JP7540293B2 - Analysis equipment and reagent kits - Google Patents

Description

This disclosure relates to an analytical device for analyzing infectious diseases viruses or genes contained in a specimen to be analyzed (such as a biological sample such as blood, urine, nasopharyngeal swabs, or saliva), and a reagent kit that can be used with the analytical device.

Conventionally, there are devices for analyzing genes contained in a sample using the polymerase chain reaction (hereinafter also referred to as "PCR") (for example, Patent No. 4785862).

Patent No. 4785862

In genetic analysis using PCR, when a sample is placed in a sample container with a height of about 70 mm, it is assumed that the sample is located within a range of about 10 to 20 mm above the bottom of the sample container. When aspirating the sample in the sample container and dispensing it into a reaction container, it is assumed that a dispensing tip is attached to the tip of the nozzle of the dispensing device, the dispensing tip is inserted into the sample container, the sample in the sample container is aspirated from the tip of the dispensing tip, and the aspirated sample is dispensed into the reaction container. In this case, if a micro-dispensing tip (hereinafter also referred to as a "short tip") for collecting a very small amount of about a few μL is attached to the tip of the nozzle of the dispensing device, the short tip will penetrate deep into the sample container, increasing the possibility that droplets during dispensing will adhere not only to the short tip but also to the nozzle, increasing the possibility of infection or contamination.

As a countermeasure, it is envisaged to prepare a dispensing tip (hereafter also referred to as a "long tip") that is longer (deeper) than the short tip in addition to the shoot tip, and to provide the dispensing device with a nozzle that allows the long tip and short tip to be attached and detached.

However, the plunger that slides inside the nozzle of the dispensing device to aspirate and dispense liquid is thin because it is designed for small amounts, and there is concern that dispensing accuracy will decrease when using a long tip with the same stroke as a short tip.

This disclosure has been made to solve the above problems, and the purpose of this disclosure is to improve the accuracy of dispensing samples while making it difficult for samples to adhere to the nozzle of a dispensing device.

An analytical device according to an aspect of the present disclosure includes a tip used for dispensing liquid, a nozzle configured to detachably attach the tip, and a dispensing device that dispenses liquid into multiple containers via the tip attached to the nozzle, and a control device that controls the dispensing device. The tip includes a first tip and a second tip that is shallower than the first tip. The multiple containers include a specimen container containing a specimen, and a first reaction container and a second reaction container that are shallower than the specimen container. The control device controls the dispensing device to aspirate a second amount of specimen, which is greater than the first amount, from the specimen container with the first tip attached to the nozzle and dispense the specimen into the first reaction container, and to aspirate the first amount of specimen from the first reaction container with the second tip attached to the nozzle and dispense the specimen into the second reaction container.

According to the above-mentioned analysis device, the nozzle of the dispensing device is configured so that a first tip (long tip) and a second tip (short tip) that is shallower than the first tip can be detachably attached. Then, with the first tip (long tip) attached to the nozzle, a second amount of sample that is greater than a first amount (e.g., the amount required for analysis) is aspirated from the sample container and temporarily dispensed into the first reaction container. This allows the nozzle to be kept higher than when the sample is aspirated from the sample container with the second tip (short tip) attached to the nozzle, making it difficult for the sample to adhere to the nozzle.

Then, with the second tip attached to the nozzle, a first amount of sample (e.g., the amount required for analysis) is aspirated from the first reaction container and dispensed into the second reaction container. This improves the accuracy of dispensing the sample compared to when the first amount of sample is aspirated with the first tip (long tip) attached to the nozzle.

As a result, it is possible to improve the accuracy of dispensing the sample while preventing the sample from adhering to the nozzle of the dispensing device.

The analytical device disclosed herein can improve the accuracy of dispensing samples while making it difficult for samples to adhere to the nozzle of the dispensing device.

FIG. 1 is a diagram illustrating an example of a configuration of an analysis system. 1 is a view of the holding device with a container placed thereon, as viewed from the direction along the Z axis. 1 is a cross-sectional view of the holding device with a container placed thereon, as viewed from the direction along the Y axis. 13 is a diagram showing a state in which a long tip is attached to a nozzle of a syringe and the long tip is inserted into a sample container. FIG. 13 is a diagram showing a state in which a short tip is attached to a nozzle of a syringe and the short tip is inserted into a reagent container. FIG. 3A to 3C are diagrams illustrating steps of an analysis process performed by an analysis device. FIG. 13 is a diagram showing the process flow for dispensing 5 μL of a sample into a PCR container. FIG. 1 is a diagram (part 1) showing the process flow for adding 5 μL of a sample treatment solution to a PCR container. FIG. 1 is a diagram showing a process flow for adding each reagent to a PCR vessel. FIG. 1 is a diagram showing the amounts of each reagent pre-filled in four reagent containers provided as a reagent kit. FIG. 2 is a diagram showing a schematic appearance of the reagent kit. 13 is a diagram showing the internal state of the dispensing unit 12 when a dispensing tip is lowered toward a container with an open lid. FIG. 13 is a diagram showing the internal state of the dispensing unit 12 when a dispensing tip is lowered toward a container with a closed lid. FIG. 13 is a flowchart showing an example of a processing procedure executed by the control device when detecting a collision of a dispensing tip. FIG. 2 is a diagram (part 2) showing the process flow for dispensing 5 μL of sample into a PCR container. FIG. 3 is a diagram (part 3) showing the process flow for dispensing 5 μL of sample into a PCR container.

The following describes in detail the embodiments of the present disclosure with reference to the drawings. Note that the same or equivalent parts in the drawings are given the same reference numerals and their description will not be repeated.

Figure 1 is a schematic diagram showing an example of the configuration of an analysis system 1 according to the present embodiment. Analysis system 1 is an apparatus capable of fully automatically performing a process of measuring and analyzing gene amplification by PCR over time (real time). In the following, as shown in Figure 1, the direction along the vertical direction (the up and down direction in Figure 1) is also referred to as the "Z-axis direction," and the directions perpendicular to the vertical direction and perpendicular to each other are also referred to as the "X-axis direction" and "Y-axis direction," respectively.

The analysis system 1 includes an analysis device 2 and a terminal 3 capable of communicating with the analysis device 2. The terminal 3 is a general personal computer equipped with a display and operated by an operator.

The analysis device 2 includes an inspection device 10, a control device 20, a temperature adjustment device 30, and moving devices 4 and 5. The temperature adjustment device 30 includes a holding device (holder) 40 configured to hold a plurality of containers 50 and the like. The holding device 40 includes a temperature adjustment section 41 that has a temperature adjustment function (heating function and cooling function) using a Peltier element or the like, and a holding section 42 that does not have a temperature adjustment function.

The moving device 4 includes an actuator (not shown) that moves the inspection device 10 in the horizontal direction (X-axis and Y-axis directions). The moving device 5 includes an actuator (not shown) that moves the holding device 40 in the horizontal direction (X-axis and Y-axis directions). The actuators of the moving devices 4 and 5 operate according to commands from the control device 20. By moving at least one of the inspection device 10 and the holding device 40 in the horizontal direction using the moving devices 4 and 5, the relative horizontal distance between the inspection device 10 and the holding device 40 can be adjusted. Note that one of the moving devices 4 and 5 may be omitted.

The inspection device 10 includes an optical unit 11, a dispensing unit 12, an opening/closing unit 14, and an irradiation unit 16.

The dispensing unit 12 is equipped with a syringe 13 having a nozzle 13a extending in the Z-axis direction attached to its tip. A plunger (not shown) that can move along the Z-axis direction is provided inside the nozzle 13a. The syringe 13 is configured to aspirate an amount of liquid corresponding to the stroke amount of the plunger in the positive Z-axis direction, and to discharge an amount of liquid corresponding to the stroke amount of the plunger in the negative Z-axis direction. The dispensing unit 12 is equipped with an actuator (not shown) for moving the syringe 13 in the Z-axis direction, and an actuator (not shown) for stroking the plunger in the nozzle 13a in the Z-axis direction. These actuators operate according to commands from the control device 20.

The opening/closing unit 14 is equipped with an opening/closing mechanism having a protrusion for automatically opening and closing the lid of the container 50 by touching the lid of the container 50 held by the holding device 40. The opening/closing unit 14 operates according to commands from the control device 20.

In light of the risk that the specimen may adhere to the protrusions of the opening/closing unit 14 and become mixed (contaminated) with the next specimen when the opening/closing unit 14 opens and closes the lid of the container 50, the irradiation unit 16 prevents contamination by irradiating the area around the protrusions of the opening/closing unit 14 with UV light (ultraviolet light).

The optical unit 11 is a device that analyzes infectious disease viruses or genes contained in a specimen by detecting fluorescence emitted from the specimen when excitation light is irradiated onto the specimen in the container 50. The optical unit 11 detects fluorescence for each of the three wavelengths of red (R), green (G), and blue (B), and outputs the results to the control device 20. The optical unit 11 includes a light source (such as a light-emitting diode), a lens for irradiating the specimen with light from the light source and collecting the fluorescence from the specimen, and a photodiode for detecting the fluorescence emitted from the specimen and converting it into analyzable digital data. A known configuration can be used for the optical unit 11.

The control device 20 is configured to include a CPU (Central Processing Unit), memory, an input/output buffer, etc., all of which are not shown. When the control device 20 receives an analysis start command from the terminal 3, it analyzes the infectious disease virus or genes contained in the sample by controlling each part of the analysis device 2 (each unit in the testing device 10, the moving devices 4 and 5, and the temperature control section 41 of the temperature control device 30) according to a predetermined procedure. The control device 20 displays the analysis results by the analysis device 2 on the display of the terminal 3.

Figure 2 is a view of the holding device 40 with a container 50 placed thereon, viewed from the direction along the Z axis. The holding device 40 extends along the XY plane, and has an array surface on which a plurality of containers 50 are arranged two-dimensionally. The inspection device 10 and the holding device 40 are configured to be movable relative to each other two-dimensionally along the array surface of the holding device 40 by the moving devices 4 and 5.

The containers 50 arranged on the arrangement surface of the holding device 40 include PCR containers (reaction containers) 51 that contain the liquid to be subjected to the thermal cycle (samples with each reagent added), reagent containers 52 that contain each reagent, and sample containers 54 that contain individual samples.

The PCR containers 51 are arranged in four sets in the Y-axis direction, with four PCR containers 51a, 51b, 51c, and 51d arranged one-dimensionally along the X-axis direction as one set.

The reagent containers 52 are arranged in four sets in the Y-axis direction, with each set consisting of four reagent containers 52a, 52b, 52c, and 52d arranged one-dimensionally along the X-axis direction. Sample treatment liquid is pre-filled in the reagent container 52a. Reagent container 52b is pre-filled with reaction liquid. Reagent container 52c is pre-filled with primer/probe liquid (liquid containing primer and probe). Reagent container 52d is pre-filled with enzyme liquid. The four reagent containers 52a, 52b, 52c, and 52d are provided (commercially available) as a set in a reagent kit, with the amount of reagent required for the analysis of at least one sample sealed inside.

Four specimen containers 54 are arranged one-dimensionally along the Y-axis direction. In the analysis device 2 according to this embodiment, four specimen containers 54 arranged in the Y-axis direction are each filled with a different specimen, so that four specimens can be analyzed at once.

At the locations where each container 50 (PCR container 51, reagent container 52, specimen container 54) is placed in the holding device 40, steps (holes or recesses) are formed into which a portion of each container 50 can be inserted along the Z-axis direction. By inserting each container 50 into the corresponding step, the position of each container 50 in the X-axis and Y-axis directions is fixed.

A dispensing tip 53 for dispensing the sample and reagent is also disposed in the region between the reagent container 52 and the sample container 54 in the holding device 40. The dispensing tip 53 is attached to the nozzle 13a of the syringe 13 when in use.

In this embodiment, the dispensing tips 53 include a long tip 53a used for the sample container 54, and a short tip (micro tip) 53b used for the PCR container 51 and the reagent container 52. The depth of the short tip 53b is shallower than the depth of the long tip 53a. The opening diameter of the tip of the short tip 53b is smaller than the opening diameter of the tip of the long tip 53a. The dispensing tips 53 are arranged in four sets in the Y-axis direction, with one long tip 53a and two short tips 53b arranged one-dimensionally along the X-axis direction as one set.

The PCR container 51 to be subjected to the thermal cycle is placed in a temperature control section 41 having a temperature control function, and the other reagent containers 52, dispensing tips 53, and sample containers 54 are placed in a holding section 42 that does not have a temperature control function.

Furthermore, the holding device 40 is provided with a tip disposal section 43 for disposing of used dispensing tips 53.

Although not shown in FIG. 2, each container 50 is a resin molded product in which the lid and the container body are integrated, and the lid is configured to be able to be opened and closed.

Figure 3 is a cross-sectional view of the holding device 40 with the container 50 installed, viewed from the direction along the Y axis. As also shown in Figure 2, the holding device 40 has a sample container 54, a long tip 53a, two short tips 53b, reagent containers 52a, 52b, 52c, and 52d, and PCR containers 51a, 51b, 51c, and 51d arranged in this order along the X axis.

The PCR container 51 and the reagent container 52 are general-purpose containers of the same shape and size, and the heights (dimension in the Z-axis direction) Z1 of the PCR container 51 and the reagent container 52 are the same value (for example, about 20 mm). On the other hand, the specimen container 54 is a container that is larger in size than the PCR container 51 and the reagent container 52. Therefore, the height Z4 of the specimen container 54 is set to a value larger than the height Z1 of the PCR container 51 and the reagent container 52 (for example, about 70 mm).

When a specimen is contained in the specimen container 54, it is assumed that the specimen is located in a range of about 10 to 20 mm above the bottom of the specimen container 54, with the height Z1 of the specimen container 54 being about 70 mm. Therefore, with a short tip 53b of about 20 mm in height, the short tip 53b will penetrate deep into the specimen container 54, increasing the possibility that droplets generated during dispensing will adhere not only to the short tip 53b but also to the nozzle 13a, increasing the possibility of infection or contamination.

To address this issue, in this embodiment, a short tip 53b is used for the PCR container 51 and the reagent container 52. The height (dimension in the Z-axis direction) Z2 of the short tip 53b is set to a value greater than the height Z1 of the PCR container 51 and the reagent container 52. On the other hand, a long tip 53a is used for the specimen container 54. The height (dimension in the Z-axis direction) Z3 of the long tip 53a is set to a value greater than the height Z4 of the specimen container 54.

Furthermore, in this embodiment, the nozzle 13a of the syringe 13 is configured to be able to mount both the short tip 53b and the long tip 53a.

Figure 4 shows the state in which a long tip 53a is attached to the nozzle 13a of the syringe 13 and the long tip 53a is inserted into a sample container 54. Figure 5 shows the state in which a short tip 53b is attached to the nozzle 13a of the syringe 13 and the short tip 53b is inserted into a reagent container 52a.

As shown in FIG. 4, the nozzle 13a has a portion having a diameter D1 that is sized to fit into the opening diameter of the end of the long tip 53a. When attaching the long tip 53a to the nozzle 13a, the nozzle 13a is inserted into the long tip 53a until the opening of the long tip 53a is positioned in the portion of the nozzle 13a having the diameter D1, thereby fitting the nozzle 13a and the long tip 53a together.

Furthermore, as shown in FIG. 5, a portion having a diameter D2 (D2<D1) that is sized to fit into the opening diameter of the end of the short tip 53b is provided on the tip side of the portion having the diameter D1 in the nozzle 13a. When attaching the short tip 53b to the nozzle 13a, the nozzle 13a is inserted into the short tip 53b until the opening of the short tip 53b is positioned in the portion having the diameter D2 of the nozzle 13a, whereby the nozzle 13a and the short tip 53b are fitted together.

When removing the long tip 53a or short tip 53b fitted to the nozzle 13a from the nozzle 13a, the nozzle 13a is moved upward with the upper end of the long tip 53a or short tip 53b hooked onto the lower surface of the recess in the tip disposal section 43, and the long tip 53a or short tip 53b is removed from the nozzle 13a and discarded.

<Analysis processing>
When the operator sets each container 50 (PCR container 51, reagent container 52 and sample container 54) and dispensing tip 53 (long tip 53a and short tip 53b) in the holding device 40 and inputs an analysis start command to start the analysis into the terminal 3, the analysis process by the analysis device 2 is started.

Figure 6 is a diagram showing the steps of the analysis process performed by the analysis device 2. In the analysis process, steps S1 to S6 are performed in this order.

First, in step S1, a process (sample injection) is performed in which 5 μL of sample is dispensed into the PCR container 51b.

Figure 7 shows the process flow for dispensing 5 μL of sample into PCR container 51b in step S1. First, the control device 20 attaches the long tip 53a to the nozzle 13a of the syringe 13. Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to collect 25 μL of sample from the sample container 54 and dispense 25 μL of sample into the PCR container 51a, as shown by line L1 in Figure 7.

Next, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to discard the long tip 53a in the tip disposal section 43.

Next, the control device 20 attaches the first short tip 53b to the nozzle 13a of the syringe 13. Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to collect 5 μL of sample from the PCR container 51a and dispense 5 μL of sample into the PCR container 51b, as shown by line L2 in FIG. 7.

In step S1, 25 μL of the sample is collected with the long tip 53a and temporarily dispensed into the PCR vessel 51a, and then the short tip 53b is used to collect 5 μL of the sample from the PCR vessel 51a and dispense it into the PCR vessel 51b in order to accurately dispense 5 μL of the sample into the PCR vessel 51b. That is, the plunger provided inside the nozzle 13a of the syringe 13 is thin because it is basically made to correspond to the short tip 53b that dispenses a small amount, and with the same stroke amount, the dispensing accuracy decreases when using the long tip 53a, and accurate results may not be obtained. Therefore, in this embodiment, the sample is once collected with the long tip 53a and 25 μL, which is more than 5 μL, is dispensed into a PCR vessel 51a other than the PCR vessel 51b, and then the short tip 53b is used to collect 5 μL accurately from the PCR vessel 51a and dispense it into the PCR vessel 51b. This allows a small amount of sample of 5 μL to be accurately dispensed into the PCR vessel 51b.

In the next step S2, 5 μL of sample treatment liquid is added to the PCR container 51b.

Figure 8 shows the process flow for adding 5 μL of specimen treatment liquid to PCR container 51b in step S2. First, the control device 20 collects 5 μL of specimen treatment liquid from reagent container 52a and dispenses 5 μL of specimen treatment liquid into PCR container 51b, as shown by line L3 in Figure 8.

In this case, if only 5 μL of specimen processing liquid is placed in the reagent container 52a, air may be mixed in, resulting in "dry aspiration." In consideration of this, the reagent container 52a provided (commercially available) as a reagent kit contains a total of 8 μL of specimen processing liquid, which is the amount used of 5 μL plus an extra amount of 3 μL to prevent dry aspiration. This allows 5 μL of specimen processing liquid to be dispensed accurately into the PCR container 51b.

Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 so that the syringe 13 moves back and forth (up and down) to stir the inside of the PCR container 51b, as shown by line L4 in Figure 8.

Next, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to discard the first short tip 53b in the tip disposal section 43.

Returning to FIG. 6, the next step S3 will be described. In step S3, a process of heating and rapidly cooling the PCR container 51b is performed. Specifically, the control device 20 controls the temperature adjustment unit 41 to heat the PCR container 51b to maintain the sample temperature in the PCR container 51b at 90°C for 5 minutes, and then rapidly cool the PCR container 51b to return the sample temperature in the PCR container 51b to 20°C (room temperature).

In the next step S4, each reagent is added to the PCR container 51b.
9 is a diagram showing the flow of the process of adding each reagent to the PCR container 51b in step S2. The control device 20 first attaches the second short tip 53b to the nozzle 13a of the syringe 13. Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to collect 7.8 μL of reaction liquid from the reagent container 52b and dispense it into the reagent container 52d, which already contains 2.4 μL of enzyme liquid, as shown by the line L5 in FIG.

Then, as shown by line L6 in FIG. 9, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to collect 7.8 μL of primer/probe liquid from the reagent container 52c and dispense it into the reagent container 52d containing 7.8 μL of reaction liquid and 2.4 μL of enzyme liquid. Then, as shown by line L7 in FIG. 9, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to stir the inside of the reagent container 52d by reciprocating (up and down movement) the syringe 13. At this point, the amount of the reagent mixture in the reagent container 52d is 18 μL. The 18 μL of reagent mixture in the reagent container 52d is broken down into 7.8 μL of reaction liquid, 7.8 μL of primer/probe liquid, and 2.4 μL of enzyme liquid.

Next, as shown by line L8 in Figure 9, the control device 20 collects 15 µL from the 18 µL of reagent mixture contained in reagent container 52d and dispenses 15 µL of reagent mixture into PCR container 51b. The 15 µL of reagent mixture dispensed into PCR container 51b consists of 6.5 (= 7.8 x 15/18) µL of reaction solution, 6.5 (= 7.8 x 15/18) µL of primer/probe solution, and 2.0 (= 2.4 x 15/18) µL of enzyme solution.

Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 so that the syringe 13 moves back and forth (up and down) to stir the inside of the PCR container 51b, as shown by line L9 in Figure 9.

As described above, in step S4, 6.5 μL of reaction solution, 6.5 μL of primer/probe solution, and 2.0 μL of enzyme solution are added to PCR vessel 51b containing 5 μL of sample and 5 μL of sample treatment solution. In other words, the required amounts of reaction solution, primer/probe solution, and enzyme solution for 5 μL of sample and 5 μL of sample treatment solution are 6.5 μL, 6.5 μL, and 2.0 μL, respectively (15 μL in total).

When 15 μL of the reagent mixture is aspirated from the reagent container 52d using the short tip 53b, empty aspirate may occur if only 15 μL of the reagent mixture is placed in the reagent container 52d. Therefore, in this embodiment, a total of 18 μL of the reagent mixture, consisting of the required amount of 15 μL plus an extra amount of 3.0 μL, is dispensed into the reagent container 52d, and 15 μL is taken from the 18 μL of the reagent mixture in the reagent container 52d and dispensed into the PCR container 51b. This allows the 15 μL of the reagent mixture to be dispensed more accurately from the reagent container 52d to the PCR container 51b.

Furthermore, in this embodiment, 7.8 μL of reaction solution, 7.8 μL of primer/probe solution, and 2.4 μL of enzyme solution are used to obtain 18 μL of reagent mixture with the same mixing ratio as the total of 15 μL of reagent mixture containing 6.5 μL of reaction solution, 6.5 μL of primer/probe solution, and 2.0 μL of enzyme solution.

In this case, considering that the enzyme liquid has the highest manufacturing cost among the reaction liquid, primer/probe liquid, and enzyme liquid, in the present embodiment, measures have been taken to reduce the amount of enzyme liquid used. Specifically, 7.8 μL each of the reaction liquid and primer/probe liquid are aspirated from reagent containers 52b and 52c, and dispensed into reagent container 52d containing 2.4 μL of enzyme liquid.

In addition, reagent container 52b provided (commercially available) as a reagent kit is pre-filled with a total of 10.8 μL of reaction liquid, which is the amount used of 7.8 μL plus an extra amount of 3.0 μL to prevent empty aspiration, and reagent container 52c is pre-filled with a total of 10.8 μL of primer/probe liquid, which is the amount used of 7.8 μL plus an extra amount of 3.0 μL to prevent empty aspiration. This prevents empty aspiration when the reaction liquid and primer/probe liquid are aspirated from reagent containers 52b and 52c and dispensed into reagent container 52d. Furthermore, reagent container 52d provided (commercially available) as a reagent kit does not contain an extra amount of enzyme liquid, and only 2.4 μL of enzyme liquid is pre-filled. This makes it possible to reduce the amount of enzyme liquid used, which is the most expensive.

Figure 10 shows the amount of each reagent pre-filled in the four reagent containers 52a, 52b, 52c, and 52d provided as part of the reagent kit.

Reagent container 52a is pre-filled with 8.0 μL of specimen processing solution, which is the amount used of 5.0 μL plus an extra amount of 3.0 μL to prevent empty aspiration. Reagent container 52b is pre-filled with 10.8 μL of reaction solution, which is the amount used of 7.8 μL plus an extra amount of 3.0 μL to prevent empty aspiration. Reagent container 52c is pre-filled with 10.8 μL of primer/probe solution, which is the amount used of 7.8 μL plus an extra amount of 3.0 μL to prevent empty aspiration.

On the other hand, reagent container 52d does not contain any extra liquid to prevent empty collection, and only contains 2.4 μL of enzyme solution for use.

The required amounts of the sample treatment solution, reaction solution, primer/probe solution, and enzyme solution are 5.0 μL, 6.5 μL, 6.5 μL, and 2.0 μL, respectively. Therefore, each reagent is filled in excess of the required amount, but in this embodiment, it can be seen that the excess amount of the most expensive enzyme solution (= 0.4 μL) is kept lower than the excess amounts of the other reagents.

Figure 11 is a diagram showing a schematic view of the appearance of the reagent kit. As shown in Figure 11, this reagent kit includes four reagent containers 52a, 52b, 52c, and 52d arranged in a one-dimensional manner with adjacent containers connected to each other, and is provided in a state where the four reagent containers 52a, 52b, 52c, and 52d are packaged in packaging material 55. The lids of each of the four reagent containers 52a, 52b, 52c, and 52d are in a closed state. The packaging material 55 may be a paper box or a plastic bag.

As shown in FIG. 10, reagent container 52a is pre-filled with 8.0 μL of sample treatment liquid, reagent container 52b is pre-filled with 10.8 μL of reaction liquid, reagent container 52c is pre-filled with 10.8 μL of primer/probe liquid, and reagent container 52d is pre-filled with 2.4 μL of enzyme liquid.

By using such a reagent kit, the operator can efficiently start the analysis process. In other words, instead of setting each of the separated reagent containers 52a, 52b, 52c, and 52d in the holding device 40, the operator can complete the setting work of the reagent containers 52 by simply removing the one-dimensionally connected reagent containers 52a, 52b, 52c, and 52d from the packaging material 55 and setting them in the holding device 40.

Furthermore, as other consumables, a set of four PCR containers 51 and dispensing tips 53 (long tip 53a and short tip 53b) may be sold in combination.

In FIG. 11, four reagent containers 52a, 52b, 52c, and 52d (four PCR tubes) in which adjacent containers are connected to each other are provided as a reagent kit, but eight PCR tubes, each consisting of two sets of four reagent containers 52a, 52b, 52c, and 52d, may also be provided as a reagent kit.

Returning to FIG. 6, the next step S5 will be described. In step S5, a thermal cycle process is performed on the PCR container 51b. Specifically, the control device 20 controls the temperature adjustment unit 41 to maintain the liquid temperature in the PCR container 51b at 42°C for 10 minutes to cause a reverse transcription reaction, and then to maintain the liquid temperature in the PCR container 51b at 95°C for 1 minute to activate the enzyme.

Next, the control device 20 controls the temperature adjustment unit 41 to maintain the liquid temperature in the PCR container 51b at 95°C for 5 seconds, and then maintain the liquid temperature in the PCR container 51b at 60°C for 30 seconds to perform an amplification process to amplify the genes. This amplification process is performed for 45 cycles.

In the next step S6, three-wavelength fluorescence detection is performed. Specifically, the control device 20 controls the temperature adjustment unit 41 and the optical unit 11 so that after the amplification process, the temperature of the liquid in the PCR container 51b is set to 60°C and three-wavelength fluorescence detection is performed on the liquid in the PCR container 51b. The three-wavelength fluorescence detection is performed every time an amplification process is performed. The results of the three-wavelength fluorescence detection (the results of the analysis process by the analysis device 2) are displayed on the display of the terminal 3.

In each of steps S1 to S6 of the above-mentioned analysis process, an opening operation (opening the lid) and a closing operation (closing the lid) of each container 50 are performed each time liquid is collected from or dispensed into each container 50. As described above, the analysis device 2 according to this embodiment is equipped with an opening/closing unit 14 equipped with an opening/closing mechanism having a protrusion for automatically opening and closing the lid of each container 50 by touching the lid of each container 50. The control device 20 controls the opening/closing unit 14 to automatically open and close the lid of each container 50 at the timing when it is necessary to open and close the lid of each container 50 in each of steps S1 to S6.

As described above, in the analysis device 2 according to this embodiment, the nozzle 13a of the dispensing unit 12 is configured so that the long tip 53a and the short tip 53b, which is shallower than the long tip 53a, can be detachably attached. Then, with the long tip 53a attached to the nozzle 13a, 25 μL of sample, which is more than the required amount of 5 μL, is aspirated from the sample container 54 and temporarily dispensed into the PCR container 51a. This allows the position of the nozzle 13a to be maintained higher than when the sample is collected from the sample container 54 with the short tip 53b attached to the nozzle 13a, making it difficult for the sample to adhere to the nozzle 13a.

Then, the dispensing tip attached to the nozzle 13a is switched from the long tip 53a to the short tip 53b, and in this state, the required amount of sample, 5 μL, is aspirated from the PCR container 51a and dispensed into the PCR container 51b. Therefore, the accuracy of dispensing the sample can be improved compared to dispensing the required amount of sample, 5 μL, with the long tip 53a attached to the nozzle 13a.

As a result, it is possible to improve the accuracy of dispensing the sample while preventing the sample from adhering to the nozzle 13a of the dispensing unit 12.

<Collision detection mechanism for dispensing tips>
As described above, in the analysis device 2 according to this embodiment, the lid of each container 50 is automatically opened and closed by the opening and closing unit 14 in each step S1 to S6 of the analysis process.

However, there may be cases where the lid of the container 50 cannot be automatically opened even when it is time to open the lid of the container 50 due to some factor, such as a malfunction of the opening/closing unit 14. When the dispensing tip 53 attached to the nozzle 13a of the syringe 13 is lowered toward the container 50 to aspirate a sample or reagent, if the lid of the container 50 remains closed, the tip of the dispensing tip 53 will collide with the lid of the container 50.

In the analysis device 2 according to this embodiment, the dispensing unit 12 is provided with a collision detection mechanism for detecting when the tip of the dispensing tip 53 collides with some other object.

Figure 12 is a diagram showing the internal state of the dispensing unit 12 when the dispensing tip 53 is lowered toward a container 50 with an open lid. Note that Figure 12 shows an example in which a short tip 53b is used as the dispensing tip 53 and a reagent container 52 is used as the container 50.

The dispensing unit 12 is covered by a housing 12a. The housing 12a contains a syringe 13 and a collision detection sensor 80.

The syringe 13 includes a nozzle 13a to which a dispensing tip 53 is attached, a cylinder 13b that includes a plunger (not shown) that is movable along the Z-axis direction, and plates 13c and 13d that are fixed to the cylinder 13b.

The dispensing unit 12 includes a syringe holder 12b fixed to the bottom wall of the housing 12a, and a spring 12c that applies an elastic force between the syringe holder 12b and the syringe 13 (more specifically, a plate 13c fixed to the cylinder 13b of the syringe 13). The syringe holder 12b supports the syringe 13 so that it can move along the Z-axis direction. The syringe 13 is biased vertically downward (negative Z-axis direction) relative to the syringe holder 12b by the elastic force of the spring 12c.

The collision detection sensor 80 is fixed to the side wall of the housing 12a. The collision detection sensor 80 includes a pair of a light-emitting unit 81 and a light-receiving unit 82. When the light-emitting unit 81 is emitting light, the collision detection sensor 80 outputs a signal indicating the intensity of the received light of the light-receiving unit 82 to the control device 20.

The control device 20 determines whether the tip of the dispensing tip 53 has collided with another object based on the light receiving intensity of the light receiving unit 82 obtained from the collision detection sensor 80.

The plate 13d fixed to the syringe 13 has a base portion fixed to the syringe 13 and a tip portion formed in an L-shape. When the tip of the dispensing tip 53 is not colliding with another object, the tip portion of the plate 13d is located between the light emitting portion 81 and the light receiving portion 82 of the collision detection sensor 80 and is positioned so as not to obstruct the optical path from the light emitting portion 81 to the light receiving portion 82. Therefore, as shown in FIG. 12, when the dispensing tip 53 descends toward a container 50 with its lid open, the dispensing tip 53 does not collide with the lid of the container 50, and the optical path from the light emitting portion 81 to the light receiving portion 82 is secured. As a result, the light receiving intensity of the light receiving portion 82 becomes the intensity when the light receiving portion 82 receives light from the light emitting portion 81.

Figure 13 is a diagram showing the internal state of the dispensing unit 12 when the dispensing tip 53 is lowered toward a container 50 with a closed lid. As in Figure 12, Figure 13 also shows an example in which a short tip 53b is used as the dispensing tip 53 and a reagent container 52 is used as the container 50.

When the dispensing tip 53 descends towards a closed container 50, the dispensing tip 53 collides (comes into contact with) the lid of the container 50. If the dispensing tip 53 descends further in this state, the syringe 13 is displaced vertically upward (positive direction of the Z axis) relative to the syringe holder 12b against the elastic force of the spring 12c. This causes the tip portion of the plate 13d fixed to the syringe 13 to be displaced vertically upward, blocking the light path from the light emitter 81 to the light receiver 82. This causes the light receiving intensity of the light receiver 82 to be lower than the intensity when the light receiver 82 is receiving light from the light emitter 81.

Considering that the dispensing unit 12 is equipped with the collision detection mechanism described above, the control device 20 according to this embodiment determines that the tip of the dispensing tip 53 has collided with another object when the light receiving intensity of the light receiving unit 82 is less than a threshold value. Here, the "threshold value" can be set to a value that is a predetermined value lower than the light receiving intensity of the light receiving unit 82 when the light receiving unit 82 is receiving light from the light emitting unit 81, for example.

Figure 14 is a flowchart showing an example of the processing procedure executed by the control device 20 when detecting a collision of the dispensing tip 53.

First, the control device 20 acquires a signal indicating the light receiving intensity of the light receiving unit 82 from the collision detection sensor 80 (step S10).

Next, the control device 20 determines whether the light receiving intensity of the light receiving unit 82 is less than the threshold value (step S12). If the light receiving intensity of the light receiving unit 82 is equal to or greater than the threshold value (NO in step S12), the control device 20 determines that the dispensing tip 53 has not collided with another object (step S14). After that, the control device 20 returns to the process.

On the other hand, if the light receiving intensity of the light receiving unit 82 is less than the threshold value (YES in step S12), the control device 20 determines that the dispensing tip 53 has collided with another object (step S16). In this case, it is assumed that some factor is preventing automatic opening of the container 50 and normal analysis processing, so the control device 20 stops subsequent analysis processing (step S18).

If a collision of the dispensing tip 53 is detected while the dispensing tip 53 is being lowered toward a waste box (not shown) provided below the tip waste section 43, it can be detected that the discarded dispensing tip 53 or the tip holder holding the dispensing tip 53 remains in the waste box.

<Modification of analysis process S1>
In step S1 (sample injection) of the analysis process according to the above embodiment, 25 μL of sample is aspirated by the long tip 53a and temporarily dispensed into the PCR vessel 51a, and then the short tip 53b is used to aspirate 5 μL of sample from the PCR vessel 51a and dispense it into the PCR vessel 51b. That is, by finally aspirating and dispensing the required amount of 5 μL of sample using the short tip 53b, a minute amount of sample such as 5 μL is accurately dispensed into the PCR vessel 51b.

However, when the sample is a highly viscous liquid such as saliva, using the short tip 53b to aspirate the sample may result in an insufficient amount of sample being aspirated or the sample may not be aspirated due to the small opening diameter at the tip of the short tip 53b, which may result in the required amount of 5 μL of sample not being aspirated accurately. Furthermore, in the analysis process described in the above embodiment, it is difficult to confirm whether the sample has been properly dispensed.

In view of the above, in this modified example, the opening diameter at the tip of the long tip 53a is larger than the opening diameter at the tip of the short tip 53b, and the required volume of 5 μL of sample is aspirated and dispensed using the long tip 53 rather than the short tip 53b.

Figure 15 is a diagram showing the flow of the process (first sample injection process) of dispensing 5 μL of sample into a PCR container 51b in step S1a according to one embodiment of this modified example. The control device 20 first attaches the long tip 53a to the nozzle 13a of the syringe 13.

Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to aspirate the required amount of sample, 5 μL, from the sample container 54 using the long tip 53a and dispense it into the PCR container 51b, as shown by line L11 in FIG. 15.

In this manner, in step S1a of this modified example, the required volume of 5 μL of sample is aspirated and dispensed using the long tip 53, which has a larger opening diameter than the short tip 53b. Therefore, compared to when the required volume of 5 μL of sample is aspirated and dispensed using the short tip 53b, it is possible to prevent a highly viscous sample such as saliva from being unable to be aspirated or an insufficient amount being aspirated. As a result, even when the sample is a highly viscous liquid such as saliva, the required volume of 5 μL of sample can be aspirated more appropriately.

Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to aspirate 25 μL of sample for visual confirmation from the PCR container 51a using the long tip 53a and dispense it into the PCR container 51a, as shown by line L12 in Figure 7.

In this manner, in step S1a according to this modified example, 25 μL of sample for visual confirmation is dispensed into PCR container 51a. As a result, after all steps of the analysis process are completed, the operator can visually check the amount of sample in PCR container 51a to confirm whether the sample has been properly dispensed. That is, in step S1a according to this modified example, in view of the fact that the required amount of 5 μL is a minute amount and difficult to visually check, 25 μL of sample, which is more than the required amount of 5 μL, is dispensed into PCR container 51a as a sample for visual confirmation. Therefore, it is easier for the operator to visually check the amount of sample in PCR container 51a compared to when the sample for visual confirmation is a minute amount of 5 μL.

As a method for visually checking that the sample volume in PCR container 51a is 25 μL after all steps of the analysis process are completed, for example, a method is envisaged in which a 25 μL volume mark is placed on the wall of PCR container 51a and this mark is compared with the sample volume in PCR container 51a. As another method, a method is envisaged in which, taking into consideration that the amount of reagent mixture in PCR container 51b adjacent to PCR container 51a is 25 μL, the amount of reagent mixture in PCR container 51b is compared with the sample volume in PCR container 51a.

If it can be visually confirmed that the sample volume in PCR container 51a is 25 μL after all steps of the analysis process are completed, it can be inferred that 5 μL of sample has been properly dispensed into PCR container 51b.

After dispensing 25 μL of sample for visual inspection into PCR container 51a, controller 20 controls dispensing unit 12 and moving devices 4 and 5 to discard long tip 53a in tip disposal unit 43 and attach the first short tip 53b to nozzle 13a of syringe 13 in preparation for the next step S2. The processing from step S2 onwards is the same as in the above-mentioned embodiment.

Figure 16 is a diagram showing the flow of the process (second sample injection process) of dispensing 5 μL of sample into a PCR container 51b in step S1b according to another aspect of this modified example. The control device 20 first attaches the long tip 53a to the nozzle 13a of the syringe 13.

Then, as shown by line L21 in FIG. 16, the control device 20 uses the long tip 53a to aspirate a total of 30 μL of sample from the sample container 54, including the required amount of 5 μL and 25 μL for visual confirmation.

Then, the control device 20 controls the dispensing unit 12 and the moving devices 4 and 5 to dispense the required amount of 5 μL of the sample into the PCR container 51b, as shown by line L22 in FIG. 16, out of the total amount of 30 μL of sample aspirated into the long tip 53a, and to dispense the remaining 25 μL for visual confirmation into the PCR container 51a, as shown by line L23 in FIG. 16.

In this type of step S1b, the same effect as in step S1a described above can be achieved.

In steps S1a and S1b, an example is shown in which the required amount of 5 μL of sample is dispensed into PCR container 51b, and then 25 μL of sample for visual confirmation is dispensed into PCR container 51a. However, it is also possible to dispense the required amount of 5 μL of sample into PCR container 51b after dispensing 25 μL of sample for visual confirmation into PCR container 51a.

[Aspects]
It will be understood by those skilled in the art that the above-described embodiment and its modifications are specific examples of the following aspects.

(1) The analytical device according to the present disclosure includes a tip used for dispensing liquid, a nozzle configured to allow the tip to be detachably attached, a dispensing device that dispenses liquid into a plurality of containers via the tip attached to the nozzle, and a control device that controls the dispensing device. The tips include a first tip and a second tip that is shallower than the first tip. The plurality of containers include a specimen container in which a specimen is placed, and a first reaction container and a second reaction container that are shallower than the specimen container. The control device controls the dispensing device to aspirate a second amount of specimen, which is greater than the first amount, from the specimen container with the first tip attached to the nozzle and dispense the specimen into the first reaction container, and to aspirate the first amount of specimen from the first reaction container with the second tip attached to the nozzle and dispense the specimen into the second reaction container.

According to the analysis device described in paragraph 1, the nozzle of the dispensing device is configured so that a first tip (long tip) and a second tip (short tip) that is shallower than the first tip can be detachably attached. Then, with the first tip (long tip) attached to the nozzle, a second amount of sample that is greater than a first amount (e.g., a required amount) is aspirated from the sample container and dispensed into a first reaction container. This allows the nozzle to be kept higher than when the sample is aspirated from the sample container with the second tip (short tip) attached to the nozzle, making it difficult for the sample to adhere to the nozzle.

Then, with the second tip (short tip) attached to the nozzle, a first amount (e.g., the required amount) of sample is aspirated from the first reaction container and dispensed into the second reaction container. This improves the accuracy of dispensing the sample compared to when the first amount of sample is aspirated with the first tip (long tip) attached to the nozzle.

As a result, it is possible to improve the accuracy of dispensing the sample while preventing the sample from adhering to the nozzle of the dispensing device.

(Clause 2) In the analysis device described in paragraph 1, the first tip has a first opening having a first diameter, and the second tip has a second opening having a second diameter smaller than the first diameter. The nozzle has a first portion having a diameter that fits into the first opening of the first tip, and a second portion that is located closer to the tip than the first portion and has a diameter that fits into the second opening of the second tip.

According to the analysis device described in paragraph 2, a nozzle can be configured to which the first chip and the second chip can be detachably attached by providing the nozzle with a first part that fits into the first chip and a second part that fits into the second chip.

(Clause 3) In the analytical device described in paragraph 1 or 2, each of the multiple containers has an openable and closable lid. The analytical device further includes a capping device that opens the containers. The control device controls the dispensing device to dispense liquid into the containers that have been opened by the capping device.

The analytical device described in paragraph 3 allows liquid to be dispensed and containers to be opened without manual intervention by an operator.

(4) In the analysis device described in any one of 1 to 3, the multiple containers include a first reagent container containing a first reagent in an amount including a first usage amount and a first excess amount, a second reagent container containing a second reagent in an amount including a second usage amount and a second excess amount, a third reagent container containing a third reagent in an amount including a third usage amount and a third excess amount, and a fourth reagent container containing a fourth reagent including a fourth usage amount and an excess amount less than the first to third excess amounts. The control device controls the dispensing device to aspirate the first usage amount of the first reagent from the first reagent container and dispense it into the second reaction container, aspirate the second usage amount of the second reagent from the second reagent container and dispense it into the fourth reagent container, aspirate the third usage amount of the third reagent from the third reagent container and dispense it into the fourth reagent container, and aspirate a mixed liquid including the second reagent, the third reagent, and the fourth reagent from the fourth reagent container and dispense it into the second reaction container.

The analytical device described in paragraph 4 can reduce the amount of the fourth reagent contained in the fourth reagent container used while preventing empty suction when aspirating the first to fourth reagents from the first to fourth reagent containers, respectively.

(5) In the analysis device described in any one of paragraphs 1 to 4, the dispensing device is equipped with a collision detection mechanism for detecting when the tip collides with another object.

The analysis device described in paragraph 5 can detect when the chip collides with another object.

(6) In the analysis device described in any one of paragraphs 1 to 5, gene analysis is performed using the polymerase chain reaction.

The analysis device described in paragraph 6 can improve the accuracy of dispensing samples while preventing samples from adhering to the nozzle of a dispensing device in genetic analysis using the polymerase chain reaction.

(7th paragraph) The reagent kit according to the present disclosure is a reagent kit applicable to the analytical device described in any one of paragraphs 1 to 5, and includes a plurality of containers and a packaging material for packaging the plurality of containers. The plurality of containers are provided including a first reagent container containing a first reagent in an amount including a first usage amount and a first excess amount for preventing empty aspiration, a second reagent container containing a second reagent in an amount including a second usage amount and a second excess amount for preventing empty aspiration, a third reagent container containing a third reagent in an amount including a third usage amount and a third excess amount for preventing empty aspiration, and a fourth reagent container containing a fourth reagent including a fourth usage amount and an excess amount less than the first to third excess amounts.

The reagent kit described in paragraph 7 can prevent empty aspirates when aspirating the first to fourth reagents from the first to fourth reagent containers, respectively, while reducing the amount of the fourth reagent contained in the fourth reagent container used.

(Clause 8) The analytical device according to the present disclosure includes a tip used for dispensing liquid, a nozzle configured to detachably attach the tip, and a dispensing device that dispenses liquid into multiple containers via the tip attached to the nozzle, and a control device that controls the dispensing device. The tips include a first tip and a second tip having a smaller opening diameter at the tip than the first tip. The multiple containers include a specimen container containing a specimen, and a first reaction container and a second reaction container that are shallower than the specimen container. The control device controls the dispensing device to dispense a first amount of the specimen aspirated from the specimen container using the first tip into the second reaction container, and to dispense a second amount of the specimen aspirated from the specimen container using the first tip into the first reaction container, the second amount being greater than the first amount.

(Clause 9) In the analytical device described in clause 8, the control device controls the dispensing device to aspirate a first amount of sample from the sample container using the first tip and dispense the first amount of sample into the second reaction container, and to aspirate a second amount of sample from the sample container using the first tip and dispense the second amount of sample into the first reaction container.

(Clause 10) In the analytical device described in clause 8, the control device controls the dispensing device to aspirate a total of a first amount and a second amount of sample from a sample container using the first tip, and to dispense the first amount of sample from the total amount of sample aspirated into the first tip into a second reaction container and to dispense the second amount of sample into the first reaction container.

According to the analytical device described in paragraphs 8 to 10, even if the sample is a highly viscous liquid such as saliva, the first amount (e.g., the required amount) of the sample can be appropriately dispensed into the second reaction container. Furthermore, by visually checking whether the second amount (e.g., a visible amount) of the sample is contained in the first reaction container, it is possible to check whether the sample has been appropriately dispensed.

The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present invention is indicated by the claims, not by the description of the embodiments above, and is intended to include all modifications within the meaning and scope of the claims.

1 Analysis system, 2 Analysis device, 3 Terminal, 4, 5 Moving device, 10 Inspection device, 11 Optical unit, 12 Dispensing unit, 13 Syringe, 13a Nozzle, 14 Opening and closing unit, 16 Irradiation unit, 20 Control device, 30 Temperature control device, 40 Holding device, 41 Temperature control section, 42 Holding section, 43 Tip disposal section, 50 Container, 51, 51a, 51b, 51c, 51d PCR container, 52, 52a, 52b, 52c, 52d Reagent container, 53 Dispensing tip, 53a Long tip, 53b Short tip, 54 Sample container, 55 Packaging material.

Claims (7)

A tip used for dispensing liquid;
a dispensing device including a nozzle to which the tip is detachably attached, the dispensing device dispensing liquid into a plurality of containers through the tip attached to the nozzle;
A control device for controlling the dispensing device,
The tip includes a first tip and a second tip having a depth shallower than that of the first tip,
The plurality of containers include a specimen container in which a specimen is placed, and a first reaction container and a second reaction container each having a depth shallower than that of the specimen container;
the dispensing device is configured such that a dispensing accuracy when the first tip is attached to the nozzle is lower than a dispensing accuracy when the second tip is attached to the nozzle,
When dispensing a first amount of the specimen from the specimen container to the second reaction container, the control device
With the specimen in the specimen container, and with the first tip attached to the nozzle, aspirating a second amount of the specimen from the specimen container, the second amount being greater than the first amount, and dispensing the second amount into the first reaction container;
After dispensing the second amount into the first reaction vessel, the tip attached to the nozzle is switched from the first tip to the second tip;
An analytical apparatus that controls the dispensing device so as to aspirate the first amount of the sample from the first reaction container with the second tip attached to the nozzle and dispense the first amount into the second reaction container. the first tip has a first opening having a first diameter;
the second tip has a second opening having a second diameter smaller than the first diameter;
The nozzle is
a first portion having a diameter that fits into the first opening of the first tip;
The analysis device according to claim 1 , further comprising: a second portion that is provided closer to the tip than the first portion and has a diameter that fits into the second opening of the second tip. Each of the plurality of containers has an openable and closable lid,
The analysis device further includes an uncapper that uncaps the container,
The analytical device according to claim 1 , wherein the control device controls the dispensing device to dispense liquid into a container that has been opened by the cap removing device. The plurality of containers include a first reagent container containing a first reagent in an amount including a first usage amount and a first excess amount, a second reagent container containing a second reagent in an amount including a second usage amount and a second excess amount, a third reagent container containing a third reagent in an amount including a third usage amount and a third excess amount, and a fourth reagent container containing a fourth reagent including a fourth usage amount and an excess amount less than the first to third excess amounts;
The control device includes:
Aspirating the first amount of the first reagent from the first reagent container and dispensing it into the second reaction container;
aspirating the second amount of the second reagent from the second reagent container and dispensing it into the fourth reagent container;
aspirating the third amount of the third reagent from the third reagent container and dispensing it into the fourth reagent container;
The analytical apparatus according to any one of claims 1 to 3, wherein the dispensing device is controlled so as to aspirate a mixed liquid containing the second reagent, the third reagent, and the fourth reagent from the fourth reagent container and dispense the mixed liquid into the second reaction container. The analysis device according to any one of claims 1 to 4, wherein the dispensing device is equipped with a collision detection mechanism for detecting when the tip collides with another object. The analysis device according to any one of claims 1 to 5, which performs gene analysis using the polymerase chain reaction. A reagent kit applicable to the analysis device according to claim 1,
The plurality of containers;
and a packaging material for packaging the plurality of containers,
The plurality of containers include:
a first reagent container containing a first reagent in an amount including a first usage amount and a first excess amount for preventing empty aspiration;
a second reagent container containing a second reagent in an amount including a second usage amount and a second excess amount for preventing empty aspiration;
a third reagent container containing a third reagent in an amount including a third amount to be used and a third excess amount for preventing empty aspiration;
The reagent kit is provided in a state including a fourth reagent container containing a fourth reagent including a fourth usage amount and an excess amount less than the first to third excess amounts.

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