JP7848006B2 - Sample preparation apparatus, sample processing apparatus, sample preparation method, and sample processing method - Google Patents

Description

This invention relates to a sample preparation apparatus, a sample processing apparatus, a sample preparation method, and a sample processing method.

Patent Document 1 discloses a sample preparation apparatus equipped with a centrifuge. In this sample preparation apparatus described in Patent Document 1, the user performs the task of setting the centrifuge tube into the centrifuge.

Japanese Patent Publication No. 2021-162321

In the above-mentioned Patent Document 1, the user is required to manually set the centrifuge tube in the centrifuge, therefore there is room for improvement from an automation standpoint.

One objective of this invention is to achieve further automation of sample preparation apparatus equipped with a centrifuge.

To achieve the above objective, the sample preparation apparatus (100) according to the first invention is a sample preparation apparatus (100) for preparing a measurement sample from a specimen, comprising: a holding unit (20) for holding a centrifuge tube (12); a transfer unit (40) for transferring the centrifuge tube (12) held by the holding unit (20); a dispensing unit (60) for dispensing the specimen into the centrifuge tube (12) before or after transfer by the transfer unit (40); and a centrifugation unit (30) for holding the centrifuge tube (12) transferred by the transfer unit (40) and centrifugating the specimen dispensed into the centrifuge tube by rotating it. The holding unit (20) includes a first holding unit (10a) for holding a plurality of sample containers (11) and a second holding unit (10b) for holding a plurality of centrifuge tubes (12). The transfer unit (49) returns the centrifuge tubes (12) containing samples prepared from samples in the sample containers (11) held in the first position of the first holding unit (10a) to the corresponding first position of the second holding unit (10b) after centrifugation, and returns the centrifuge tubes (12) containing samples prepared from samples in the sample containers (11) held in the second position of the first holding unit (10a) to the corresponding second position of the second holding unit (10b) after centrifugation.

The sample preparation apparatus (100) according to the first invention includes a transfer unit (40) for transferring the centrifuge tube (12) between the holding unit (20) and the centrifuge unit (30), as described above. Since the transfer unit (40) can transfer the centrifuge tube (12) to the centrifuge unit (30), the user's task of setting the centrifuge tube (12) into the centrifuge unit (30) is reduced, achieving further automation.

The sample preparation method according to the second invention comprises: transferring centrifuge tubes (12) placed in a holding unit (20) by the user to a centrifuge unit (30); dispensing a sample into the centrifuge tubes (12) transferred to the centrifuge unit (30); centrifuging the sample contained in the centrifuge tubes (12) using the centrifuge unit (30); and returning the centrifuged centrifuge tubes (12) to the holding unit (20) . The holding unit (20) includes a first holding unit (10a) for holding a plurality of sample containers (11) and a second holding unit (10b) for holding a plurality of centrifuge tubes (12). In the step of returning the centrifuge tube (12) after centrifugation to the holding unit (20), the centrifuge tube (12) containing the sample prepared from the sample in the sample container (11) held in the first position of the first holding unit (10a) is returned to the corresponding first position of the second holding unit (10b), and the centrifuge tube (12) containing the sample prepared from the sample container (11) held in the second position of the first holding unit (10a) is returned to the corresponding second position of the second holding unit (10b).

According to the sample preparation method of the third invention, the user's task of setting the centrifuge tube (12) into the centrifuge unit (30) can be reduced, achieving further automation.

According to the present invention, further automation of sample preparation involving centrifugation can be achieved. Furthermore, according to the present invention, the container transport mechanism can be simplified and the apparatus can be miniaturized.

This is a schematic diagram showing an overview of the first configuration example of a sample preparation device. This is a perspective view showing the transport mechanism of the sample preparation device. This is a cross-sectional view along the line III-III in Figure 2. This is a diagram showing the case of a centrifuge tube. This is a schematic diagram showing the transfer section of the sample preparation device. This is a first plan view showing the lid of the centrifugal separation section of the sample preparation apparatus. This is a second plan view showing the lid of the centrifugal separation section of the sample preparation apparatus. This is a third plan view showing the lid of the centrifugal separation section of the sample preparation apparatus. This is a diagram illustrating a specific example of sample preparation procedures. This diagram shows the movement of the rack when transferring centrifuge tubes using a sample preparation device. This diagram shows the movement of the rack when dispensing samples using a sample preparation device. This diagram shows the movement of the rack during processing by the processing unit of the sample preparation device. This diagram shows the movement of the rack after processing by the processing unit of the sample preparation device. This is a flowchart illustrating the operation process of the sample preparation device. This is a schematic diagram illustrating an overview of other configuration examples for the sample preparation apparatus. This diagram shows the rotary table used when samples are dispensed by the sample preparation device and processed by the processing unit. This diagram shows the rotary table used when processing samples in the centrifugal separation section of the sample preparation device.

The embodiments will be described below with reference to the drawings.

[Overview of Sample Preparation Equipment]
First, with reference to Figure 1, an overview of the sample preparation apparatus 100 as a sample processing apparatus according to one embodiment will be described.

The sample preparation device 100 is a device that prepares a measurement sample for measurement by flow cytometry by pre-treating a blood sample. The measurement sample is a sample of leukocytes derived from a blood sample that has been immunostained. More specifically, a measurement sample is prepared in which the cell surface antigens (e.g., CD4, CD25, CD62L) and intracellular antigens (e.g., FOXP3) of T cells contained in the blood sample are labeled with a labeled antibody.

Figure 1 is a schematic plan view showing the configuration of the sample preparation device 100. As shown in Figure 1, the sample preparation device 100 includes a rack transport unit (holding unit) 20 located on the front side of the device (Y1 direction side). The rack transport unit 20 includes a rack 10a for holding multiple processing containers 11, a rack 10b for holding multiple centrifuge tubes 12, and a rack 10c for holding multiple sample containers 13 containing blood samples. The rack transport unit 20 includes a container transport mechanism 22. The racks 10a to 10c are spaced apart along the Y-axis so that the rows of containers they hold are aligned along the X-axis, that is, the longitudinal direction of the racks is aligned along the X-axis. In the embodiment shown in Figure 1, each rack is fixed to the rack transport unit 20 so that it cannot be removed. The user sets the containers 11 to 13 in each rack fixed to the rack transport unit 20.

The rack transport unit 20 includes a common drive unit 21a that moves racks 10a to 10c integrally along the X direction.

The rack transport unit 20 includes a rack 10a that holds the processing container 11 and a rack 10b that holds the centrifuge tube (reaction vessel) 12, with a magnet 23 positioned between them. As described later, the magnet 23 is used to collect magnetization from the composite formed in the processing container 11, which contains red blood cells and magnetic particles (solid phase).

The sample preparation apparatus 100 includes a centrifugal separation unit 30. The centrifugal separation unit 30 includes a rotor 31 that rotates at high speed and a plurality of holder units 32 provided on the outer circumference of the rotor 31. The holder units 32 have, for example, a cylindrical shape and are capable of receiving and holding the centrifugal tube 12 inside. Furthermore, when the rotor 31 stops, the holder units 32 hold the centrifugal tube 12 in a position with its opening facing upwards.

The sample preparation apparatus 100 includes a transfer unit 40 that transfers the centrifuge tube 12 between the rack transfer unit 20 and the centrifugation unit 30. The transfer unit 40 is supported on a transfer shaft 41 so as to be movable in the Y direction. Furthermore, the transfer unit 40 is movable in the Z direction (vertical direction).

The sample preparation device 100 includes a dispensing unit 50. The dispensing unit 50 is supported on a common transfer axis 41, shared with the transfer unit 40, so as to be movable in the Y direction. The dispensing unit 50 is also movable in the Z direction (vertical direction). The dispensing unit 50 is equipped with a pipette 50a, which is used to dispense the sample contained in the sample container 13 into the processing container 11.

The sample preparation device 100 includes a stirring unit 51 for agitating the blood sample. The stirring unit 51 grasps the sample container 13, removes it from the rack 10c, and agitates the blood sample inside the sample container 13 by inverting and stirring it.

The sample preparation device 100 includes a dispensing unit 60. The dispensing unit 60 is supported on a transfer shaft 61 so as to be movable in the X direction. The transfer shaft 61 is also supported on a transfer shaft 62 so as to be movable in the Y direction. This allows the dispensing unit 60 to move horizontally within the device. Furthermore, the dispensing unit 60 is movable in the Z direction (vertical direction). The dispensing unit 60 is equipped with a pipette 60a and uses the pipette 60a to dispense reagents placed in the reagent placement section 70a and reagent placement section 70b into the processing container 11 of the rack transport section 20 or into the centrifuge tube 12 in the centrifuge section 30. The dispensing unit 60 further aspirates the supernatant from the processing container 11, where magnetic particles have been magnetized by the magnet 23, and dispenses it into the centrifuge tube 12 transferred to the centrifuge section 30. The dispensing unit 60 then discharges the reagent to the processing container 11, which has been moved to the reagent discharge position by the drive unit 21a.

The sample preparation device 100 includes reagent storage sections 70a and 70b. Reagent storage section 70a includes a refrigerator and maintains the reagents at a low temperature. Reagent storage section 70b maintains the reagents at room temperature.

The sample preparation device 100 includes a nozzle cleaning unit 80. The nozzle cleaning unit 80 cleans the nozzle of the dispensing unit 60.

The sample preparation apparatus 100 includes a control unit 90 that controls each part of the apparatus. The control unit 90 includes a processor and a storage unit. The processor is, for example, composed of a CPU. The storage unit may include memory and storage. The processor controls each part of the sample preparation apparatus 100 by executing a program stored in the storage unit.

The reagent storage section 70a includes a lid and a shutter member. The reagent storage section 70a is a box-shaped member with a lid that can be opened and closed. The lid is provided to cover the upper part of the reagent storage section 70a. The lid has multiple insertion holes for nozzles, positioned above the multiple reagent containers. The shutter member is positioned to overlap the lid. The shutter member has nozzle insertion holes and a shielding portion. The shutter member is provided on the lid so as to open and close integrally with the lid.

In the layout of the sample preparation apparatus 100 shown in Figure 1, the parts that the user accesses to operate the apparatus, specifically the reagent placement sections 70a and 70b and the initial positions (see Figure 10) where containers are set in the racks 10a to 10c held in the rack transport section 20, are concentrated on the right side of the apparatus (X1 direction side). In particular, the initial position of the rack transport section 20, which the user frequently accesses, is located at the front (Y1 direction side) on the right side (X1 direction side), while the centrifugation section 30 is located at the back (Y2 direction side) on the left side (X2 direction side). In other words, the centrifugation section 30 and the rack transport section 20 are separated by a predetermined distance, and the layout is designed to reduce the frequency with which the user needs to approach the centrifugation section 30. Since the rotor 31 of the centrifugation section 30 rotates at high speed, it is preferable to keep the user away from it as much as possible to improve safety. The sample preparation apparatus 100 allows the centrifuge tube 12 to be set in the centrifugation section 30 by the transfer section 40, eliminating the need for the user to access the centrifugation section 30. Furthermore, by positioning the rack transport section 20, which users access to set the centrifuge tubes 12 into the device, away from the centrifugal separation section 30, the possibility of users accidentally bringing their hands too close to the operating centrifugal separation section 30 is further reduced.

The rack transport unit 20 will be described with reference to Figures 2 and 3. Figure 2 is a perspective view of the rack transport unit 20 from the rear (Y2 direction). The rack transport unit 20 comprises an upper portion 220 including a base 21b on which racks 10a to 10c are installed, and a lower portion 230 provided below the upper portion 220, which generates and transmits the driving force for moving the racks 10a to 10c. The upper portion 220 and the lower portion 230 are arranged with a space between them vertically, separated by a sheet metal 231 on the left side (X1 direction) and a sheet metal 232 on the right side (X2 direction).

The lower portion 230 of the rack transport section 20 includes a drive unit 21a consisting of a motor, a pair of pulleys 212a, and a belt 212. The output shaft of the drive unit 21a is connected to the pulley 212a on the left side (X1 direction side). The belt 212 extends along the X axis, and both ends are stretched across the pair of pulleys 212a. A connecting member 213 is fixed to the belt 212. The connecting member 213 is connected to a slider 214. The slider 214 is movable in the X direction along a rail 215.

Figure 3 is a cross-sectional view of the rack transport section 20 in Figure 2, taken along the line III-III. The slider 214 includes a side wall portion 214a provided on the Y1 direction side and extending upward, and a side wall portion 214b provided on the Y2 direction side and also extending upward. The base 21b is provided with slits 210 and 211 extending along the X axis. The side wall portion 214a protrudes upward from below the base 21b through the slit 210. The side wall portion 214b protrudes upward from below the base 21b through the slit 211.

The upper end portion of the side wall 214a protruding from the slit 210 is connected to a fastener 221 that is screwed to the bottom 10c1 of the rack 10c. The upper end portion of the side wall 214b protruding from the slit 211 is connected to the fastener 221 screwed to the bottom 10c1 of the rack 10c, to the fastener 222 screwed to the bottom 10b1 of the rack 10b, and to the fastener 223 screwed to the bottom 10a1 of the rack 10a.

In this configuration, when the drive unit 21a drives the side walls 214a and 214b of the slider 214 through the slits 210 and 211 in the X-axis direction, the racks 10a to 10c connected to the side walls 214a and 214b move integrally in the X-axis direction. In this embodiment, the slider 214 and racks 10a to 10c of the rack transport unit 20 are fixed by fasteners 221, 222, and 223 using screws. However, any configuration that allows the movement of the slider 214 and the racks 10a to 10c to interlock is acceptable; screw fastening is not essential. For example, a downwardly convex projection on the bottom of the racks 10a to 10c and a hole in the upper end of the side walls 214a and 214b could engage with each other.

As shown in Figures 2 and 3, the centrifuge tube 12 is set in the rack 10b while housed in its case 12a. The transfer unit 40, described later, is configured to remove the centrifuge tube 12, along with its case 12a, from the rack 10b and transfer it to the centrifugal separation unit 30.

Figure 4 is a front view of case 12a. Case 12a has a notch 121 and flanges 122 and 123. Case 12a is made of a thermally conductive metal material, such as aluminum. By forming case 12a from a material with high thermal conductivity, the controlled temperature in the centrifuge section 30 is transmitted to the sample in the centrifuge tube 12, making temperature control of the sample easier. The notch 121 allows a reading unit (not shown) to read identification information such as barcodes or two-dimensional codes attached to the side of the centrifuge tube 12 while it is housed in case 12a. The flanges 122 and 123 function as catches to prevent case 12a from falling off when the transfer section 40 grasps and transfers it.

The configuration of the transfer unit 40 will be explained with reference to Figure 5. Figure 5 is a perspective view showing the configuration of the transfer unit 40. In Figure 5, for clarity of explanation, parts that move together are shown with the same hatching. Additionally, hatching is applied to the centrifuge tube 12 to make its position clearer.

The transfer unit 40 is mounted on the sheet metal 41A that constitutes the transfer shaft 41, so as to be movable along the Y and Z axes. A Y-axis motor 415 is mounted on the sheet metal 41A. A belt 414 is stretched across the output shaft of the Y-axis motor 415. A horizontally extending rail 411a is also mounted on the sheet metal 41A. A sheet metal 411 is slidably mounted on the rail 411a. A portion of the sheet metal 411 is fixed to the belt 414 by fasteners 413. As a result, the belt is driven by the Y-axis motor 415, and the sheet metal 411 moves along the Y axis accordingly.

A sheet metal 417 is attached to the sheet metal 411 to support a component involved in Z-axis movement, which will be described later. The sheet metal 417 is a vertically elongated plate extending in the vertical direction, and a Z-axis motor 416 is attached to the lower back surface (X1 direction side) of the sheet metal 417. An opening/closing motor 420 is positioned above the sheet metal 417. A rail 418 extending in the vertical direction is attached to the front surface (X2 direction side) of the sheet metal 417. The output of the Z-axis motor 416 is transmitted to a belt 412 that is stretched vertically. A sheet metal 431 is fixed to the belt 412. The sheet metal 431 is slidably attached to the rail 418. The sheet metal 431 has a rail 433 extending in the horizontal direction. A sliding part 432 is slidably attached to the rail 433. The sliding portion 432 is biased in the Y2 direction along the rail 433 by a spring member 440 horizontally positioned between the sheet metal 431 and the sliding portion 432, as indicated by the white arrow in Figure 5.

A first gripping portion 434, which constitutes one of a pair of gripping portions that grip the upper part of the centrifuge tube 12, is attached to the lower end of the slide portion 432 on the Y1 direction side. As shown in Figure 5, the slide portion 432 and the first gripping portion 434 are illustrated with the same hatching, and these parts move as a single unit. That is, when the slide portion 432 moves in the Y1 direction, as will be described later, the first gripping portion 434 also moves in the Y1 direction. The second gripping portion 435, which constitutes the other gripping portion, is fixed to the sheet metal 431 mentioned earlier. In other words, the first gripping portion 434 is movable in the Y1 direction relative to the second gripping portion 435, which is fixed to the sheet metal 431.

The rear end (Y2 direction side) of the sliding portion 432 is provided with a contact portion 432a that is thicker in the X2 direction. The opening/closing motor 420, located above the sheet metal 417, has its output shaft connected to the belt 421. When the driving force of the opening/closing motor 420 is transmitted to the belt 421, the first rod 423, which extends vertically to the sheet metal 417 and is rotatable around its axis, rotates. Both the upper and lower ends of the first rod 423 are connected to a second rod 424 that extends parallel and vertically to the first rod 423. When the first rod 423 rotates around its axis, the second rod 424 rotates around the first rod 423, as shown by the arrows in Figure 5. Note that a portion of the sheet metal 431, specifically the portion between the Y2 direction end fixed to the belt 412 and the portion slidably fixed to the rail 418, extends between the first rod 423 and the second rod 424.

When the second rod 424 rotates around the first rod 423, the contact portion 432a of the slide portion 432 is pushed in the Y1 direction by the second rod 424. As a result, the slide portion 432 moves in the Y1 direction against the biasing force of the spring member 440. As described earlier, the slide portion 432 and the first gripping portion 434 move together, and as the first gripping portion 434 moves in the Y1 direction, the gap between the first gripping portion 434 and the second gripping portion 435 opens, allowing the centrifuge tube 12 to be gripped.

The Z-axis motor 416 is connected to a pair of gripping parts 434 and 435 via a belt 412, a sheet metal 431, and a sliding part 432. When the Z-axis motor 416 is driven, the sheet metal 431, which is fixed to the belt 412, moves vertically. As the sheet metal 431 moves vertically, the gripping parts 434 and 435 move vertically along the Z-axis.

When moving the centrifuge tube 12 from the rack transport unit 20 to the centrifugal separation unit 30, the Z-axis motor 416 and the opening/closing motor 420 lower the gripping parts 434 and 435 to grip the centrifuge tube 12 in the rack transport unit 20, and then move the gripped centrifuge tube 12 upwards. The gripping parts 434 and 435, which are gripping the centrifuge tube 12, are then moved above the centrifugal separation unit 30 by the Y-axis motor 415. Once above the centrifugal separation unit 30, the Z-axis motor 416 lowers the centrifuge tube 12, and the centrifuge tube 12 is inserted into the holder part 32 of the centrifugal separation unit 30. The opening/closing motor 420 opens the gripping parts 434 and 435, releasing the grip. When returning the centrifuge tube 12 containing the sample prepared in the centrifugal separation unit 30 to the rack transport unit 20, the reverse operation is performed. Specifically, the Z-axis motor 416 and the opening/closing motor 420 lower the gripping parts 434 and 435 to grip the centrifuge tube 12 in the centrifugal separation unit 30, and then move the gripped centrifuge tube 12 upwards. The gripping parts 434 and 435, holding the centrifuge tube 12, are then moved above the rack transport unit 20 by the Y-axis motor 415. Once above the rack transport unit 20, the Z-axis motor 416 lowers the centrifuge tube 12, and it is inserted into its original holding position on the rack 10b of the rack transport unit 20. The opening/closing motor 420 opens the gripping parts 434 and 435, releasing the grip.

When the centrifuge tube 12 is returned from the centrifuge unit 30 to the rack transport unit 20, the prepared sample is contained within the centrifuge tube 12. Therefore, it is necessary to prevent the centrifuge tube 12 from falling out during transport to prevent the sample from spilling into the apparatus. To address this, the transport unit 40 shown in Figure 5 has a spring member 440 that biases the gripping parts 434 and 435 in a direction that closes them together. This allows the gripping parts 434 and 435 to maintain a closed state even without motor drive force, thus preventing the centrifuge tube 12 from falling out during transport even if the opening/closing motor 420 malfunctions.

Furthermore, in the transfer unit 40 shown in Figure 5, the opening/closing motor 420 is mounted on the sheet metal 417 so that it does not need to move along the Z-axis. The driving force of the opening/closing motor 420 is transmitted to the sliding unit 432 by the rotation of vertically extending rods 423 and 424. This structure is advantageous in that it allows for weight reduction of the elements that move along the Z-axis. In other words, in the structure of this transfer unit 40, the only elements that move along the Z-axis for the transfer of the centrifuge tube 12 are the sheet metal 431, the sliding unit 432, and the pair of gripping units 434 and 435. Since there is no need to move heavy parts such as the opening/closing motor 420 along the Z-axis, the load on the Z-axis motor 416 can be reduced, and the possibility of failure due to wire breakage of the Z-axis motor 416 can be reduced. Also, even if a malfunction occurs in the Z-axis motor 416, the weight reduction prevents the centrifuge tube 12 from falling along with the gripping units 434 and 435 during transfer.

The sample preparation apparatus 100, equipped with a transfer unit 40 with this configuration, can transfer the centrifuge tubes 12 set on the rack 10b of the rack transfer unit 20 to the rotor 31 of the centrifuge unit 30. Therefore, the user does not need to access the centrifuge unit 30. This achieves greater operational automation compared to conventional techniques where the user must set the centrifuge tubes 12 in the centrifuge unit 30. Furthermore, restricting user access to the centrifuge unit 30 improves safety.

Referring to Figures 6 to 8, the lid 34 covering the top of the centrifuge unit 30 will be described. As shown in Figure 6, the centrifuge unit 30 is covered from above by a cover 33. The cover 33 is provided with openings 331 and 332. Opening 331 is used when inserting and removing the centrifuge tube 12 into and from the centrifuge unit 30. Opening 332 is used when dispensing reagents into the centrifuge tube 12 within the centrifuge unit 30 or when aspirating a sample from the centrifuge tube 12. Opening 331 has a larger area than the centrifuge tube 12 because it needs to pass through the centrifuge tube 12 and the transfer unit 40. Opening 332 has a smaller area than the centrifuge tube 12 because it only needs to pass through the nozzle.

A lid 34 is provided above the cover 33 to close the openings 331 and 332. The lid 34 is slidable horizontally (in the Y direction). The lid 34 has an opening 341 and a notch 342. The lid 34 is moved in the Y direction by a drive unit 35.

As shown in Figure 6, the lid 34 closes both the opening 331 and the opening 332 of the cover 33 by moving in the Y1 direction. Specifically, the lid 34 covers the upper part of the opening 331. Also, the opening 332 of the cover 33 is covered by the opening 341 of the lid 34 shifting in the Y1 direction relative to the opening 332 of the cover 33. The lid 34 remains closed, as shown in Figure 6, except during normal operation, i.e., when the centrifuge tube 12 is being transferred by the transfer unit 40 or when samples/reagents are being dispensed by the dispensing unit 60.

Furthermore, as shown in Figure 7, the lid 34 moves in the Y2 direction, opening both the opening 331 and the opening 332 of the cover 33. Specifically, the Y1-side end of the lid 34 is moved further towards the Y2 direction than the Y2-side end of the opening 331 of the cover 33. Also, the notch 342 of the lid 34 is positioned to correspond to the opening 332 of the cover 33, opening the opening 332. The lid 34 takes the position with the opening 331 open as shown in Figure 7 when the transfer unit 40 sets the centrifuge tube 12 on the rotor 31, and when the transfer unit 40 removes the centrifuge tube 12 from the rotor 31. The operation when setting the centrifuge tube 12 is as follows: First, before the lid 34 opens, the rotor 31 rotates and stops so that the holder part 32 on which the centrifuge tube 12 is set is positioned below the opening 331. When the transfer unit 40, which is gripping the centrifuge tube 12, is positioned above the centrifugal separation unit 30, the lid 34 moves to the state shown in Figure 7, opening the opening 331. Once the centrifuge tube 12 is set by the transfer unit 40, the lid 34 returns to the state shown in Figure 6, closing the opening 331. The operation for removing the centrifuge tube 12 is as follows: First, before the lid 34 opens, the rotor 31 rotates and stops so that the holder unit 32, which holds the centrifuge tube 12 to be removed, is positioned below the opening 331. Once the transfer unit 40 is positioned above the centrifugal separation unit 30, the lid 34 moves to the state shown in Figure 7, opening the opening 331. Once the centrifuge tube 12 is removed by the transfer unit 40, the lid 34 returns to the state shown in Figure 6, closing the opening 331. In this way, the lid 34 opens only when the transfer unit 40 is accessing the centrifugal separation unit 30, preventing the user from accidentally putting their hand into the centrifugal separation unit 30 and improving safety. Furthermore, the inside of the centrifuge section 30 is maintained at a constant temperature suitable for the reaction between the sample and reagent. Therefore, by opening the lid 34 only when necessary, temperature fluctuations inside the centrifuge section 30 are minimized. Additionally, since the rotation of the rotor 31 always stops when the opening 331 is opened by the lid 34, safety is further enhanced.

Furthermore, as shown in Figure 8, the lid 34 moves slightly in the Y2 direction, closing the opening 331 of the cover 33 while opening the opening 332 of the cover 33. Specifically, the lid 34 covers the upper part of the opening 331. Also, the opening 341 of the lid 34 is positioned to correspond to the opening 332 of the cover 33, and the opening 332 is opened. When the transfer unit 40 dispenses a sample or reagent into the centrifuge tube 12 held by the holder unit 32, the lid 34 takes the position shown in Figure 8 with the opening 332 open. The operation when dispensing a sample or reagent is as follows: First, before the lid 34 opens, the rotor 31 rotates and stops so that the holder unit 32 holding the centrifuge tube 12 into which the sample or reagent will be dispensed is positioned below the opening 331. When the dispensing unit 60 is positioned above the centrifugation unit 30, the lid 34 moves to the state shown in Figure 8, opening the opening 332. When the sample or reagent is dispensed into the centrifuge tube 12 by the dispensing unit 60, the lid 34 returns to the state shown in Figure 6, closing the opening 332. While this explanation describes the dispensing of a sample or reagent, the operation is similar when aspirating and removing liquid (e.g., supernatant) from the centrifuge tube 12.

[Sample preparation device operation]
Referring to Figure 9, the operation of the sample preparation device 100 will be described. Below, the movement of racks 10a to 10c by the rack transport unit 20 will be described, with further reference to Figures 10 to 13.

As shown in Figure 10, each rack 10a, 10b, and 10c can hold multiple containers (for example, six). Racks 10a, 10b, and 10c are transported in the X1 and X2 directions by the rack transport unit 20. In this embodiment, the rack transport unit 20 moves the racks integrally in the X1 and X2 directions; however, the rack transport unit 20 may also move the racks independently. The rack transport unit 20 can transport racks 10a, 10b, and 10c in the X1 and X2 directions at distances corresponding to the spacing between the containers held in the racks. Figures 10 to 13 show grids corresponding to the spacing between containers to clearly illustrate the position of each container.

<Specimen dispensing process>
Prior to sample dispensing, as shown in Figure 10(A), the user sets the containers in the racks 10a to 10c, which are in their initial positions. The initial positions of racks 10a to 10c refer to the state where each rack is furthest to the right (towards the X2 direction). The user sets an empty processing container 11 in rack 10a. The user also sets an empty centrifuge tube (reaction vessel) 12 in rack 10b. The user also sets a sample container 13 containing a blood sample in rack 10c.

In step S201 of Figure 9, the centrifuge tubes 12, which serve as reaction vessels, are transported from the rack 10b to the centrifuge section 30. As shown in Figure 10(B), the rack is moved in the X1 direction so that the leftmost centrifuge tube 12 is located at position P1. Position P1 is the 12th position from the rightmost position. At position P1, the centrifuge tube 12 is removed by the transfer unit 40 and transported to the centrifuge section 30. As shown in Figure 10(C), the rack is moved in the X1 direction so that the next centrifuge tube 12 is located at position P1. Then, the centrifuge tubes 12 are removed by the transfer unit 40 and transported sequentially to the centrifuge section 30. This process is repeated until the last centrifuge tube 12 is moved to position P1 and transported to the centrifuge section 30 by the transfer unit 40. The control unit 90 stores the relationship between each holder portion 32 of the rotor 31 and the holding position of the centrifuge tubes 12 set in each holder portion 32 on the rack 10b.

In step S202, the blood sample in the sample container 13 is agitated. As shown in Figure 11(A), the rack is moved in the X2 direction by the rack transport unit 20 so that the leftmost sample container 13 is positioned at position P2. Position P2 is the 8th position from the rightmost position. At position P2, the sample container 13 from rack 10c is removed by the agitation unit 51 and inverted for agitation.

In step S203, a blood sample is aspirated from the sample container 13 and discharged into the processing container 11 on the rack 10a, thereby dispensing the blood sample. As shown in Figure 11(B), the rack is moved in the X1 direction so that the sample container 13, which was agitated in step S202, is located at position P1. At position P1, the dispensing unit 50 aspirates a portion of the blood sample from the sample container 13 and dispenses the aspirated blood sample into the processing container 11 held on the rack 10a. As shown in Figure 11(C), the rack is moved in the X2 direction so that the next sample container 13 is located at position P2. At position P2, the sample container 13 is agitated by the agitation unit 51. This agitation of the sample container 13 at position P2 and the subsequent dispensing of the blood sample at position P1 are repeated until all sample containers 13 have been agitated. When a sample is dispensed from the sample container 13, the sample from the sample container 13 held at one holding position on rack 10c is dispensed into the processing container 11 held at the corresponding holding position on rack 10a. The corresponding holding position refers to the nth holding position from the end (right or left end) of one rack and the nth holding position from the same end of the other rack. For example, the sample from the sample container 13 held at the leftmost holding position on rack 10c is dispensed into the processing container 11 held at the corresponding holding position on rack 10a, i.e., the leftmost holding position. Other samples are dispensed similarly. Figure 11(D) shows the state after mixing and dispensing have been completed for all sample containers 13.

<BF separation process>
In step S204, antibodies are dispensed into the processing container 11 from which the blood sample was discharged. As shown in Figure 12(A), the rack is moved in the X2 direction so that the leftmost processing container 11 is at position P3. At position P3, the dispensing unit 60 dispenses biotinylated anti-erythrocyte antibodies into the processing container 11. As shown in Figure 12(B), the rack is moved in the X1 direction so that the next processing container 11 is at position P3. Then, the process of dispensing anti-erythrocyte antibodies into the processing container 11 by the dispensing unit 60 at position P3 is repeated.

Once dispensing into all processing containers 11 is complete, in step S205, the blood samples in the processing containers 11 are agitated. The rack transport unit 20 repeatedly moves the rack back and forth in the X1 and X2 directions, agitating the blood samples in the processing containers 11. The rack 10a holding the processing containers 11 is then left to stand for a predetermined time (e.g., 20 minutes).

In step S206, the buffer solution is dispensed into the processing container 11. The rack transport unit 20 moves the rack 10a, and at position P3, the buffer solution is dispensed into each processing container 11 by the dispensing unit 60. The rack transport unit 20 moves the rack 10a at high speed, agitating the blood sample in the processing container 11. Afterward, it is allowed to stand. For example, BSA solution and phosphate-buffered saline (PBS) can be dispensed as buffer solutions. The blood sample with the dispensed buffer solution is then agitated.

In step S207, magnetic particles are dispensed into the processing container 11. For example, streptavidin-bound magnetic particles are dispensed as the magnetic particles. As shown in Figure 12(C), the rack is moved in the X1 direction so that the leftmost processing container 11 is located at position P3. At position P3, streptavidin-bound magnetic particles as a solid phase are dispensed into the processing container 11 by the dispensing unit 60. As shown in Figure 12(D), the rack is moved in the X1 direction so that the next processing container 11 is located at position P3. Then, the process of dispensing the solid phase containing magnetic particles into the processing container 11 by the dispensing unit 60 at position P3 is repeated.

In step S208, the blood sample in the processing container 11 is agitated to carry out the reaction. This takes, for example, 5 minutes. The rack is moved at high speed by the rack transport unit 20, agitating the blood sample in the processing container 11. Afterward, it is left to stand. This forms a complex containing red blood cells and a solid phase within the processing container 11.

In step S209, magnetization is performed. As shown in Figure 12(E), the rack is moved in the X2 direction so that each processing container 11 is positioned at position P4. Position P4 corresponds to the sixth cell from the rightmost cell. A magnet 23 is provided adjacent to position P4. The magnet 23 magnetizes the composite containing red blood cells and solid phase on the inner surface of the processing container 11. The required time is, for example, 10 minutes.

In step S210, the supernatant (e.g., 700 μL) of the blood sample in the processing container 11 where magnetic collection is being performed is aspirated and dispensed into the centrifuge tubes 12 of the centrifuge unit 30. As shown in Figure 13(A), at position P4, the supernatant is aspirated from each processing container 11 by the dispensing unit 60 and dispensed into each centrifuge tube 12 that has been transferred to the centrifuge unit 30. When the supernatant (sample) is dispensed from the processing container 11, the supernatant (sample) from the processing container 11 held in one of the holding positions of the rack 10a is dispensed into the centrifuge tube 12 that was held in the corresponding holding position of the rack 10b. The corresponding holding position is as described above. For example, the supernatant (sample) from the processing container 11 held in the leftmost holding position of the rack 10a is dispensed into the processing container 11 that was held in the corresponding holding position of the rack 10a, i.e., the leftmost holding position, before being transferred to the centrifuge unit 30 (i.e., at the time shown in Figure 10(A)). As described above, the control unit 90 stores a correspondence between each holder portion 32 of the rotor 31 and the holding position of the centrifuge tubes 12 set in each holder portion 32 on the rack 10b. Based on the correspondence stored in the control unit 90, the dispensing unit 60 dispenses the supernatant (sample) from the processing container 11, held in one of the holding positions on the rack 10a, into the corresponding centrifuge tube 12 held in the corresponding holder portion 32 (i.e., the centrifuge tube 12 held in the corresponding holding position on the rack 10b). Other samples are dispensed in the same manner.

In step S212, the sample in the centrifuge tube 12 is centrifuged. The centrifuge unit 30 rotates the rotor 31 at high speed, causing the leukocytes to settle at the bottom of the centrifuge tube 12.

In step S213, the supernatant in the centrifuge tube 12 is removed. The dispensing unit 60 aspirates and removes the supernatant (e.g., 600 μL) from the centrifuge tube 12, from which the leukocytes have settled by centrifugation.

In step S214, the sample in the centrifuge tube 12 is stirred. In steps S212 and S213, leukocytes have settled at the bottom of the centrifuge tube 12. To disperse these settled leukocytes, the centrifuge tube 12 is stirred. The centrifuge unit 30 stirs the sample in the centrifuge tube 12 by rotating the rotor 31 while repeatedly accelerating and decelerating in one direction. In this embodiment, the stirring by the centrifuge unit 30 is described as repeated unidirectional acceleration and deceleration, but the rotation method for stirring may be intermittent rotation or rotation in both forward and reverse directions.

<First staining treatment>
In step S215, the antibody reagent is dispensed into the centrifuge tube 12. The dispensing unit 60 dispenses a cocktail reagent containing CD25-labeled antibody, CD4-labeled antibody, and CD62-labeled antibody as the antibody reagent into the centrifuge tube 12 held in the centrifuge unit 30.

In step S216, the centrifugal separator 30 rotates the rotor 31 in one direction while repeatedly accelerating and decelerating, thereby stirring the sample in the centrifuge tube 12 and allowing the reaction of the sample to proceed. The predetermined time is, for example, 30 minutes.

In step S217, the washing solution for the pre-fixation sample is dispensed into the centrifuge tube 12. The dispensing unit 60 dispenses PBS as the washing solution into the centrifuge tube 12.

In step S218, the centrifugal separator 30 stirs the sample in the centrifuge tube 12 by rotating the rotor 31 while repeatedly accelerating and decelerating in one direction.

In step S219, the centrifuge unit 30 centrifuges the sample in the centrifuge tube 12 by rotating the rotor 31 at high speed in one direction. This causes the leukocytes that have reacted with the antibody reagent to settle.

In step S220, the dispensing unit 60 aspirates and removes the supernatant from the centrifuge tube 12. As a result, the surface antigens CD25, CD4, and CD62 are stained with their respective labeling substances.

<Cell fixation and permeabilization>
In step S221, the dispensing unit 60 dispenses the fixative/permeabilizer into the centrifuge tube 12.

In step S222, the centrifugal separator 30 rotates the rotor 31 in one direction while repeatedly accelerating and decelerating, thereby stirring the sample in the centrifuge tube 12 and allowing the reaction to proceed. The predetermined time is, for example, 30 minutes.

In step S223, the dispensing unit 60 dispenses the washing solution for the sample to be fixed into the centrifuge tube 12.

In step S224, the centrifugal separator 30 stirs the sample in the centrifuge tube 12 by rotating the rotor 31 while repeatedly accelerating and decelerating in one direction.

In step S224, the centrifugal separator 30 centrifuges the sample in the centrifuge tube 12 by rotating the rotor 31 at high speed.

In step S226, the dispensing unit 60 aspirates and removes the supernatant from the centrifuge tube 12.

In steps S227 to S230, the washing solution is dispensed, stirred, centrifuged, and the supernatant is removed. In other words, the sample washing process is repeated. The sample washing process may be performed once, twice, three times or more. Through this process, the cells in the centrifuge tube 12 are immobilized and permeabilized.

<Second staining treatment>
In step S231, the dispensing unit 60 dispenses the antibody reagent into the centrifuge tube 12. For example, the antibody reagent dispensed may include a reagent containing Foxp3-labeled antibody.

In step S232, the centrifugal separator 30 rotates the rotor 31 in one direction while repeatedly accelerating and decelerating, thereby stirring the sample in the centrifuge tube 12 and carrying out the reaction. The predetermined time is, for example, 30 minutes.

In step S233, the dispensing unit 60 dispenses the washing solution for the fixed sample into the centrifuge tube 12. In steps S234 to S236, stirring, centrifugation, and removal of the supernatant are performed in the same manner as described above. In steps S237 to S240, the sample washing process, including dispensing the washing solution, stirring, centrifugation, and removal of the supernatant, is repeated. The sample washing process may be performed once, twice, three or more times. As a result, the FOXP3 in the centrifuge tube 12 is stained with the corresponding labeling substance.

<Container return>
In step S241, the dispensing unit 60 dispenses buffer solution into the centrifuge tube 12. Dispensing adjusts the sample in the centrifuge tube 12 to a predetermined volume and pH suitable for supply to the measuring device. For example, BSA solution and PBS are dispensed as buffer solutions.

In step S242, the centrifugal separator 30 rotates the rotor 31 in the same manner as described above to perform stirring.

In step S243, the transfer unit 40 removes the centrifuge tubes 12 held in the centrifugal separation unit 30 from the rotor 31 and sets them in the rack 10b held in the rack transfer unit 20. At this time, each centrifuge tube 12 is returned to its original position in the rack 10b. As described above, the control unit 90 stores the correspondence between each holder unit 32 of the rotor 31 and the holding position of the centrifuge tubes 12 set in each holder unit 32 in the rack 10b. Based on the correspondence stored in the control unit 90, the transfer unit 40 transfers the centrifuge tubes 12 held in each holder unit 32 so as to return them to their original holding positions in the rack 10b. For example, the centrifuge tube 12 that was held in the leftmost holding position in the initial position of Figure 10(A) is set to its original holding position (the leftmost holding position) when it is returned to the rack 10b as shown in Figure 13(B). The other centrifuge tubes 12 are similarly returned to their original holding positions in the rack 10b. Once all centrifuge tubes 12 have been transferred to the rack 10b, the rack transport unit 20 moves the rack in the X2 direction, as shown in Figure 13(D), returning it to its initial position. This allows the user to remove the centrifuge tubes 12. Thus, high safety is ensured because the user does not need to access the centrifuge unit 30, not only when setting the centrifuge tubes 12 into the centrifuge unit 30, but also when removing the centrifuge tubes 12. Furthermore, because the centrifuge tubes 12 containing the prepared samples are returned to their original holding positions on the rack 10b, the correspondence between the holding positions of the sample containers 13 and the centrifuge tubes 12 in the initial position is maintained, allowing the user to remove the centrifuge tubes 12. Therefore, it is easy for the user to understand which sample container 13 corresponds to which centrifuge tube 12, reducing the risk of sample mix-ups.

With the above steps, sample preparation using the sample preparation device 100 is completed.

(Operation process of the centrifugal separation section of the sample preparation device)
Next, referring to Figure 14, the operation process of the centrifugation unit 30 of the sample preparation apparatus 100 will be described.

The centrifugal separation unit 30 positions the rotor 31 at a desired rotational position by adjusting the rotational distance from the origin point.

In step S301, the rotor 31 of the centrifugal separator 30 is set to its origin. Then, the processes in step S410 (steps S302 to S305) are performed.

In step S410, first, in step S302, the θ-axis of the rotor 31 is moved to the set position of the centrifuge tube 12, which serves as the reaction vessel. Specifically, the rotation angle of the rotor 31 is adjusted to the position where the centrifuge tube 12 will be transported. In step S303, the Y-axis of the transport unit 40 is moved to the catch position. Then, the transport unit 40 catches the centrifuge tube 12 and transports it to the rotor 31.

Subsequently, in step S304, the Y-axis of the transfer unit 40 is moved to the origin position. In step S305, the θ-axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S302 to S305 (step S410) is repeated.

In step S306, the θ-axis of the rotor 31 is moved to the pipette access position where sample dispensing, reagent dispensing, or supernatant aspiration takes place. In step S307, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the sample is dispensed into the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

Subsequently, in step S308, the XY axes of the dispensing unit 60 are moved to the origin position. In step S309, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S306 to S309 is repeated.

Subsequently, the process in step S420 (steps S310 to S324) is repeated twice.

In step S420, first, centrifugation is performed in step S310, followed by the setting of the rotor 31 to its origin. In step S311, the θ-axis of the rotor 31 is moved to the pipette access position. In step S312, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the supernatant is aspirated and removed from the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S313, the XY axes of the dispensing unit 60 are moved to the origin position. In step S314, the θ axis of the rotor 31 is moved to the origin position. In step S315, the θ axis of the rotor 31 is driven to perform a strong stirring action. After that, the rotor 31 is set to its origin position.

In step S316, the θ-axis of the rotor 31 is moved to the pipette access position. In step S317, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the reagent is dispensed into the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S318, the XY axes of the dispensing unit 60 are moved to the origin position. In step S319, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S316 to S319 is repeated.

In step S320, the θ-axis of the rotor 31 is driven to perform a weak stirring motion. Afterward, the rotor 31 is set to its origin position.

In step S321, the θ-axis of the rotor 31 is moved to the pipette access position. In step S322, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the reagent is dispensed into the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S323, the XY axes of the dispensing unit 60 are moved to the origin position. In step S324, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S321 to S324 is repeated.

After repeating the process in step S420 (steps S310 to S324) twice, the process in step S430 (steps S325 to S334) is repeated twice.

In step S430, first, centrifugation is performed in step S325, followed by the setting of the rotor 31 to its origin. In step S326, the θ-axis of the rotor 31 is moved to the pipette access position. In step S327, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the supernatant is aspirated and removed from the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S328, the XY axes of the dispensing unit 60 are moved to the origin position. In step S329, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S326 to S329 is repeated.

In step S330, the θ-axis of the rotor 31 is driven to perform a strong stirring action. Afterward, the rotor 31 is set to its origin position.

In step S331, the θ-axis of the rotor 31 is moved to the pipette access position. In step S332, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the reagent is dispensed into the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S333, the XY axes of the dispensing unit 60 are moved to the origin position. In step S334, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S331 to S334 is repeated.

After repeating the process in step S430 (steps S325 to S334) twice, in step S335, the θ-axis of the rotor 31 is driven to perform a weak stirring operation. Following this, the rotor 31 is set to its origin position.

In step S336, the θ-axis of the rotor 31 is moved to the pipette access position. In step S337, the XY-axis of the dispensing unit 60 is moved to the pipette access position. Then, the reagent is dispensed into the centrifuge tube 12 of the rotor 31 by the dispensing unit 60.

In step S338, the XY axes of the dispensing unit 60 are moved to the origin position. In step S339, the θ axis of the rotor 31 is moved to the origin position. If there is another sample, the process from steps S336 to S339 is repeated.

Subsequently, the process in step S430 (steps S325 to S334) is performed twice. Then, step S410 (steps S302 to S305) is performed. In step S340, the rotor 31 of the centrifugal separator 30 is set to its origin, and the operation ends.

(Other configuration examples)
Referring to Figures 15 to 17, an example of the operation of the sample preparation process using the sample preparation device 100 with other configurations will be described.

As shown in Figure 15, the sample preparation apparatus 100 according to another configuration example includes a rack transport unit 20 and a centrifugal separation unit 30.

Furthermore, the sample preparation device 100 includes a container transport mechanism 22 comprising a sample table 15a for rotating and transporting the sample container 13, a removal processing table 15b for rotating and transporting the processing container 11, and a container transport table 15c for rotating and transporting the centrifuge tube 12.

The sample preparation device 100 includes a common drive unit 21c that rotates the sample table 15a, the removal processing table 15b, and the container transport table 15c around a rotation axis extending in the vertical direction.

Furthermore, the sample preparation device 100 includes a dispensing unit 44, a dispensing unit 45, a dispensing unit 46, and a dispensing unit 47. The dispensing unit 44 is rotatable around a rotation axis extending in the vertical direction. The dispensing unit 44 is also movable in the Z direction (vertical direction). The dispensing unit 44 aspirates a blood sample from the sample container 13 on the sample table 15a and dispenses the blood sample into the processing container 11 on the removal processing table 15b, thereby dispensing the blood sample.

The dispensing unit 45 is rotatable around a rotation axis extending in the vertical direction. It is also movable in the Z direction (vertical direction). The dispensing unit 45 aspirates reagents placed in the reagent placement unit 70c and dispenses them into the processing container 11 of the removal processing table 15b. The dispensing unit 46 is rotatable around a rotation axis extending in the vertical direction. It is also movable in the Z direction (vertical direction). The dispensing unit 46 aspirates reagents placed in the reagent placement unit 70d and dispenses them into the processing container 11 of the removal processing table 15b.

The dispensing unit 47 is rotatable around a rotation axis extending in the vertical direction. Furthermore, the dispensing unit 47 is movable in the Z direction (vertical direction). The dispensing unit 47 aspirates the supernatant after processing from the processing container 11 on the removal processing table 15b and discharges it into the centrifuge tube 12 on the container transport table 15c, dispensing the supernatant after processing of the blood sample.

Furthermore, the sample preparation apparatus 100 includes a container transfer unit 48. The container transfer unit 48 is rotatable around a rotation axis extending in the vertical direction. It is also movable in the Z direction (vertical direction). The container transfer unit 48 transfers the centrifuge tube 12 between the container transfer table 15c and the centrifuge unit 30.

Furthermore, the sample preparation device 100 includes a stirring unit 51 for agitating the blood sample. The stirring unit 51 agitates the blood sample within the sample container 13 by holding and vibrating the sample container 13.

Furthermore, the sample preparation device 100 includes a dispensing unit 63. The dispensing unit 63 is rotatable around a rotation axis extending in the vertical direction. It is also movable in the Z direction (vertical direction). The dispensing unit 63 aspirates reagents placed in the reagent placement unit 70e and dispenses them into the centrifuge tube 12 of the centrifuge unit 30. The dispensing unit 63 also aspirates and removes the supernatant from the blood sample in the centrifuge tube 12 of the centrifuge unit 30.

Furthermore, the sample preparation device 100 includes reagent placement sections 70c, 70d, and 70e.

The rack transport unit 20 includes a magnet 23 that forms a complex containing red blood cells and a solid phase, and separates the formed complex from the supernatant of the blood sample. The magnet 23 is, for example, a BF separation unit that performs BF separation.

The centrifugal separation unit 30 is, for example, a centrifugal separation unit capable of performing centrifugal separation. The centrifugal separation unit 30 includes a first centrifugal separation unit 30a and a second centrifugal separation unit 30b. The first centrifugal separation unit 30a and the second centrifugal separation unit 30b are driven independently of each other, and blood samples are processed in batches.

The sample table 15a is set with the sample container 13 at position P11. The sample container 13 set at position P11 is rotated counterclockwise in Figure 15 and moved to position P12. The sample container 13 at position P12 is agitated by the agitator 51. After agitation by the agitator 51, the sample container 13 is moved back to position P13, where the blood sample is aspirated by the dispensing unit 44. Subsequently, the sample containers 13 are sequentially moved as the next sample container 13 is processed, and finally moved to position P14. The sample container 13 moved to position P14 is removed. Note that setting the sample container 13 at position P11 and removing the sample container 13 from position P14 may be done by the user or by a separately provided sample transport device.

The removal processing table 15b is set with the processing container 11 at position P15. The processing container 11 set at position P11 is rotated counterclockwise in Figure 15 and moved to position P16. A blood sample is dispensed into the processing container 11 at position P16 by the dispensing unit 44. The processing container 11 from which the blood sample has been dispensed is moved to position P17, where a reagent is dispensed by the dispensing unit 45. Subsequently, the processing container 11 is moved to position P18, where a reagent is dispensed by the dispensing unit 46. After that, the processing container 11 is moved to position P19, where BF separation processing is performed by the magnet 23 of the rack transport unit 20. Then, the processing container 11 is moved to position P20, where the supernatant is aspirated by the dispensing unit 47. After that, the processing container 11 is moved to position P21 and removed. The setting of the processing container 11 at position P15 and the removal of the processing container 11 from position P21 may be performed by the user or by a separately provided container transport device.

The container transport table 15c is set with the centrifuge tube 12 at position P22. The centrifuge tube 12 set at position P22 is rotated counterclockwise in Figure 15 and moved to position P23. The supernatant of the blood sample is dispensed into the centrifuge tube 12 at position P23 by the dispensing unit 47. The centrifuge tube 12 from which the supernatant of the blood sample has been dispensed is moved to position P24. The centrifuge tube 12 at position P24 is transferred to the centrifuge unit 30 by the container transport unit 48. For example, the container transport unit 48 transfers the centrifuge tube 12 to the first centrifuge unit 30a if there is space available in the first centrifuge unit 30a. On the other hand, the container transport unit 48 transfers the centrifuge tube 12 to the second centrifuge unit 30b if there is no space available in the first centrifuge unit 30a. The centrifuge tubes 12 processed by the centrifugal separation unit 30 are transferred by the container transfer unit 48 to position P25 on the container transfer table 15c. Subsequently, the centrifuge tubes 12 are moved to position P26 and removed. Note that setting the centrifuge tubes 12 at position P22 and removing them from position P26 may be done by the user or by a separately provided container transfer device.

In the first centrifugation section 30a of the centrifugation unit 30, the centrifuge tube 12 is transferred to position P27 by the container transfer section 48. At position P28, the reagent is dispensed into the centrifuge tube 12 by the dispensing section 63. Also at position P28, the supernatant is aspirated from the centrifuge tube 12 by the dispensing section 63.

In the second centrifugation section 30b of the centrifugation unit 30, the centrifuge tube 12 is transferred to position P29 by the container transfer section 48. At position P30, the reagent is dispensed into the centrifuge tube 12 by the dispensing section 63. Also at position P30, the supernatant is aspirated from the centrifuge tube 12 by the dispensing section 63.

As shown in Figure 16(A), the sample container 13 on the sample table 15a is moved to position P12. At position P12, the sample container 13 is stirred by the stirring unit 51. After being stirred by the stirring unit 51, the sample container 13 is moved back to position P13, and the blood sample is aspirated by the dispensing unit 44. The blood sample aspirated at position P13 is then dispensed by the dispensing unit 44 into the processing container 11 at position P16 on the removal processing table 15b.

As shown in Figure 16(B), the processing container 11 on the removal processing table 15b from which the blood sample has been discharged is moved to position P17, where anti-erythrocyte antibodies are dispensed by the dispensing unit 60 via the dispensing unit 45. Subsequently, the processing container 11 is moved to position P18, where a solid phase containing buffer and magnetic material is dispensed by the dispensing unit 46. Then, the processing container 11 is moved to position P19, where magnetization is performed by the magnet 23 of the rack transport unit 20. Finally, the processing container 11 is moved to position P20, where the supernatant is aspirated by the dispensing unit 47. The supernatant aspirated at position P20 is then discharged and dispensed by the dispensing unit 47 into the centrifuge tube 12 at position P22 on the container transport table 15c.

As shown in Figure 17(A), the centrifuge tube 12 from which the supernatant of the blood sample has been discharged is moved to position P24. The centrifuge tube 12 at position P24 is then transferred to the centrifuge unit 30 by the container transfer unit 48. The centrifuge tube 12 at position P24 is then transferred to position P27 in the first centrifuge unit 30a or position P29 in the second centrifuge unit 30b.

In the centrifugation unit 30, reagent dispensing, centrifugation, and supernatant removal are repeatedly performed, and the cells of the blood sample are immunostained.

As shown in Figure 17(B), in the first centrifuge section 30a of the centrifuge section 30, the immunostained centrifuge tube 12 is moved to position P27. The centrifuge tube 12 at position P27 is then transferred to the container transfer table 15c by the container transfer section 48. Furthermore, in the second centrifuge section 30b of the centrifuge section 30, the immunostained centrifuge tube 12 is moved to position P29. The centrifuge tube 12 at position P29 is then transferred to the container transfer table 15c by the container transfer section 48.

(Variant)
It should be noted that the embodiments disclosed herein are illustrative and not restrictive in all respects. The scope of the present invention is indicated by the claims rather than by the description of the embodiments above, and further includes all modifications within the meaning and scope equivalent to the claims.

For example, in the above embodiment, a rack transport unit 20 that transports racks 10a to 10c along the X-axis was exemplified as a holding unit for holding the centrifuge tubes 12 set by the user. However, the form of the holding unit is not limited to this. For example, the holding unit and the centrifuge tubes 12 held in the holding unit do not need to move within the apparatus. For example, the transport unit 40 may move to the holding position where the user has set the centrifuge tubes 12, and then remove the centrifuge tubes 12 and transport them to the centrifugal separation unit 30.

In the above embodiment, the centrifuge tube 12 was returned to the rack transport unit 20 after centrifugation, but it may be transported to another location within the apparatus. For example, a sample storage area separate from the rack transport unit 20 may be provided within the apparatus, and the centrifuge tube 12 may be transported there after centrifugation. In other words, the location where the user sets the centrifuge tube 12 (i.e., the holding area) and the location where the user removes the centrifuge tube 12 after centrifugation may be separate.

10a: Rack, 10b: Rack, 10c: Rack, 11: Processing container, 12: Centrifuge tube, 13: Sample container, 20: Holding unit, 21a, 21c: Drive unit, 22: Container transport mechanism, 23: Magnet, 30: Centrifugal separation unit, 40: Transfer unit, 50: Dispensing unit, 51: Stirring unit, 60: Dispensing unit, 70a, 70b: Reagent placement unit, 90: Control unit, 100: Sample preparation device

Claims (15)

A sample preparation device for preparing a measurement sample from a specimen,
A holding part for holding the centrifuge tube,
A transfer unit for transferring the centrifuge tube held by the holding unit,
A dispensing unit for dispensing samples into the centrifuge tube before or after transfer by the transfer unit,
The system comprises a centrifuge unit that holds the centrifuge tube transferred by the transfer unit and rotates it to centrifuge the sample dispensed into the centrifuge tube,
The holding portion includes a first holding portion for holding a plurality of sample containers and a second holding portion for holding a plurality of centrifuge tubes.
The transfer unit returns the centrifuge tube containing the sample prepared from the sample in the sample container held in the first position of the first holding unit to the corresponding first position of the second holding unit after centrifugation, and returns the centrifuge tube containing the sample prepared from the sample container held in the second position of the first holding unit to the corresponding second position of the second holding unit after centrifugation.
Sample preparation device. The sample preparation apparatus according to claim 1, wherein the holding unit is located on the front side of the sample preparation apparatus, and the centrifugal separation unit is located at a predetermined distance from the holding unit. The sample preparation apparatus according to claim 2, wherein the centrifugal separation unit is located on the rear side of the sample preparation apparatus. The centrifugal separator comprises an opening for allowing access by the transfer unit and a movable lid for closing the opening.
The sample preparation apparatus according to any one of claims 1 to 3, wherein the lid opens the opening when the transfer unit accesses the centrifuge unit, and closes the opening after the transfer unit transfers the centrifuge tube to the centrifuge unit or removes the centrifuge tube from the centrifuge unit. The sample preparation apparatus according to claim 4, wherein the centrifugal separation unit stops rotating while the lid is open. The sample preparation apparatus according to any one of claims 1 to 5, wherein the dispensing unit dispenses the sample into the centrifuge tube transferred to the centrifuge unit. The holding part further holds a processing container different from the centrifuge tube,
The sample preparation apparatus according to any one of claims 1 to 6, wherein the dispensing unit includes a first dispensing unit for dispensing a sample into the processing container and a second dispensing unit for dispensing the sample processed in the processing container into the centrifuge tube. The sample preparation apparatus according to any one of claims 1 to 7 , wherein the holding part includes a first holding part for holding a plurality of sample containers and a second holding part for holding a plurality of centrifuge tubes. The sample preparation apparatus according to claim 8 , further comprising a drive unit that moves the first holding unit to position the sample container at an aspiration position for aspiration by the dispensing unit. The sample preparation apparatus according to claim 9 , wherein the drive unit moves the second holding unit to position the centrifuge tube in a gripping position for the transfer unit to grip the centrifuge tube. The holding part holds the centrifuge tube housed in the case,
The sample preparation apparatus according to any one of claims 1 to 10, wherein the transfer unit transfers the centrifuge tube housed in the case by gripping the case, and sets the centrifuge tube housed in the case in the centrifugal separation unit. The sample preparation apparatus according to claim 11 , wherein the case is made of a thermally conductive metal. The aforementioned case is cylindrical and has a flange provided at the top of the cylinder.
The sample preparation apparatus according to claim 11 or 12 , wherein the transfer unit grips the case by engaging with the flange. The sample preparation apparatus according to any one of claims 1 to 13, wherein the transfer unit comprises a pair of gripping parts for gripping the centrifuge tube, a support member for supporting the gripping parts, a first drive source for horizontally moving the support member at least between a position above the holding part and a position above the centrifugal separation unit, a second drive source fixed to the support member for vertically moving the gripping parts relative to the support member, and a third drive source fixed to the support member for opening and closing the gripping parts relative to the support member. The user transfers the centrifuge tube, which has been placed in the holding section, to the centrifugal separation section.
Dispensing the sample into the centrifuge tube that has been transferred to the centrifuge unit,
The sample contained in the centrifuge tube is centrifuged using the centrifuge unit,
The centrifuge tube after centrifugation is returned to the holding unit ,
The holding portion includes a first holding portion for holding a plurality of sample containers and a second holding portion for holding a plurality of centrifuge tubes.
A sample preparation method comprising the step of returning the centrifuge tube after centrifugation to the holding part, wherein the centrifuge tube containing the sample prepared from the sample in the sample container held at the first position of the first holding part is returned to the corresponding first position of the second holding part, and the centrifuge tube containing the sample prepared from the sample container held at the second position of the first holding part is returned to the corresponding second position of the second holding part .