Container 31 First storage section 31a Inner wall 32 Second storage section 32a Inner wall 33 Flow path 33a First end 33b Second end 130 Container 133 Flow path 133a First end 133b Second end 230 Container 231 First storage section 231a Inner wall 232 Second storage section 232a Inner wall 233 Flow path 233a First end 233b Second end 330 Container 331 First storage section 331a Inner wall 332 Second storage section 332a Inner wall 333 Flow path 333a First end 333b Second end 430 Container (biological sample separation container) 431 Separation chamber (separation section) 431a Inner wall 432 Recovery chamber (recovery section) 433 Waste liquid storage chamber (waste liquid storage section) 434 First flow path 434a First end 434b Second end 434c Folding section 435 Second flow path 435a First end 435b Second end 435c Folding section 530 Container (biological sample separation container) 531 Blood storage chamber (blood storage section) 531a Inner wall 532 Separation Chamber (Separation Section) 532a Inner Wall 533 Flow Path 533a First End 533b Second End 534 First Flow Path 534a First End 534b Second End 534c Folding Portion 535 Second Flow Path 535a First End 535b Second End 535c Folding Portion 536a Recovery Chamber (Recovery Section) 536b Waste Liquid Storage Chamber (Waste Liquid Storage Section) 537 Cover 537aa Injection Hole 537ab Injection Hole 537b Air Hole B1 Blood (Biological Sample) B2 Specific Gravity Adjusting Agent (Reagent) B2a Liquid Interface B3 Plasma B4 Mononuclear Cell Layer (Specific Component) B5 Red Blood Cells O Rotation Center

Claims

1. A biological sample separation container that rotates while being set in a rotating device to collect a specific component contained in a biological sample separated by component, comprising: a separation unit for storing a biological sample and a reagent; a recovery unit that is disposed radially outside the rotation center of the rotation with respect to the separation unit while being set in the rotating device, and that recovers a specific component of the biological sample; a waste liquid storage unit that is disposed radially outside the rotation center of the rotation with respect to the separation unit while being set in the rotating device, and that stores the waste liquid of the biological sample and the reagent excluding the specific component; a hydrophilic first flow path that connects the separation unit and the recovery unit, exerts capillary force, and moves the specific component from the separation unit to the recovery unit by the principle of siphon when centrifugal force is applied by the rotation; a hydrophilic second flow path that connects the separation unit and the waste liquid storage unit, exerts capillary force different in magnitude from that of the first flow path, and moves the waste liquid from the separation unit to the waste liquid storage unit by the principle of siphon when centrifugal force is applied by the rotation; and comprising: the first flow path is connected to a first position on a first side surface in the separation unit; the second flow path is connected at a second position on a second side surface opposite to the first side surface in the separation unit; the first position and the second position are provided at positions shifted in the radial direction while being set in the rotating device; the capillary force generated in the second flow path is greater than the capillary force generated in the first flow path; the first position and the second position are arranged so as to sandwich a layer containing the specific component in the radial direction in a state where the centrifugal force is applied; the second flow path is connected to a side surface of the separation unit at a position radially inside the first flow path; a biological sample separation container.

2. The second flow path has a smaller cross-sectional area than the first flow path. The biological sample separation container according to Claim 1.

3. While being set in the rotating device, the first flow path and the second flow path include an inward flow path that extends radially inward from a connection portion to the separation unit, a folding portion that folds back from the inward flow path so as to extend radially outward, and an outward flow path that extends radially outward through the folding portion and is connected to the recovery unit and the waste liquid storage unit, respectively. The biological sample separation container according to Claim 1 or 2.

4. The folding portion is provided at a position radially inside the liquid levels of the biological sample and the reagent in the separation portion in a state where the centrifugal force is applied. The biological sample separation container according to claim 3.

5. A biological sample storage portion that is disposed inside in the radial direction centered on the rotation center with respect to the separation portion and stores a biological sample, A capillary flow path that connects the biological sample storage portion and the separation portion, further comprising: The biological sample separation container according to claim 1.

6. A biological sample separation control device that controls the rotation of a rotating device in which the biological sample separation container according to claim 1 or 2 is set, comprising a rotation control portion that controls a drive portion of the rotating device, The rotation control portion, A first mode in which the drive portion of the rotating device is rotated at a first speed so that the biological sample and the reagent are stored while being brought close to the radially outer surface in the separation portion, When the biological sample is separated in the separation portion in the first mode, the drive portion of the rotating device is rotated at a second speed smaller than the first speed, and the waste liquid is sent to the waste liquid storage portion through the second flow path. A second mode, having: When the waste liquid is sent to the waste liquid storage portion in the second mode, the rotation control portion rotates the drive portion of the rotating device at a third speed greater than the second speed, and the waste liquid is sent to the waste liquid storage portion until the waste liquid in the separation portion disappears. Further having a third mode to be made, When the feeding of the waste liquid to the waste liquid storage portion is completed in the third mode, the rotation control portion rotates the drive portion of the rotating device at a fourth speed smaller than the third speed, and the specific component is sent from the separation portion to the recovery portion through the first flow path. Further having a fourth mode, When the specific component is sent to the recovery portion in the fourth mode, the rotation control portion rotates the drive portion of the rotating device at a fifth speed greater than the fourth speed, and the specific component is sent to the recovery portion until the specific component in the separation portion disappears. Further having a fifth mode to be made, Biological sample separation control device.

7. As a stage before the first mode, the rotation control unit is disposed inside in the radial direction centered on the rotation center with respect to the separation unit, and from a biological sample storage unit that stores a biological sample, through a capillary flow path that connects the biological sample storage unit and the separation unit, the biological sample is fed into the separation unit, and the biological sample separation container is rotated so that the reagent and the biological sample are layered in the separation unit. The biological sample separation control device according to claim 6.

8. A biological sample separation control method for controlling the rotation of a rotating device in which the biological sample separation container according to claim 1 or 2 is set, A first step of rotating a driving unit of the rotating device at a first speed so that the biological sample and the reagent are stored while being brought close to the radially outer surface in the separation unit; When the biological sample is separated in the separation unit in the first step, a second step of rotating the driving unit of the rotating device at a second speed smaller than the first speed and feeding the waste liquid into the waste liquid storage unit through the second flow path; When the waste liquid is fed into the waste liquid storage unit in the second step, a third step of rotating the driving unit of the rotating device at a third speed larger than the second speed and feeding the waste liquid into the waste liquid storage unit until the waste liquid disappears from the separation unit; When the feeding of the waste liquid into the waste liquid storage unit is completed in the third step, a fourth step of rotating the driving unit of the rotating device at a fourth speed smaller than the third speed and feeding the specific component from the separation unit into the recovery unit through the first flow path; When the specific component is fed into the recovery unit in the fourth step, a fifth step of rotating the driving unit of the rotating device at a fifth speed larger than the fourth speed and feeding the specific component into the recovery unit until the specific component disappears from the separation unit; A biological sample separation control method comprising the above.

9. As a stage before the first step, a step of feeding the biological sample into the separation unit from a biological sample storage unit that is disposed inside in the radial direction centered on the rotation center with respect to the separation unit and stores the biological sample, through a capillary flow path that connects the biological sample storage unit and the separation unit, and rotating the biological sample separation container so that the reagent and the biological sample are layered in the separation unit is further provided. The biological sample separation control method according to claim 8.

10. A biological sample separation control program that causes a computer to execute the biological sample separation control method according to Claim 8. ​

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