JP7582482B2 - Specimen pretreatment device and specimen pool testing method - Google Patents

Description

The present invention relates to a specimen pretreatment device for preparing specimens to be tested or analyzed, and a specimen pool testing method using the specimen pretreatment device.

The spread of the novel coronavirus disease (COVID-19) is becoming serious worldwide, and containing its spread is an urgent issue. Even before the spread of COVID-19, various viral infections that cause severe symptoms, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), have frequently occurred, making preparations for new viral infections an important issue.

Known devices for detecting such viruses include those that use nucleic acid amplification methods such as polymerase chain reaction (PCR) or reverse transcription PCR (RT-PCR) using primers specific to the virus to determine the presence or absence and quantify the target gene sequence (DNA). For example, in the testing device described in Non-Patent Document 1, when an examiner places a sample and reagents in the device and issues a command to start measurement, a series of processes from pre-processing, such as adding reagents to the sample, to measurement are automatically carried out.

Particularly during periods of rapid spread of viral infections, it is desirable to be able to test for the presence or absence of infection quickly, easily, and at low cost in relatively small medical institutions and medical departments. One such testing method is the specimen pool testing method described in Non-Patent Document 2 (hereinafter sometimes simply referred to as the "pool testing method").

In pooled testing, samples (hereinafter sometimes referred to as "individual samples") taken from multiple subjects (generally five or less) are mixed to prepare a pooled sample, which is then tested using a testing device such as that described above. If the pooled sample is determined to be negative, all of the multiple individual samples from which the pooled sample was derived are determined to be negative. On the other hand, if the pooled sample is determined to be positive, the multiple individual samples from which the pooled sample was derived are tested individually, and the individual sample that is positive among the multiple individual samples is identified. This type of pooled testing method is effective in both improving the efficiency of testing and reducing costs, especially in situations where there are relatively few positive samples.

"AutoAmpTM Genetic Analysis Device", [Online], [Retrieved June 28, 2021], Shimadzu Corporation, Internet <URL: https://www.shimadzu.co.jp/cl/products/autoamp/index.html> "Guidelines for specimen pool testing for novel coronavirus disease (COVID-19)," [Online], [Retrieved June 28, 2021], Ministry of Health, Labor and Welfare, Internet <URL: https://www.mhlw.go.jp/content/000725922.pdf>

Although it is possible to improve the efficiency of the testing itself in the testing device with the pooled testing method, it requires additional pre-processing work that is not required for general testing of individual samples, namely, dispensing and mixing multiple individual samples to prepare a pooled sample. As the number of individual samples to be tested increases, the pre-processing work for preparing the pooled sample becomes considerably more complicated. To improve the efficiency of the entire testing process, it is necessary to make it possible to perform this complicated pooled sample preparation work in parallel with the testing work on the samples. In addition, since the preparation of pooled samples tends to increase the risk of infection, it is even more important to automate testing, including the preparation of pooled samples, from the perspective of both improving work efficiency and reducing risk.

Although the existing testing device described in Non-Patent Document 1 has been designed to automate testing to a large extent, such devices do not perform pre-processing suitable for pooled testing. For this reason, there is a strong demand for the practical application of a sample pre-processing device that can efficiently prepare pooled samples while reducing the risk of infection, in order to widely and easily implement pooled testing.

As described above, in the pooled testing method, all individual samples that were used to create a pooled sample are stored in a refrigerator or similar, and if the pooled sample tests positive, the stored individual samples must be tested promptly. For this reason, testing personnel must perform each of the following tasks: loading the individual samples into the pretreatment device to prepare the pooled sample, removing the prepared pooled sample from the pretreatment device and loading it into the testing device, removing and storing the individual samples from the pretreatment device, and removing the individual samples from the storage location and loading them into the testing device. At each of these work steps, operational errors are likely to occur, such as mismatching the pooled sample with the individual samples that were its source, or mixing up the samples. Such errors can lead to incorrect test results and overlooking infected individuals.

The present invention has been made to solve the above-mentioned problems, and one of its objectives is to provide a sample pretreatment device and a sample pool testing method that can prevent mistakes, particularly mistakes made by testers in the process of preparing pooled samples and testing them, such as mixing up samples or mismatching pooled samples with individual samples.

Another object of the present invention is to provide a sample pretreatment device and a sample pool testing method that can improve the efficiency of the series of tasks required to prepare pooled samples and reduce the risk of viral infection, etc., for testing personnel, etc.

One aspect of the specimen pretreatment device according to the present invention, which has been made to solve the above problems, is a specimen pretreatment device that prepares a pool specimen to be tested or analyzed by a testing device by mixing a plurality of individual specimens, comprising:
a plurality of individual sample racks, each of which holds a plurality of individual sample containers in which the individual samples to be combined into a pooled sample may be placed;
a pooled sample rack that holds a plurality of pooled sample containers in which pooled samples are prepared and that is loadable into the testing device;
a container in which the individual sample racks and the pool sample rack are detachably stored and which is detachably loaded in a predetermined position on a work table;
a dispensing unit configured to dispense individual samples from individual sample containers held in the individual sample rack onto a pool sample container held in the pool sample rack on the work table;
Equipped with.

In order to solve the above problems, one aspect of the specimen pool testing method according to the present invention is a specimen pool testing method using the above aspect of the specimen pretreatment device according to the present invention,
a preparation step of storing the individual sample rack containing a plurality of individual sample containers, each containing an individual sample, and the pooled sample rack containing empty pooled sample containers in the container and loading the container onto the work table, or storing the individual sample rack and the pooled sample rack in the container loaded onto the work table;
a dispensing step of dispensing, by the dispensing unit, each of the individual samples in the individual sample containers held in the individual sample rack into a pool sample container held in the pool sample rack on the work table to prepare a pool sample;
a transport step of removing the pooled sample rack, which holds the pooled sample containers containing the prepared pooled samples, from the container, transporting the pooled sample rack to the testing device, and loading the pooled sample rack into the testing device;
a testing step of performing a predetermined test on pooled samples in pooled sample containers held in the pooled sample rack loaded in the testing device;
has.

According to the above-described aspects of the sample pretreatment device and sample pool testing method of the present invention, the prepared pooled samples can be transported to the testing device together and subjected to testing without being separated. In addition, since the individual samples from which one pooled sample is prepared are collected in an individual sample rack, if the pooled sample tests positive, the testing personnel can quickly remove the individual samples corresponding to the pooled sample and subject them to individual testing.

In this way, in the above-mentioned aspect of the present invention, the correspondence between pooled samples and individual samples is clear, and both pooled samples and individual samples can be handled in rack units, making it difficult for samples to be mixed up during the procedure, and ensuring the accuracy of the test. In addition, the ease of attaching and detaching samples to the testing device and transporting samples is good, which contributes to improving work efficiency. Furthermore, since the preparation of pooled samples is performed substantially automatically, it is also effective in reducing the risk of virus infection for testing personnel.

1 is a schematic block diagram of an inspection system using an embodiment of a specimen pretreatment device according to the present invention; FIG. 2 is a schematic diagram showing the internal configuration of the specimen pretreatment device of the present embodiment. 3 is a schematic top view of a work table on which various members used in pretreatment are attached in the sample pretreatment device of the present embodiment. FIG. FIG. 4 is a schematic top view of the working table with the members attached thereto removed. 4 is a flowchart showing an example of a procedure of a sample pretreatment operation and an inspection operation using the sample pretreatment apparatus of the present embodiment. FIG. 13 shows an example of a sample management screen displayed during the sample pretreatment work. FIG. 13 is a schematic diagram for explaining a method of mounting an individual sample rack. FIG. 13 is a schematic diagram for explaining a method of attaching a handle to an individual sample rack.

Below, one embodiment of the sample pretreatment device and sample pool testing method related to the present invention is described with reference to the attached drawings.

[Testing system configuration]
1 is a schematic block diagram of a testing system using a sample pretreatment device according to one embodiment of the present invention. This testing system is capable of testing for the presence or absence of infection with the novel coronavirus that causes COVID-19 by a sample pool testing method.

As shown in Figure 1, this testing system includes a specimen pre-processing device 1, a PCR testing device 2, a control and processing device 3, an operation unit 4, and a display unit 5. The control and processing device 3 is a general-purpose personal computer, and dedicated control and processing software is installed on the computer. The operation unit 4 and the display unit 5 are input devices such as a keyboard and mouse and a display monitor attached to the personal computer.

The specimen pre-processing device 1 is a pre-processing device specialized for the pooled testing method, and is not used when testing individual specimens collected from subjects. On the other hand, the PCR testing device 2 is a device capable of testing both individual and pooled specimens. An apparatus that combines the PCR testing device 2 with the control/processing device 3 is, for example, an apparatus described in Non-Patent Document 1, and is an apparatus that can automatically perform processing to measure and analyze gene amplification by PCR (or RT-PCR) over time (real time).

As shown in the upper part of FIG. 1, the specimen pretreatment device 1 is a device that prepares one pooled specimen by mixing multiple individual specimens. Each individual specimen is derived from a biological sample such as saliva, nasopharyngeal swab, blood, or urine collected from a subject. In the case of a pooled test method, it is considered desirable to mix five or less individual specimens in order to ensure the same level of test accuracy as an individual test. In the standard method of use, this specimen pretreatment device 1 prepares one pooled specimen from four (or fewer) individual specimens. In addition, as an optional method of use, it is possible to change the method so that one pooled specimen is prepared from five individual specimens. However, the types of individual specimens and the number of individual specimens for preparing a pooled specimen are merely examples, and can be modified as appropriate as described below.

In the case of pool testing, the pooled samples prepared in the sample pre-processing device 1 are loaded into the PCR testing device 2 and subjected to testing. In the example described below, it is assumed that the testing personnel themselves transport the pooled samples from the sample pre-processing device 1 to the PCR testing device 2, but it is of course possible to automate this transport work and the work of loading the samples into the PCR testing device 2 using a robot or the like.

[Configuration of specimen pretreatment device]
Next, the sample pretreatment device 1 will be described in detail. Fig. 2 is a schematic diagram of the internal configuration of the sample pretreatment device 1. Fig. 3 is a schematic top view of a work table on which various members used for pretreatment in the sample pretreatment device 1 are attached. Fig. 4 is a schematic top view of the work table with the members attached thereto removed.

2 to 4 show three mutually orthogonal axes, the X-axis, the Y-axis, and the Z-axis, for ease of explanation. The installation surface of the sample pretreatment device 1 is parallel to the XY plane, and the Z-axis direction is the height (up and down) direction of the sample pretreatment device 1.

Figure 2 is a schematic diagram of the internal configuration of the specimen pretreatment device 1 as viewed from the side. As shown in Figure 2, the device 1 includes a dispensing unit 10, a first moving part 11, a working table 12, a second moving part 13, and a control part 14. The first moving part 11 includes an actuator (not shown) that moves the dispensing unit 10 in the horizontal direction (X-axis direction and Y-axis direction). The second moving part 13 includes an actuator (not shown) that moves the working table 12 in the horizontal direction (X-axis-Y axis direction). The actuators included in the first and second moving parts 11 and 13 respectively operate in response to instructions from the control part 14. It should be noted that one of the first and second moving parts 11 and 13 can be omitted.

The dispensing unit 10 includes a syringe 100 having a nozzle 101 extending in the Z-axis direction attached to its tip. Inside the nozzle 101, a plunger (not shown) that is movable along the Z-axis direction is provided. The syringe 100 is configured to aspirate an amount of liquid corresponding to the stroke length of the plunger in the Z-axis direction, and to eject an amount of liquid corresponding to the stroke length of the plunger in the Z-axis direction. The dispensing unit 10 includes an actuator (not shown) for moving the syringe 100 in the Z-axis direction, and an actuator (not shown) for moving the plunger in the nozzle 101 in the Z-axis direction. Both of these actuators operate according to instructions from the control unit 14.

As shown in Figures 3 and 4, the upper surface of the work table 12 extends parallel to the XY plane, and is provided with a container storage section 120, a dispensing tip holding section 121, and a tip disposal section 122.

The container 20 is removably loaded into the container storage section 120. The container 20 has an approximately rectangular parallelepiped outer shape and is equipped with a handle (not shown) that allows it to be hung and held. The dispensing tip holding section 121 is provided with a plurality of holding holes (20 in this example) that are circular in top view. As shown in FIG. 2, each of the holding holes is configured to hold a dispensing tip 26, which is a long tip, in an upright position. The dispensing tip 26 is attached to the nozzle 101 of the syringe 100 for use.

The number of dispensing tips 26 that can be held in the dispensing tip holder 121 is the same as the maximum number of individual sample containers 24 that can be stored in the container 20 (20 in this example). The tip disposal unit 122 is a removable box with an open top into which used dispensing tips 26 are disposed.

The container 20 includes individual sample rack storage sections 200, 201 in which five individual sample racks 21 (21A-21E) can be stored, and a pooled sample rack storage section 202 in which one pooled sample rack 22 can be stored. The five individual sample racks 21 (21A-21E) have substantially the same external shape, being roughly rectangular parallelepipeds. The individual sample rack storage sections 200 in which four of the individual sample racks 21A-21D are stored extend in the Y-axis direction and are arranged side by side in the X-axis direction. The individual sample rack storage section 201 in which the remaining individual sample rack 21E is stored extends in the X-axis direction and is arranged adjacent to the arrangement of the four individual sample racks 21A-21D in the Y-axis direction.

The individual sample rack 21E is used only when a pooled sample is to be prepared from five individual samples, that is, only in the optional usage of the sample pretreatment device 1 of this embodiment. Therefore, in the standard usage in this example, that is, when a pooled sample is to be prepared from four (or less) individual samples, the individual sample rack 21E is not used. In the standard usage, the individual sample racks 21A to 21D are stored only in the individual sample rack storage section 200 that extends in the Y-axis direction and is arranged in four rows in the X-axis direction. To indicate that it is not used in the standard usage, the individual sample rack 21E is shown by a dotted line in FIG. 2.

The pool sample rack storage section 202, like the individual sample rack storage section 201, extends in the X-axis direction and is positioned on the opposite side of the individual sample rack storage section 201 in the Y-axis direction, sandwiched between the arrangement of the four individual sample racks 21A to 21D.

Between the four rows of individual sample rack storage sections 200 and the pool sample rack storage section 202, a color labeling section 203 is provided, on which labels of the same color as those given to each of the individual sample racks 21A to 21D (in this case, the container holding sections are colored as described below) are affixed.

Each individual sample rack 21A-21D includes a container holder 210 capable of accommodating four individual sample containers 24, which are treated as one group for preparing one pool sample, arranged in a line with a predetermined distance between them. In each of the four individual sample racks 21A-21D, the container holder 210 is labeled with a different color for each individual sample rack 21A-21D. Specifically, in this example, the individual sample rack 21A is labeled with red, the individual sample rack 21B with blue, the individual sample rack 21C with green, and the individual sample rack 21D with purple. The color of this label corresponds to the color of the label on the color labeling section 203 on the container 20 described above. Of course, the colors are merely examples and are not limited to these.

Each of the four container holders 210 of the individual sample rack 21E that can be stored in the individual sample rack storage unit 201 is labeled in the same color as the container holders 210 in the four individual sample racks 21A to 21D that are aligned in the Y-axis direction in the state shown in Fig. 3. Therefore, in this example, the colors of the four container holders 210 in the individual sample rack 21E arranged as shown in Fig. 3 are red, blue, green, and purple, from left to right. That is, even when an individual sample rack E is used in addition to the individual sample racks 21A to 21D, the colors of the five container holders 210 aligned linearly in the Y-axis direction are the same, and the colors of the five rows of container holders 210 aligned in the X-axis direction are different from each other.

One pooled sample rack 22 can be stored in the pooled sample rack storage section 202. The pooled sample rack 22 is provided with a handle 23 that is inverted L-shaped when viewed from the side, as shown in Fig. 2. A testing personnel can grasp the handle 23 to securely hold the pooled sample rack 22 and insert/remove the pooled sample rack 22 into/from the pooled sample rack storage section 202 or carry the pooled sample rack 22. The handle 23 may be a member that can be attached/detached to the pooled sample rack 22, for example, having a shape and structure similar to that of the handle 30 shown in Fig. 8 described later.

Like the individual sample rack 21, the pool sample rack 22 is also provided with four container holders 220. The four container holders 220 are each labeled in the same color as the container holders 210 in the individual sample rack 21E. That is, in this example, the colors of the four container holders 220 in the pool sample rack 22 arranged as shown in FIG. 3 are red, blue, green, and purple, from left to right. In addition, numbers P1, P2, P3, and P4 are written on the top surface of the handle 23 from left to right corresponding to the four container holders 220, and the display colors of the numbers are the same as the colors given to each container holder 220.

As described above, the five individual sample racks 21A-21E basically have the same external shape, and the shapes of the individual sample rack storage units 200, 201 are also basically the same. However, the individual sample rack storage units 200, 201 in which the individual sample racks 21A-21E can be stored respectively are uniquely determined as follows, and the installation orientation is also uniquely determined.

Figure 7 is a schematic diagram for explaining a method of mounting the individual sample racks 21A to 21E. In Figures 3 and 4, the individual sample rack storage section 200A located at the leftmost position is provided with a position restricting piece 200a that protrudes inward from its inner surface. Meanwhile, the individual sample rack 21A is formed with a notch 21a at a position corresponding to the position restricting piece 200a (see Figure 7 (A)).

When the individual sample rack 21A is stored in the individual sample rack storage unit 200A in the appropriate orientation, the position restriction piece 200a fits exactly into the notch 21a, so that the individual sample rack 21A can be stored to the correct position (depth) (see FIG. 7(B)). In contrast, for example, if an attempt is made to store the individual sample rack 21A in the individual sample rack storage unit 200A with the orientation reversed, the bottom of the individual sample rack 21A abuts against the position restriction piece 200a, and the individual sample rack 21A is not completely stored in the individual sample rack storage unit 200A. This allows the testing personnel to easily recognize that they have attempted to store the individual sample rack 21A in the wrong orientation.

3 and 4, the individual sample rack storage section 200B, which is the second from the left in FIG. 3 and FIG. 4, also has a position restricting piece 200b protruding inward from its inner surface, but the position of the position restricting piece 200b is shifted in the Y-axis direction from the position restricting piece 200a. The individual sample rack 21B has a notch 21b formed at a position corresponding to the position restricting piece 200b (see FIG. 7(C)). Therefore, when the individual sample rack 21B is stored in the individual sample rack storage section 200B in the appropriate orientation, the position restricting piece 200b fits into the notch 21b, so that the individual sample rack 21B can be stored to the correct position (depth) (see FIG. 7(D)).

In contrast, for example, if an attempt is made to mistakenly store individual sample rack 21A in individual sample rack storage unit 200B, the position of position restriction piece 200b does not match the position of notch 21a, and the bottom of individual sample rack 21A abuts against position restriction piece 200b. As a result, individual sample rack 21A is not completely stored in individual sample rack storage unit 200B. This allows the testing personnel to easily recognize that they have attempted to store individual sample rack 21A that does not correspond to individual sample rack storage unit 200B. This is the same for all individual sample racks 21A-21E and individual sample rack storage units 200, 201.

That is, in this sample pretreatment device 1, the individual sample rack 21 and the individual sample rack storage units 200, 201 have a one-to-one physical (or structural) correspondence, and are configured so that the rack cannot be installed in an incorrect position. The same is true for the orientation of the individual sample rack 21, and it is configured so that the rack cannot be installed in an incorrect orientation. Furthermore, the same is true for the pooled sample rack 22, and the pooled sample rack 22 can only be installed in the pooled sample rack storage unit 202, and only in a fixed orientation.

As described above, the individual sample racks 21A-21D are each labeled with a different color, and the positions in which they should be stored are visually clearly indicated by the color labeling section 203. This allows the testing personnel to store the individual sample racks 21A-21D in the appropriate positions by referring to the colors. However, this is a measure to prevent operational errors that rely on the judgment of the testing personnel, and errors due to lack of attention on the part of the testing personnel may occur. In contrast, in this sample preprocessing device 1, the positions and orientations in which the individual sample racks 21A-21E and the pool sample rack 22 should be installed are physically and uniquely determined by the position control structure described above. This makes it possible to reliably prevent sample mix-ups caused by incorrect installation of the racks 21A-21E and 22.

[Pool inspection procedure]
Next, the procedure of the pool test in this testing system will be described. Fig. 5 is a flow chart showing the testing procedure in the pool test method including the sample pretreatment work in the sample pretreatment device 1. Note that, here, the example of preparing a pool sample from four individual samples, which is the standard usage method of this system, will be described.

First, the person in charge of testing checks whether or not the following items necessary for testing using the pool testing method are available (step S1).
Individual specimen containers 24 (up to 16 in number), each containing an individual specimen (a specimen taken from a subject).
- Empty pooled specimen containers 25 (maximum of four).
Dispensing tips 26 (maximum 16), which is the same number as the individual sample containers 24.
Pooled sample rack 22 (1 unit).
Individual sample racks 21A to 21D (maximum 4).
- Container 20 (1 piece).

The testing technician sets the dispensing tip 26 in the dispensing tip holder 121 of the sample pre-processing device 1 (step S2).

The testing personnel also places an empty pool sample container 25 in the pool sample rack 22 (step S3).

The testing personnel also places the individual sample containers 24 containing the individual samples in the individual sample racks 21A to 21D for the corresponding pool groups (step S4). Note that the order of steps S2 to S4 can be changed as appropriate.

The inspector starts the management software for the specimen preprocessing device 1 in the control/processing device 3 and performs a predetermined operation from the operation unit 4. This operation causes the display unit 5 to display a specimen management screen 50, as shown as an example in FIG. 6. The inspector inputs ID information for all individual specimens set in step S4 on this specimen management screen 50 (step S5). This input may be done manually by the inspector, or may be automatically input by reading barcodes affixed to the individual specimen containers 24 with a barcode reader.

In the example shown in FIG. 6, a sample management screen 50 displays a sample map 51 on the left side and a management table 52 on the right side.
The sample map 51 is a schematic diagram corresponding to a top view of the container 20 as shown in FIG. 3, showing objects corresponding to four individual sample racks and one pooled sample rack.

The management table 52 has four tabs corresponding to the four individual sample racks in the sample map 51, and the display color of each tab is the same as the symbol indicating the individual sample container in the sample map 51 that corresponds to it. Therefore, the testing personnel can easily visually grasp which individual sample rack the tab currently being worked on corresponds to.

Each tab in the management table 52 shows the pool sample number P1 to P4 corresponding to that tab, and the numbers 1 to 4 of the four individual sample containers to be set in the individual sample rack corresponding to that pool sample, and each is provided with a corresponding check box 521 and text boxes 522 and 524.

For example, when the testing personnel clicks on the "Auto-generate" button 523, ID information for the pooled sample corresponding to that tab is automatically generated and entered into the text box 534. The automatically generated ID information can be time information such as the current date, year, month, day, hour, minute, etc. This ID information can also be entered manually or automatically using a barcode, etc.

When ID information is being entered, the brightness of the display of the container (or rack) corresponding to that input on the sample map 51 increases. This allows the testing personnel to see at a glance on the sample map 51 which part of the input work is currently being performed. When the input of a line of ID information is completed, a check mark is automatically displayed in the corresponding check box 521, and the manner in which the display of the corresponding container (or rack) on the sample map 51 also changes (e.g., the brightness decreases).

When the testing technician clicks on an individual sample for which he or she wishes to enter ID information on the sample map 51, input becomes possible in the text box 522 corresponding to that individual sample in the management table 52. Input into the text box 522 can also be made by clicking on the text box 522 in the management table 52. In either case, while the ID information is being entered, the corresponding container is indicated on the sample map 51 by an arrow mark 511.

When input of ID information for an individual sample is complete, a check mark is automatically displayed in the corresponding check box 521, and the display of the corresponding container on the sample map 51 also changes. In this way, the testing personnel inputs ID information for all individual samples in the tabs corresponding to all individual sample racks. Whether input is complete can be confirmed by checking whether a check mark is displayed in the check box 521, and can also be easily confirmed by the display on the sample map 51.

As described above, the information entered on the sample management screen 50 is stored in a storage device provided in the control/processing device 3 and is used to manage individual samples and pooled samples, as well as the test results obtained for each sample, as described later.

Once the input of the ID information is complete, the testing technician sets the pooled sample rack 22 in a predetermined position in the container 20 (step S6). As described above, the pooled sample rack 22 can only be set in the container 20 in a specific orientation. The testing technician sets each of the four individual sample racks 21A-21D in a predetermined position in the container 20 (step S7).

As described above, the positions in the individual sample rack storage unit 200 where the individual sample racks 21A-21D should be set are uniquely determined by matching the colors given to the racks 21A-21D with the colors of the labels in the color labeling unit 203. This allows the testing personnel to associate the individual sample racks 21A-21D with the individual sample rack storage unit 200 without any hesitation.

Even if the testing personnel attempts to mount the individual sample racks 21A-21D in an incompatible individual sample rack storage unit 200, the above-mentioned position restriction structure prevents the racks from being mounted. Similarly, if the orientation of the individual sample racks 21A-21D to be mounted is reversed, the racks cannot be mounted due to the position restriction structure. As a result, the four individual sample racks 21A-21D can only be mounted in their corresponding individual sample rack storage units 200, and the correspondence is uniquely determined. This makes it possible to reliably prevent discrepancies between the ID information input by the testing personnel in step S5 and the individual samples actually stored in the container 20.

Then, the testing personnel sets the container 20 in the container storage unit 120 of the specimen pretreatment device 1 (step S8). As shown in FIG. 4, the container storage unit 120 is provided with a position restricting piece 120a that protrudes inward from its inner surface. Meanwhile, the container 20 is formed with a notch 20a at a position corresponding to the position restricting piece 120a. Therefore, like the individual specimen rack 21, the container 20 is also physically prevented from being installed in the wrong direction. This allows the testing personnel to properly install the container 20 in the container storage unit 120.

The testing personnel instructs the execution of pre-processing on the operation unit 4 (step S9). In response to this instruction, the control/processing device 3 sends an instruction to the control unit 14 of the sample pre-processing device 1. The control unit 14 controls the dispensing unit 10, the moving units 11 and 13, etc., to carry out the preparation process of the pooled samples.

Specifically, the specimen pretreatment device 1 performs the following processes.
The control unit 14 first mounts one dispensing tip 26 on the nozzle 101 of the syringe 100, and controls the dispensing unit 10, the moving units 11, and 13 to aspirate a predetermined amount of individual sample from the first (lowest in FIG. 3 ) individual sample container 24 held in the individual sample rack 21A and dispense it into the pool sample container 25 located at the same position in the Y-axis direction. Thereafter, the control unit 14 controls the dispensing unit 10, the moving units 11, and 13 to discard the used dispensing tip 26 in the tip disposal unit 122.

Next, the control unit 14 attaches a new dispensing tip 26 to the nozzle 101 of the syringe 100, and controls the dispensing unit 10 and the moving units 11 and 13 to aspirate a predetermined amount of individual sample from the second individual sample container 24 held in the individual sample rack 21A and dispense it into the previous pool sample container 25. After that, the used dispensing tip 26 is discarded in the tip disposal unit 122.

The same operation is performed for the third and fourth individual specimen containers 24 held in the individual specimen rack 21A, thereby dispensing four individual specimens into one pool specimen container 25. Thereafter, the control unit 14 controls the dispensing unit 10 and the moving units 11 and 13 to agitate the dispensed specimens by reciprocating the syringe 100 up and down a predetermined number of times, with the last used dispensing tip 26 attached to the nozzle 101.
In this manner, one pool sample is prepared by mixing the samples in the four individual sample containers 24 held in one individual sample rack 21A.

Next, in a similar manner, a pool sample is prepared by mixing the samples in the four individual sample containers 24 held in the individual sample rack 21B next to the individual sample rack 21A in the second pool sample container 25 from the left in the pool sample rack 22. The same is true for the individual sample racks 21C and 21D. Since one dispensing tip 26 is used to aspirate one individual sample, all of the prepared dispensing tips 26 are used by preparing four pool samples.

When all processing is completed in the specimen pre-processing device 1, the display unit 5 displays a message indicating that processing has been completed. Alternatively, the inspection personnel may be alerted by an alarm such as a buzzer. In response to this, the inspection personnel removes the container 20 from the specimen pre-processing device 1 (step S10).

Next, the testing personnel removes the pooled sample rack 22 from the removed container 20. The removed pooled sample rack 22 holds pooled sample containers 25 each containing a pooled sample. The testing personnel transports the pooled sample rack 22 to the PCR testing device 2 and sets it directly in the PCR testing device 2 (step S11). In this way, the four pooled sample containers 25 each containing a pooled sample prepared in the sample pretreatment device 1 can be set in the PCR testing device 2 without removing them from the pooled sample rack 22. This also makes it possible to avoid mixing up pooled samples in the process of setting multiple pooled samples in the PCR testing device 2.

Then, the PCR testing device 2 performs a predetermined analysis on the pooled samples in the four pooled sample containers 25 that have been set, and the control and processing device 3 analyzes the data obtained by the analysis to derive the test results for each pooled sample (step S12). The analysis performed by the PCR testing device 2 and the analysis process of the data obtained thereby are the same as those of existing devices described in, for example, Non-Patent Document 1, and therefore will not be described here.

After the pool sample rack 22 is removed from the container 20 in step S11, the testing personnel temporarily stores the container 20 with the individual sample racks 21A-21D stored therein in a storage facility such as a refrigerator. As a general rule, the individual sample racks 21A-21D should not be removed from the container 20 until all test results are available.

After completing the test in step S12, the tester checks the test results for the four pooled samples, and if all are negative, the tester issues a test result indicating that all 16 individual samples corresponding to the four pooled samples are negative. After this, all individual samples in container 20 that were temporarily stored in a refrigerator or the like can be discarded.

On the other hand, if the test result for one or more of the four pooled samples is positive, the testing personnel removes the container 20 from the refrigerator. Then, the testing personnel removes from the container 20 the individual sample racks 21A-21D corresponding to the pooled samples determined to be positive. Since the color of the container holder 220 of the pooled sample container 25 in which the positive pooled sample was stored in the pooled sample rack 22 is known, the testing personnel need only remove the individual sample racks 21A-21D that are given the same color. This reduces the mistake of removing individual sample racks 21A-21D corresponding to pooled samples that are not positive.

The testing technician attaches a handle 30 serving as an adapter to the individual sample rack 21 removed from the container 20. The testing technician grasps the handle 30 and transports the individual sample rack 21 to the PCR testing device 2, and sets the individual sample rack 21 with the handle 30 attached in the PCR testing device 2. Then, using the same procedure as for testing pooled samples, the technician tests each of the samples in the four individual sample containers 24 held in the individual sample rack 21. This determines which individual samples are positive. This makes it possible to identify the positive individual samples.

FIG. 8 is a schematic diagram for explaining a method of attaching the handle 30 to the individual sample rack 21. As shown in FIG.
8, the handle 30 has an integral structure including a bottom plate portion 30a that supports the bottom surface of the individual sample rack 21, a side plate portion 30b that covers one side surface of the individual sample rack 21 and extends to a position higher than the upper surfaces of the individual sample containers 24 held in the individual sample rack 21, and a grip portion 30c that extends horizontally from the upper edge of the side plate portion 30b. A hook portion 30d is provided on the side plate portion 30b.

8, when the individual sample rack 21 is lowered to a position where the bottom surface of the individual sample rack 21 abuts against the bottom plate portion 30a while one side of the individual sample rack 21 is abutted against the side plate portion 30b, the hook portion 30d hooks into a hook receiving portion (not shown) on the individual sample rack 21 side, and the handle 30 is attached to the individual sample rack 21. Note that, to prevent the handle 30 from coming off the individual sample rack 21, the individual sample rack 21 and the handle 30 may be pressed against each other by a biasing force of a leaf spring or the like.

The attachment/detachment structure between the individual sample rack 21 and the handle 30 is not limited to that shown in Fig. 8. For example, the individual sample rack 21 may be provided with a daruma groove, while the side plate portion 30b of the handle 30 may be provided with a protrusion that fits into the daruma groove, and a spring structure that is located on the back side of the protrusion and presses the protrusion or the side plate portion 30b itself against the individual sample rack 21.

In any of the above-mentioned structures, the individual sample rack 21 and the handle 30 are securely connected, which makes it possible to avoid accidents in which the individual sample rack 21 comes off the handle 30 during transport of the individual sample rack 21. Furthermore, by providing a spring structure on the handle 30 side, the testing personnel can physically recognize that the handle 30 is securely connected to the individual sample rack 21 when connecting the handle 30 to the individual sample rack 21. This makes it even more difficult for accidents to occur due to insufficient connection between the handle 30 and the individual sample rack 21.

As described above, in the testing system using the sample pretreatment device 1 of this embodiment, as a general rule, once an individual sample container 24 is set in the individual sample rack 21, the individual sample container 24 is not removed from the individual sample rack 21 until all testing processes are completed, including the individual testing after the pool testing. Therefore, the correspondence between the pool sample and the individual samples from which it was prepared is guaranteed, and even when multiple individual samples corresponding to a certain pool sample need to be tested individually, the risk of mixing up samples can be reduced.

In addition, the input ID information can be reliably matched to the individual sample containers in the individual sample rack 21, reducing the risk of mixing up samples. In addition, for prepared pooled samples, the pooled sample containers 25 containing the pooled samples can be transported and loaded from the sample preprocessing device 1 to the PCR testing device 2 without having to be removed from the pooled sample rack 22. This reduces the risk of mixing up pooled samples while handling multiple pooled samples.

Note that the above embodiment is merely one example of the present invention, and any appropriate modifications, additions, or amendments made within the spirit of the present invention will naturally be encompassed within the scope of the claims of this application.

For example, the structure that regulates the position and orientation of the individual sample rack 21 or the pool sample rack 22 when the individual sample rack 21 or the pool sample rack 22 is attached to the container 20 is not limited to the structure described above. Similarly, the structure that regulates the orientation of the container 20 when the container 20 is attached to the sample pretreatment device 1 is not limited to the structure described above.

Furthermore, it goes without saying that the shapes of each component, such as the container 20, the individual sample rack 21, the pool sample rack 22, etc., can be appropriately changed within the scope that enables the functions described above to be realized.

In addition, the configuration for dispensing and mixing each sample to prepare a pooled sample is not limited to that described above.

In addition, in the sample pretreatment device 1 in the above embodiment, typically, one pool sample is prepared from four or less individual samples that can be held in one individual sample rack, but the number of individual samples that can be held in one individual sample rack may be increased to n, which is five or more, and one pool sample may be prepared from the n individual samples held in that one individual sample rack. That is, one important element is that multiple individual samples used to prepare one pool sample can be stored together in one individual sample rack (in other words, there is no need to store them distributed across multiple individual sample racks).

In addition, in the above embodiment, a removable handle 30 is attached to the individual sample rack 21 and set in the PCR testing device 2, but as long as there is sufficient spacing between the multiple individual sample racks 21 (21A to 21E) on the work table 12 of the sample pre-processing device 1, the handle may be integrated with the rack, as in the pool sample rack 22.

[Various aspects]
It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

(Item 1) One aspect of the specimen pretreatment device according to the present invention is a specimen pretreatment device that prepares a pooled specimen to be tested or analyzed by a testing device by mixing a plurality of individual specimens,
a plurality of individual sample racks, each of which holds a plurality of individual sample containers in which the individual samples to be combined into a pooled sample may be placed;
a pooled sample rack that holds a plurality of pooled sample containers in which pooled samples are prepared and that is loadable into the testing device;
a container in which the individual sample racks and the pool sample rack are detachably stored and which is detachably loaded in a predetermined position on a work table;
a dispensing unit configured to dispense individual samples from individual sample containers held in the individual sample rack onto a pool sample container held in the pool sample rack on the work table;
Equipped with.

The specimen pretreatment device described in paragraph 1 is a device that prepares pooled specimens that are the subject of testing in a specimen pool testing method. In the specimen pretreatment device described in paragraph 1, a container can be loaded or removed from the specimen pretreatment device while the container contains multiple individual specimen racks and at least one pooled specimen rack. For example, after multiple pooled specimens have been prepared, the testing personnel removes the container from the specimen pretreatment device, takes out only the pooled specimen rack from the container, transports it to a testing device, and installs it in the testing device to perform testing. Meanwhile, the container containing the multiple individual specimen racks can be temporarily stored in a refrigerator as is.

This allows the prepared multiple pooled samples to be transported to the testing device together without being separated and subjected to testing. In addition, since the multiple individual samples from which the pooled sample was prepared are collected in an individual sample rack, when a pooled sample is positive, the testing personnel can quickly take out the multiple individual samples corresponding to the pooled sample and subject them to individual testing. In this way, the correspondence between the pooled sample and the individual samples is clear, and both the pooled sample and the individual samples can be handled in rack units, so that it is difficult for samples to be mixed up during the work, and the accuracy of the test can be ensured. In addition, the workability of attaching and detaching to the testing device and transporting from the sample pretreatment device to the testing device is also good, which contributes to the efficiency of the work. Furthermore, since the preparation of the pooled sample is substantially automatic, it is also effective in reducing the risk of virus infection for the testing personnel.

(Paragraph 2) In the sample pretreatment device described in paragraph 1, either or both of the multiple individual sample racks and the container may be provided with a position control unit that allows each of the multiple individual sample racks to be stored only in a specified position and in a specified orientation in the container.

If multiple individual sample racks have the same external shape and the storage locations for the individual sample racks in the container also have the same shape, there is a possibility that the individual sample racks will be mixed up when they are stored, which may result in mix-ups of individual sample containers. Similarly, there is a risk of mix-ups of individual sample containers if the orientation of the individual sample racks when stored in their storage locations in the container is not uniquely determined.

In contrast, according to the sample pre-processing device described in paragraph 2, when an individual sample rack is stored in a container, its storage position and orientation are uniquely determined, making it possible to more reliably prevent sample mix-ups due to carelessness on the part of the testing personnel, etc.

(Clause 3) In the sample pretreatment device described in paragraph 2, the position regulating unit may be a recess provided in either one of the plurality of individual sample racks or the container, and a protrusion provided in the other of the plurality of individual sample racks or the container, corresponding to the recess.

In the sample pre-processing device described in paragraph 3, if an inspector attempts to store an individual sample rack in a storage location of an individual sample rack in a container that does not correspond to that individual sample rack, for example, a convex portion on the individual sample rack will come into contact with a component of the storage location, and the individual sample rack will not be stored to the correct position. This allows the inspector to recognize that the individual sample rack does not correspond to the storage location. In this way, the sample pre-processing device described in paragraph 3 can reliably prevent the insertion of individual sample racks in the wrong location with a simple structure.

(4) In the sample pretreatment device described in any one of paragraphs 1 to 3, the multiple individual sample racks can be loaded into predetermined positions of the testing device either as is or by attaching a predetermined member.

According to the specimen pretreatment device described in paragraph 4, when it is necessary to individually test multiple individual specimens from which a pooled specimen is prepared, the multiple individual specimens can be subjected to testing in the individual specimen rack without removing the individual specimen containers containing the multiple individual specimens from the individual specimen rack. This improves the work efficiency when testing the individual specimens after the pooled test. It also avoids the risk of infection caused by removing the specimens.

(Clause 5) The specimen pretreatment device described in paragraph 4 further includes a gripping structure that can be attached to the individual specimen rack as the specified member, and the gripping structure can be loaded into the testing device in a state where it is attached to the individual specimen rack.

According to the specimen pretreatment device described in paragraph 5, the individual specimen racks are easy to hold, and accidents such as dropping the racks or specimen containers during transport can be prevented. This further reduces the workload of the testing personnel and the risk of infection.

(6) In the sample pretreatment device described in any one of paragraphs 1 to 5, the multiple individual sample racks may themselves be different colors from each other or may have labels of different colors attached to them, and in the container, each storage position for storing the multiple individual sample racks may be labeled with a label of the same color as the individual sample rack to be stored.

According to the sample pretreatment device described in paragraph 6, the individual sample racks can be associated with their storage positions in the container by color. This makes it possible to prevent the testing personnel from placing the individual sample racks in an inappropriate storage position when storing them in the container. As a result, unnecessary work is not performed, and work efficiency can be improved. Furthermore, even if the position restriction unit does not function properly (e.g., is physically damaged), the testing personnel can easily recognize the mistake and therefore avoid inappropriate testing.

(Section 7) In the sample pretreatment device described in Section 6, each holding position in the pool sample rack that holds the multiple pool sample containers may be labeled with a label of the same color as the color of the individual sample rack that holds the individual samples that are the source of the pool sample to be prepared in the pool sample container.

According to the sample pretreatment device described in paragraph 7, the individual sample rack (and the individual samples in the rack) can be associated with the pooled samples in the pooled sample rack by color. This makes it possible to prevent a person in charge from selecting the wrong individual sample rack when retrieving the individual sample rack corresponding to the desired pooled sample to perform an individual test.

(Clause 8) The specimen pretreatment device described in any one of clauses 1 to 7 may further include a position control section for allowing the container and/or the container loading section on the work table to be stored only in a specified orientation.

According to the sample pretreatment device described in paragraph 8, when a container is loaded into the container loading portion of the work table, its orientation is uniquely determined, thereby making it possible to avoid errors in loading the container due to carelessness on the part of the testing personnel, etc.

(Item 9) One aspect of the specimen pool testing method according to the present invention is a specimen pool testing method using the specimen pretreatment device described in items 1 to 8,
a preparation step of storing the individual sample rack containing a plurality of individual sample containers, each containing an individual sample, and the pooled sample rack containing empty pooled sample containers in the container and loading the container onto the work table, or storing the individual sample rack and the pooled sample rack in the container loaded onto the work table;
a dispensing step of dispensing, by the dispensing unit, each of the individual samples in the individual sample containers held in the individual sample rack into a pool sample container held in the pool sample rack on the work table to prepare a pool sample;
a transport step of removing the pooled sample rack, which holds the pooled sample containers containing the prepared pooled samples, from the container, transporting the pooled sample rack to the testing device, and loading the pooled sample rack into the testing device;
a testing step of performing a predetermined test on pooled samples in pooled sample containers held in the pooled sample rack loaded in the testing device;
has.

According to the specimen pool testing method described in paragraph 9, multiple pool specimens can be transported to a testing device together without being separated and subjected to testing. In addition, since the individual specimens from which the pool specimen is prepared are collected in an individual specimen rack, when a pool specimen is positive, the person in charge can quickly take out multiple individual specimens corresponding to the pool specimen and subject them to individual testing. In this way, the correspondence between the pool specimen and the individual specimens is clear, and both the pool specimen and the individual specimens can be handled in rack units, so that it is difficult for samples to be mixed up during the work, and the accuracy of the test can be ensured. In addition, the workability of attachment/detachment to the device and transportation is good, which contributes to the efficiency of the work. Furthermore, since the preparation of the pool specimen is performed substantially automatically, it is also effective in reducing the risk of virus infection, etc.

1...Sample pretreatment device 10...Dispensing unit 100...Syringe 101...Nozzle 11, 13...Moving section 12...Work table 120...Container storage section 120a...Position restriction piece 121...Dispensing tip holding section 122...Tip disposal section 14...Control section 2...PCR testing device 20...Container 200 (200A, 200B), 201...Individual sample rack storage section 200a, 200b...Position restriction piece 202...Pooled sample rack storage section 203...Color label section 21 (21A, 21B, 21C, 21D, 21E)...Individual sample rack 210, 220...Container holding section 22...Pooled sample rack 23, 30...Handle 24...Individual sample container 25...Pooled sample container 26...Dispensing tip 3...Control/processing device 4...Operation section 5...Display section

Claims (9)

A sample pretreatment device that mixes a plurality of individual samples to prepare a pooled sample to be tested or analyzed by a testing device, comprising:
a plurality of individual sample racks, each of which holds a plurality of individual sample containers in which the individual samples to be combined into a pooled sample may be placed;
a pooled sample rack that holds a plurality of pooled sample containers in which pooled samples are prepared and that is loadable into the testing device;
a container in which the individual sample racks and the pool sample rack are detachably stored and which is detachably loaded in a predetermined position on a work table;
a dispensing unit configured to dispense individual samples from individual sample containers held in the individual sample rack onto a pool sample container held in the pool sample rack on the work table;
A specimen pretreatment device comprising: The sample pretreatment device according to claim 1, wherein either or both of the plurality of individual sample racks and the container are provided with a position restriction unit that allows the plurality of individual sample racks to be stored only in a specified position and in a specified orientation in the container. 3. The sample pretreatment device according to claim 2, wherein the position regulating portion is a recess provided in either one of the plurality of individual sample racks or the container, and a protrusion provided in the other of the plurality of individual sample racks or the container, the protrusion corresponding to the recess.
The sample pretreatment device according to claim 1, wherein the individual sample rack can be loaded into a predetermined position of the testing device either as is or by attaching a predetermined part. The sample pretreatment device according to claim 4, further comprising a gripping structure that can be attached to the individual sample rack as the specified member, and the gripping structure can be loaded into the testing device in a state where it is attached to the individual sample rack. The sample pretreatment device according to claim 1, wherein the individual sample racks are themselves different colors from one another or have labels of different colors attached to them, and each storage position in the container for storing the individual sample racks is labeled with a label of the same color as the individual sample rack to be stored. The sample pretreatment device according to claim 6, wherein each holding position in the pool sample rack that holds the multiple pool sample containers is labeled with a color that is the same as the color of the individual sample rack that holds the individual samples that are the source of the pool sample to be prepared in the pool sample container. The specimen pretreatment device according to claim 1, wherein either or both of the container and the container loading section on the work table are provided with a position restriction section that allows the container to be stored only in a specified orientation. A sample pool testing method using the sample pretreatment device according to claim 1,
a preparation step of storing the individual sample rack containing a plurality of individual sample containers, each containing an individual sample, and the pooled sample rack containing empty pooled sample containers in the container and loading the container onto the work table, or storing the individual sample rack and the pooled sample rack in the container loaded onto the work table;
a dispensing step of dispensing, by the dispensing unit, each of the individual samples in the individual sample containers held in the individual sample rack into a pool sample container held in the pool sample rack on the work table to prepare a pool sample;
a transport step of removing the pooled sample rack, which holds the pooled sample containers containing the prepared pooled samples, from the container, transporting the pooled sample rack to the testing device, and loading the pooled sample rack into the testing device;
a testing step of performing a predetermined test on pooled samples in pooled sample containers held in the pooled sample rack loaded in the testing device;
A sample pool testing method comprising the steps of:

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