Liquid processing device, nucleic acid extraction device, and gene testing device

Abstract

A liquid treatment device 4 comprises: a constant temperature part 6 that is provided with a container-holding part 5 for holding a liquid container 2 housing a liquid and has a plurality of constant temperature regions 6a-6c having different set temperatures; a dispenser 3 for aspirating or discharging the liquid housed in the liquid container 2; a heat transfer part 7 for heating or cooling the constant temperature part 6; a temperature sensor part 11 for outputting data related to the temperature of the constant temperature part 6; a power supply part 13 for supplying power to the heat transfer part 7; a control part 12 for controlling the power supplied by the power supply part 13 to the heat transfer part 7 based on the output of the temperature sensor part 11; and first heat resistance parts 8a, 8b that separate the constant temperature regions 6a-6c. The first heat resistance parts 8a, 8b have heat resistance values larger than that of the constant temperature part 6 and have heat resistance values such that, when the temperature of one constant temperature region separated by the first heat resistance parts 8a, 8b becomes the set temperature of that one constant temperature region, the temperature of the other constant temperature region separated by the first heat resistance parts becomes the set temperature of that other constant temperature region.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to a liquid processing apparatus, a nucleic acid extraction apparatus, and a genetic testing apparatus. BACKGROUND ART

[0002] In a genetic testing apparatus, nucleic acid is amplified by a method such as the polymerase chain reaction (PCR), and the nucleic acid contained in a sample is extracted before the test is performed. In nucleic acid extraction by the Magtration method using magnetic particles as a carrier, nucleic acid is extracted through: a liquid processing step of solubilizing proteins in a sample; a liquid processing step of binding magnetic particle carriers to phosphate groups of nucleic acids; a liquid processing step of removing impurities from the magnetic particles bound with nucleic acids; and a liquid processing step of eluting nucleic acids from the magnetic particles. At this time, the optimal processing temperature differs for each liquid processing step depending on the type of sample, the type of reagent used, and differences in processing protocols. Therefore, in order to perform nucleic acid extraction for highly reliable genetic testing, a liquid processing apparatus capable of rapidly changing the temperature of liquid in accordance with the content of liquid processing is required.

[0003] Regarding temperature control in liquid processing apparatuses, Patent Document 1 discloses a genetic testing apparatus including heat sources individually provided for a plurality of test containers containing samples, and a control unit that controls the heat sources to individually adjust the temperature of the samples.

[0004] Patent Document 2 discloses a laboratory thermostat including at least two or more temperature control devices in thermally conductive contact with a temperature control block, for setting different portions of the temperature control block provided with a storage section for storing a container containing a liquid sample to different temperatures. PRIOR ART DOCUMENTS PATENT DOCUMENTS

[0005] Patent Document 1 Japanese Unexamined Patent Publication No. 2012-228212 Patent Document 2 Special Publication No. 2000-504231 [Overview of the project] [Problems that the invention aims to solve]

[0006] In the gene testing apparatus described in Patent Document 1, when adjusting the temperature of samples in multiple test containers, the structure requires one heat source for heating and cooling the heat transfer section (heat conduction section) and one control unit for controlling the heat source for each heat transfer section (heat conduction section) that holds the individual test containers containing the samples. Therefore, the incorporation of multiple temperature control systems leads to increased complexity of the temperature control system structure and increased costs. Furthermore, because the structure is separated to minimize heat transfer between multiple heat transfer sections (heat conduction sections) with different temperatures, the size of the apparatus becomes a challenge. In addition, because the structure is designed to change the temperature by heating and cooling the heat transfer section (heat conduction section) when the optimal temperature for the sample reaction changes, the time required for the temperature to rise and fall of the apparatus becomes a challenge in improving throughput.

[0007] The laboratory thermostat described in Patent Document 2 requires multiple temperature control devices to maintain different temperatures at different points in a temperature control block that houses multiple containers for liquid samples. Therefore, incorporating multiple temperature control systems leads to increased structural complexity and higher costs, which are challenges.

[0008] The problem that this invention aims to solve is to provide a compact liquid processing apparatus that can utilize multiple constant temperature sections at optimal temperatures for liquid processing, without necessarily requiring multiple temperature control systems, in a liquid processing apparatus that processes liquids at multiple temperatures. [Means for solving the problem]

[0009] To solve the above problems, the liquid processing apparatus of the present disclosure includes a container holding unit for holding a liquid container containing liquid, a constant temperature unit having a plurality of constant temperature regions with different set temperatures, a dispensing machine for sucking or discharging liquid contained in the liquid container, a heat transfer unit for heating or cooling the constant temperature unit, a temperature sensor unit for outputting data relating to the temperature of the constant temperature unit, a power supply unit for supplying power to the heat transfer unit, a control unit for controlling the power supplied by the power supply unit to the heat transfer unit based on the output of the temperature sensor unit, and a first thermal resistance unit separating at least two constant temperature regions, wherein the first thermal resistance unit has a greater thermal resistance value than the constant temperature unit, and has a thermal resistance value such that when the temperature of one constant temperature region separated by the first thermal resistance unit reaches the set temperature of that one constant temperature region, the temperature of the other constant temperature region separated by the first thermal resistance unit reaches the set temperature of that other constant temperature region.

[0010] Furthermore, the nucleic acid extraction apparatus of this disclosure includes the liquid processing apparatus described above.

[0011] Furthermore, the gene testing apparatus of this disclosure includes the liquid processing apparatus described above. [Effects of the Invention]

[0012] The liquid processing apparatus described herein allows for the use of multiple constant temperature sections at optimal temperatures for liquid processing, without necessarily requiring multiple temperature control systems, and can be provided in a compact form. This is expected to improve liquid processing throughput, simplify temperature control systems, and reduce manufacturing costs. Furthermore, miniaturizing the liquid processing apparatus allows for the use of multi-well plates as liquid containers, which is expected to reduce the man-hours and risk of misidentification associated with changing liquid containers. [Brief explanation of the drawing]

[0013] [Figure 1] Schematic diagram showing the cross-sectional structure of the liquid processing apparatus of Example 1 [Figure 2]Schematic diagram of the constant temperature region 6a, constant temperature region 6b, constant temperature region 6c, and ambient temperature when the temperature sensor unit 11 is installed in the constant temperature region 6b of the liquid processing apparatus of Example 1. [Figure 3] Schematic diagram of the constant temperature region 6a, constant temperature region 6b, constant temperature region 6c, and ambient temperature when the temperature sensor unit 11 is installed in the constant temperature region 6a of the liquid processing apparatus of Example 1. [Figure 4] A schematic diagram showing an example of the structure of the first thermal resistance sections 8a and 8b of the liquid processing apparatus of Example 1. [Figure 5] A schematic diagram showing an example of the structure of the first thermal resistance sections 8a and 8b of the liquid processing apparatus of Example 1. [Figure 6] A schematic diagram showing an example of the structure of the first thermal resistance sections 8a and 8b of the liquid processing apparatus of Example 1. [Figure 7] Schematic diagram showing the cross-sectional structure of the liquid processing apparatus in Example 2 [Figure 8] Schematic diagram showing the cross-sectional structure of the liquid processing apparatus of Example 3 [Figure 9] Schematic diagram showing the cross-sectional structure of the third thermal resistance section 15a and 15b of the liquid processing apparatus of Example 4. [Figure 10] A diagram showing a nucleic acid extraction apparatus and a gene testing apparatus equipped with a liquid processing apparatus. [Modes for carrying out the invention]

[0014] In all the figures used to illustrate this embodiment, components having the same function are denoted by the same reference numerals, and repeated explanations may be omitted. Furthermore, the present invention is not to be construed as being limited to the embodiments described below. The present invention is defined by the appended claims, but it will be readily apparent to those skilled in the art that its specific configuration can be modified without departing from its spirit or purpose.

[0015] Positions, sizes, shapes, ranges, and the like of respective components shown in drawings and the like may not represent actual positions, sizes, shapes, ranges, and the like in order to facilitate understanding of the invention. Therefore, the present invention is not necessarily limited to the positions, sizes, shapes, ranges, and the like disclosed in the drawings and the like.

[0016] Components expressed in the singular form in this specification shall include the plural form unless clearly indicated otherwise by the context. EXAMPLE

[0017] One embodiment of the liquid processing apparatus of Example 1 will be described. Fig. 1 is a schematic diagram showing a cross-sectional structure of the liquid processing apparatus of Example 1. In the present embodiment, a structure in which three constant temperature regions are set to different set temperatures respectively by one temperature control system will be described.

[0018] A liquid 1 is contained in a liquid container 2, and is aspirated and discharged by a dispenser 3 to be dispensed. The liquid processing apparatus 4 comprises the dispenser 3, a constant temperature section 6 provided with a container holding section 5 for holding the liquid container 2, a heat transfer section 7, first thermal resistance sections 8a and 8b, a heat dissipation section 9, a heat insulation section 10, a temperature sensor section 11, a control section 12, and a power supply section 13.

[0019] The liquid container 2 is provided with a plurality of regions for containing the liquid 1. For the liquid container 2, one in which regions for containing the liquid 1 are arranged in one direction may be used, or a multi-well plate in which the regions are arranged in two directions may be used. In the present embodiment, it is assumed that a multi-well plate is used as the liquid container 2.

[0020] The constant temperature section 6 is provided with a set temperature. The set temperature may be higher or lower than the ambient temperature. The constant temperature section 6 is divided into multiple regions with different set temperatures. In this embodiment, the constant temperature section 6 is divided into three regions with different set temperatures, which are designated as constant temperature region 6a, constant temperature region 6b, and constant temperature region 6c. For example, the set temperatures of constant temperature region 6a, constant temperature region 6b, and constant temperature region 6c are 80°C, 70°C, and 60°C, respectively. Each constant temperature region 6a to 6c may hold one or more regions of the container holding section 5. Each constant temperature region 6a to 6c is preferably made of a material with high thermal conductivity and excellent temperature uniformity. This allows for the processing of liquids within multiple regions at the same temperature, even if the constant temperature regions 6a to 6c hold multiple regions of the container holding section 5. The constant temperature section 6 is preferably made of, for example, copper, aluminum, or an alloy thereof. Furthermore, all of the constant temperature regions 6a to 6c may be composed of the same material, or at least two of the constant temperature regions 6a to 6c may be composed of different materials.

[0021] The heat transfer unit 7 heats or cools the constant temperature unit 6. If the set temperatures of the constant temperature regions 6a to 6c are higher than the ambient temperature, a heat-generating component such as a heater can be used in the heat transfer unit 7. If the set temperatures of the constant temperature regions 6a to 6c are lower than the ambient temperature, the heat transfer unit 7 can be cooled by using a Peltier module or the like. In this embodiment, there are three constant temperature regions 6a to 6c with different set temperatures, but there is only one heat transfer unit 7. The heat transfer unit 7 is in contact with the constant temperature region 6a, which has a set temperature furthest from the ambient temperature. The heat transfer unit 7 does not necessarily have to be in contact with the constant temperature region 6a; it is sufficient if it can heat or cool the constant temperature region 6a.

[0022] The first thermal resistance section 8a separates constant temperature regions 6a and 6b, which have different set temperatures, and the first thermal resistance section 8b separates constant temperature regions 6b and 6c, which have different set temperatures. The first thermal resistance sections 8a and 8b adjust the amount of heat transferred from the constant temperature region with the higher set temperature to the constant temperature region with the lower set temperature, and are pre-equipped with the thermal resistance value necessary for both constant temperature regions to reach the set temperature. In this embodiment, the first thermal resistance section 8a has a thermal resistance value such that when constant temperature region 6a is at the set temperature of 80°C due to heating by the heat transfer section 7, constant temperature region 6b is at the set temperature of 70°C. Also, the first thermal resistance section 8b has a thermal resistance value such that when constant temperature region 6b is at the set temperature of 70°C due to heat transfer via the first thermal resistance section 8a, constant temperature region 6c is at the set temperature of 60°C.

[0023] The heat dissipation unit 9 can be provided in a constant temperature region 6b or 6c other than the constant temperature region 6a where the set temperature is furthest from the ambient temperature. In this embodiment, the heat dissipation unit 9 is installed in the constant temperature region 6c, among the constant temperature regions 6a to 6c, where the set temperature is closest to the ambient temperature. For example, cooling fins are used for the heat dissipation unit 9. In this case, the heat dissipation unit 9 has heat dissipation performance such that constant temperature regions 6a, 6b, and 6c reach the set temperature, along with the thermal resistance values ​​of the first thermal resistance units 8a and 8b.

[0024] In order to create a large temperature difference between constant temperature regions 6a, 6b, and 6c, it is necessary to increase the thermal resistance values ​​of the first thermal resistance section 8a and the first thermal resistance section 8b. To increase the thermal resistance values, it is necessary to either decrease the apparent thermal conductivity of the first thermal resistance section 8a and the first thermal resistance section 8b or increase their thickness. In this embodiment, when a multiwell plate is used as the liquid container 2 and the distance between the container holding sections 5 is determined by the dimensions of the multiwell plate, it is difficult to freely change the thickness of the first thermal resistance section 8a and the first thermal resistance section 8b, and it may not be possible to create the set temperature difference between constant temperature regions 6a, 6b, and 6c. Therefore, by providing a heat dissipation section 9 in constant temperature region 6c to promote heat exchange with the environment, the temperatures of constant temperature regions 6b and 6c can be brought closer to the ambient temperature. Then, when constant temperature region 6a is at the set temperature, it becomes easier to increase the temperature difference between constant temperature regions 6a, 6b, and 6c. In the example shown in Figure 1, the heat dissipation unit 9 is provided in the constant temperature region 6c, but the heat dissipation unit 9 may also be provided in both the constant temperature region 6b and the constant temperature region 6c. The heat dissipation performance of the heat dissipation unit 9 provided in the constant temperature region 6b and the heat dissipation performance of the heat dissipation unit 9 provided in the constant temperature region 6c may be the same or different.

[0025] The heat-insulating section 10 is configured to cover the constant temperature section 6, the heat transfer section 7, and the first thermal resistance sections 8a and 8b. This allows the constant temperature section 6 to maintain temperature uniformity. Furthermore, by suppressing heat dissipation to the environment, the energy consumption of the heat transfer section 7 can be kept low.

[0026] The temperature sensor unit 11 measures the temperature of the constant temperature unit 6 and outputs data related to the temperature of the constant temperature unit 6 to the control unit 12. Based on the output of the temperature sensor unit 11, the control unit 12 controls the power supplied by the power supply unit 13 to the heat transfer unit 7 so that the temperature of the constant temperature region 6b where the temperature sensor unit 11 is installed reaches the set temperature. In this embodiment, the temperature sensor unit 11 is installed in constant temperature region 6b, which is in the middle of the constant temperature regions 6a to 6c, and the power supplied to the heat transfer unit 7 is controlled so that the constant temperature region 6b reaches the set temperature of 70°C. The constant temperature region where the temperature sensor unit 11 is installed may be constant temperature region 6a or constant temperature region 6c.

[0027] Figure 2 shows schematic diagrams of the temperatures of constant temperature regions 6a, 6b, 6c, and the ambient temperature. In this embodiment, the constant temperature regions 6a, 6b, and 6c are structured to maintain set temperatures of 80°C, 70°C, and 60°C, respectively, at an ambient temperature of 20°C. Now, let's consider the case where the ambient temperature fluctuates by ±10°C from 20°C. Constant temperature region 6b is controlled to a set temperature of 70°C by the function of the temperature sensor unit 11, even if the ambient temperature fluctuates. On the other hand, the temperatures of constant temperature regions 6a and 6c fluctuate from their set temperatures in accordance with the fluctuations in ambient temperature. If the degree of temperature fluctuation between constant temperature region 6a and constant temperature region 6c is E_6a and E_6c, respectively, then as shown in Figure 2, E_6a and E_6c are approximately the same.

[0028] As another example of the arrangement of the temperature sensor unit 11, consider the case where the temperature sensor unit 11 is installed in the constant temperature region 6a, which is the furthest from the ambient temperature and heated by the heat transfer unit 7, and the power supplied to the heat transfer unit 7 is controlled so that the constant temperature region 6a reaches the set temperature of 80°C. A schematic diagram of the temperatures of constant temperature region 6a, constant temperature region 6b, constant temperature region 6c, and (Ambient) in this case is shown in Figure 3. Consider the case where the ambient temperature varies from 20°C to ±10°C. The constant temperature region 6a is controlled to the set temperature even if the ambient temperature varies due to the function of the temperature sensor unit 11. The temperatures of constant temperature regions 6b and 6c vary from the set temperature in accordance with the variation in ambient temperature. If the degree of temperature variation between constant temperature region 6b and constant temperature region 6c is E_6b and E_6c, respectively, then as shown in Figure 3, it can be seen that E_6c is larger than E_6b.

[0029] To prevent the temperature of any of the three constant temperature regions 6a to 6c from deviating significantly from the set temperature when the ambient temperature changes, it is effective to install the temperature sensor unit 11 in the intermediate constant temperature region 6b. On the other hand, if it is necessary to prioritize and precisely control the temperature of one of the three constant temperature regions 6a to 6c, it is effective to install the temperature sensor unit 11 in that constant temperature region. These measures are effective in preventing variations in ambient temperature from reducing the temperature control capability for liquid processing, especially in configurations where the number of temperature control systems is small compared to the number of constant temperature regions 6a to 6c with different set temperatures.

[0030] If the temperature of any of the multiple constant temperature regions 6a to 6c falls outside the set temperature due to factors such as changes in ambient temperature, the control unit 12 may adjust the power supplied by the power supply unit 13 to the heat transfer unit 7 so that the temperature of the constant temperature region where liquid processing is performed reaches the set temperature. For example, when performing liquid processing in constant temperature region 6c with a set temperature of 60°C, the control unit 12 controls the power supply unit 13 to supply the heat transfer unit 7 with the power necessary for constant temperature region 6c to reach the set temperature of 60°C. Subsequently, when performing liquid processing in constant temperature region 6a with a set temperature of 80°C, the control unit 12 may adjust the power supply unit 13 to supply the heat transfer unit 7 with the power necessary for constant temperature region 6a to reach the set temperature of 80°C. In this case, the amount of power required for each constant temperature region to reach the set temperature can be measured and recorded in advance. For example, the ambient temperature can be measured using a temperature sensor (not shown), and the amount of power required for a certain constant temperature unit 6 to reach the set temperature can be recorded for each ambient temperature. In this embodiment, since the temperatures of the constant temperature regions 6a to 6c, which have different set temperatures, are near their respective set temperatures, it is expected that the temperature of the constant temperature section 6 can be brought closer to the set temperature with a short temperature change time.

[0031] The first thermal resistance sections 8a and 8b adjust the amount of heat transferred from the higher-temperature section to the lower-temperature section of the separating constant-temperature regions, and are pre-equipped with the thermal resistance value necessary for both constant-temperature regions to reach the set temperature. An example of the structure of the first thermal resistance sections 8a and 8b is shown in Figure 4. As an example of the structure of the first thermal resistance section 8a or 8b, a single thermal resistance member 801 may be used to provide the desired thermal resistance value. As the thermal resistance member 801, for example, a uniform solid material with a lower thermal conductivity than the constant-temperature section 6 can be selected and placed. From the viewpoint of creating a temperature difference between the separating constant-temperature regions, a solid material with a lower thermal conductivity than the constant-temperature section 6 is desirable. Examples include resin-based materials, rubber-based materials, and insulating materials. As the thermal resistance member 801, in addition to solid materials, a gas layer may also be used. Both the first thermal resistance sections 8a and 8b may be a single thermal resistance member 801, or either the first thermal resistance section 8a or 8b may be a single thermal resistance member 801.

[0032] As an example of another structure for the first thermal resistance sections 8a and 8b, a desired thermal resistance value may be provided by a convex portion 802 and a concave portion 803 provided on the surface of the constant temperature region. In this structure, the contact area between the convex portion 802 provided on the surface of one constant temperature region and the surface of the other constant temperature region can be changed to adjust the solid conduction heat transfer by the convex portion 802 and provide a desired thermal resistance value. The concave portion 803 may be made of a solid material with appropriate thermal conductivity or a gas layer, similar to the thermal resistance member 801. Alternatively, the constant temperature section 6 may be made as a single component and holes may be machined in the locations corresponding to the concave portion 803 to create a structure equivalent to the convex portion 802 and concave portion 803. Both the first thermal resistance sections 8a and 8b may have a structure with a convex portion 802 and a concave portion 803, or either the first thermal resistance section 8a or 8b may have a structure with a convex portion 802 and a concave portion 803.

[0033] Figure 5 shows another example of the structure of the first thermal resistance sections 8a and 8b. As an example of another structure of the first thermal resistance sections 8a and 8b, a spacer 804 and a fastening member 805 may be used to provide a desired thermal resistance value. The spacer 804 and the fastening member 805 can not only fix the separating constant temperature regions in a predetermined relative position, but can also play a role in adjusting solid conductive heat transfer. As a method of adjusting solid conductive heat transfer with the spacer 804, the heat transfer area may be changed by changing the size of the spacer 804, the heat transfer area may be changed by changing the number of spacers 804, or the spacer 804 may be made of a material with different thermal conductivity. For example, when fastening the spacer 804 with the fastening member 805, a resin washer with low thermal conductivity can be used. As a method of adjusting solid conductive heat transfer with the fastening member 805, the fastening member 805 may be made of a material with different thermal conductivity. For example, a resin screw can be used as the fastening member 805. Both the first thermal resistance sections 8a and 8b may have a structure in which a spacer 804 and a fastening member 805 are present, or either the first thermal resistance section 8a or 8b may have a structure in which a spacer 804 and a fastening member 805 are present. Alternatively, the spacer 804 used as the first thermal resistance section 8a and the spacer 804 used as the first thermal resistance section 8b may be fixed together with a single fastening member 805.

[0034] Figure 6 shows another example of the structure of the first thermal resistance sections 8a and 8b. As an example of another structure of the first thermal resistance sections 8a and 8b, a desired thermal resistance value may be provided by a thermal radiation section 806 and a thermal radiation section 807 provided on opposing surfaces of the constant temperature region. In this structure, a desired thermal resistance value is obtained by adjusting the radiant heat transfer between the surfaces of the constant temperature region. The thermal radiation section 806 or the thermal radiation section 807 may be subjected to a surface treatment that changes the emissivity. For example, the thermal radiation section 806 or the thermal radiation section 807 may use a radioactive paint or have an oxide film formed, such as anodized aluminum. Alternatively, the radiant heat transfer may be adjusted by the area to which the surface treatment is applied to obtain a desired thermal resistance value. In the example in Figure 6, the thermal radiation section 806 and the thermal radiation section 807 are formed on both opposing surfaces of the constant temperature region, but the thermal radiation section may be provided on only one surface. Furthermore, both the first thermal resistance sections 8a and 8b may have a structure in which a thermal radiation section 806 or 807 is present, or either the first thermal resistance section 8a or 8b may have a structure in which a thermal radiation section 806 or 807 is present.

[0035] As an example of another structure for the first thermal resistance sections 8a and 8b, a sealed section 808 may be formed, and the desired thermal resistance value may be achieved by reducing the pressure inside the sealed section 808. If the pressure is not reduced, heat transfer occurs in the sealed section 808 by convection and conduction heat transfer due to air, and by inter-surface radiative heat transfer in a constant temperature region. By reducing the pressure in the sealed section 808, the effects of convection and conduction heat transfer due to air may be reduced, thereby achieving the desired thermal resistance value. Alternatively, an insulating material that has been sealed by reducing the pressure inside beforehand, such as a vacuum insulating panel, may be used. Both the first thermal resistance sections 8a and 8b may have a structure in which a sealed section 808 is present, or either the first thermal resistance section 8a or 8b may have a structure in which a sealed section 808 is present.

[0036] The thermal resistance values ​​of the first thermal resistance sections 8a and 8b can be easily changed by using the above structure. Even if it becomes necessary to change the set temperature of the constant temperature regions 6a to 6c, by changing the thermal resistance value using the above structure, it is possible to realize constant temperature regions 6a to 6c with different set temperatures in a short study period without significantly changing the overall structure. Each of the first thermal resistance sections 8a and 8b may be composed of one of the above structures, or multiple structures may be combined.

[0037] With the above configuration, in this embodiment, even if the constant temperature unit 6 is divided into multiple regions with different set temperatures, a single temperature control system consisting of the heat transfer unit 7, temperature sensor unit 11, control unit 12, and power supply unit 13 can set the temperatures of the multiple constant temperature regions 6a to 6c to different set temperatures. As a result, in the liquid processing apparatus 4 of this embodiment, since multiple constant temperature regions 6a to 6c with different set temperatures are available, there is no need to wait for the temperature of the constant temperature unit to rise or fall, and the constant temperature regions 6a to 6c with different optimal temperatures depending on the liquid processing can be immediately used, which is expected to improve the throughput of liquid processing. In addition, the control system can be simplified, and a reduction in the cost related to the manufacture of the apparatus can be expected.

[0038] Furthermore, compared to a structure that separates constant temperature regions with different set temperatures and effectively insulates them to be thermally independent, this structure, which adjusts heat transfer between constant temperature regions 6a to 6c via the first thermal resistance sections 8a and 8b, allows for the construction of a smaller overall liquid processing apparatus. This makes it possible to use multi-well plates as liquid containers, which is expected to reduce the man-hours involved in replacing liquid containers and the risk of mix-ups. [Examples]

[0039] One embodiment of the liquid processing apparatus of Example 2 will be described. Figure 7 is a schematic diagram showing the cross-sectional structure of the liquid processing apparatus of Example 2. In this embodiment, a structure in which three constant temperature regions are set to different temperatures by multiple temperature control systems will be described. Elements that overlap with Example 1 will be omitted from explanation as appropriate.

[0040] The heat transfer unit 7 heats or cools the constant temperature unit 6. If the set temperatures of the constant temperature regions 6a to 6c are higher than the ambient temperature, the heat transfer unit 7 can use a heat-generating component such as a heater. If the set temperatures of the constant temperature regions 6a to 6c are lower than the ambient temperature, the heat transfer unit 7 can be cooled by using a Peltier module or the like. In this embodiment, the constant temperature regions 6a, 6b, and 6c, which have different set temperatures, are heated or cooled by the heat transfer units 7a, 7b, and 7c, respectively.

[0041] In this embodiment, temperature sensor units 11a, 11b, and 11c are installed in constant temperature regions 6a, 6b, and 6c, respectively. Each temperature sensor unit 11a, 11b, and 11c measures the temperature of constant temperature region 6a, 6b, and 6c, respectively. The measurement results from the temperature sensor units 11a, 11b, and 11c are input to the control units 12a, 12b, and 12c, respectively. Each of the control units 12a, 12b, and 12c controls the power supplied by the power supply units 13a, 13b, and 13c to the heat transfer units 7a, 7b, and 7c, respectively, so that the temperatures of constant temperature regions 6a, 6b, and 6c reach their respective set temperatures. As described above, in this embodiment, a temperature control system consisting of a heat transfer unit 7a, a temperature sensor unit 11a, a control unit 12a, and a power supply unit 13a is provided for the constant temperature region 6a, a temperature control system consisting of a heat transfer unit 7b, a temperature sensor unit 11b, a control unit 12b, and a power supply unit 13b is provided for the constant temperature region 6b, and a temperature control system consisting of a heat transfer unit 7c, a temperature sensor unit 11c, a control unit 12c, and a power supply unit 13c is provided for the constant temperature region 6c. Alternatively, a single controller having a processor and memory may perform the functions of the control unit 12a, control unit 12b, and control unit 12c.

[0042] As in this embodiment, a structure may be provided in which multiple temperature control systems, each consisting of a heat transfer unit, a temperature sensor unit, a control unit, and a power supply unit, are provided for each of the multiple constant temperature regions 6a to 6c with different set temperatures. In this embodiment, a structure is shown in which the same number of temperature control systems are provided for the three constant temperature regions 6a to 6c with different set temperatures. The configuration is not limited to this, and the number of temperature control systems may be one or more, and less than the number of constant temperature regions 6a to 6c with different set temperatures. A structure with one temperature control system corresponds to Embodiment 1.

[0043] With the above configuration, in this embodiment, even if the constant temperature unit 6 is divided into multiple regions with different set temperatures, the temperatures of the multiple constant temperature regions 6a to 6c can be set to different set temperatures by multiple temperature control systems. As a result, in the liquid processing apparatus 4 of this embodiment, since multiple constant temperature regions 6a to 6c with different set temperatures are available, there is no need to wait for the temperature of the constant temperature unit to rise or fall, and the constant temperature regions 6a to 6c with different optimal temperatures can be immediately used depending on the liquid processing, which is expected to improve the throughput of liquid processing. Furthermore, if the number of temperature control systems is less than the number of constant temperature regions 6a to 6c with different set temperatures, the control system can be simplified, and a reduction in the cost of manufacturing the apparatus can be expected.

[0044] Furthermore, compared to a structure that separates constant temperature regions with different set temperatures and effectively insulates them to be thermally independent, this structure, which adjusts heat transfer between constant temperature regions 6a to 6c via the first thermal resistance sections 8a and 8b, allows for the construction of a smaller overall liquid processing apparatus. This makes it possible to use multi-well plates as liquid containers, which is expected to reduce the man-hours involved in replacing liquid containers and the risk of mix-ups. [Examples]

[0045] One embodiment of the liquid processing apparatus of Example 3 will be described. Figure 8 is a schematic diagram showing the cross-sectional structure of the liquid processing apparatus of Example 3. In this embodiment, a structure is described in which three constant temperature regions 6a to 6c are each set to different temperatures by a single temperature control system, and a single heat transfer unit heats or cools the multiple constant temperature regions 6a to 6c. Elements that overlap with Example 1 will be omitted from explanation as appropriate. In the example of Figure 8, the temperature sensor unit 11 is installed in constant temperature region 6a, but the temperature sensor unit 11 may also be installed in constant temperature region 6b or constant temperature region 6c.

[0046] The heat transfer unit 7 heats or cools the constant temperature unit 6. If the set temperatures of the constant temperature regions 6a to 6c are higher than the ambient temperature, a heat-generating component such as a heater can be used in the heat transfer unit 7. If the set temperatures of the constant temperature regions 6a to 6c are lower than the ambient temperature, the heat transfer unit 7 can be cooled by using a Peltier module or the like. In this embodiment, there are three constant temperature regions 6a to 6c with different set temperatures, but only one heat transfer unit 7 is needed. The heat transfer unit 7 may also include a heat conductive member to equalize the temperature of the heat transfer unit 7. In this embodiment, the heat transfer unit 7 has a heater 701 and a heat conductive member 702. It is desirable that the heat conductive member 702 be made of a material with high thermal conductivity. For example, it is desirable that it be made of copper, aluminum, or an alloy thereof.

[0047] The second thermal resistance sections 14a to 14c are located between the heat transfer section 7 and the constant temperature section 6, and are pre-equipped with the thermal resistance value necessary for the temperature of the constant temperature regions 6a to 6c to reach the set temperature by adjusting the amount of heat transferred from the heat transfer section 7 to the constant temperature section 6. In this embodiment, the second thermal resistance section 14a adjusts the amount of heat transferred from the heat transfer section 7 to the constant temperature region 6a and has a thermal resistance value such that the constant temperature region 6a reaches the set temperature of 80°C. The second thermal resistance section 14b adjusts the amount of heat transferred from the heat transfer section 7 to the constant temperature region 6b and has a thermal resistance value such that the constant temperature region 6b reaches the set temperature of 70°C. The second thermal resistance section 14c adjusts the amount of heat transferred from the heat transfer section 7 to the constant temperature region 6c and has a thermal resistance value such that the constant temperature region 6c reaches the set temperature of 60°C. The thermal resistance values ​​of the second thermal resistance sections 14a to 14c can be determined using a structure similar to that of the first thermal resistance sections 8a and 8b shown in Figures 4, 5, and 6.

[0048] As an example of the structure of the second thermal resistance section 14a to 14c, a single thermal resistance member may be used to provide the desired thermal resistance value. As the thermal resistance member, for example, a uniform solid material with a lower thermal conductivity than the constant temperature section 6 can be selected and placed. In terms of creating a temperature difference between the constant temperature section 6 and the heat transfer section 7, a solid material with a lower thermal conductivity than the constant temperature section 6 is desirable. Examples of materials that can be used include resin-based materials, rubber-based materials, and insulating materials. In addition to solid materials, a gas layer may also be used as the thermal resistance member.

[0049] As an example of another structure for the second thermal resistance section 14a to 14c, a desired thermal resistance value may be provided by protrusions and recesses provided on the surface of the constant temperature section 6 or the surface of the heat transfer section 7 (heat conductive member 702). When protrusions and recesses are provided on the surface of the constant temperature section 6, the contact area between the protrusions on the surface of the constant temperature section 6 and the surface of the heat transfer section 7 (heat conductive member 702) can be changed to adjust the solid conduction heat transfer by the protrusions and provide a desired thermal resistance value. The recesses may be made of a solid material with an appropriate thermal conductivity, similar to the thermal resistance member, or a gas layer. Alternatively, the constant temperature section 6 and the second thermal resistance section 14a to 14c may be made as a single component, and the structure corresponding to the protrusions and recesses may be created by machining holes. In this case, the contact surface between the constant temperature section 6, which is integrated with the second thermal resistance section 14a to 14c, and the heat transfer section 7 can be made substantially flat, making assembly easier.

[0050] As an example of other structures for the second thermal resistance section 14a to 14c, a desired thermal resistance value may be provided by spacers and fastening members. The spacers and fastening members can not only fix the constant temperature section 6 and the heat transfer section 7 in a predetermined relative position, but can also play a role in adjusting solid conductive heat transfer. As a method of adjusting solid conductive heat transfer with spacers, the heat transfer area may be changed by changing the size of the spacers, the heat transfer area may be changed by changing the number of spacers placed, or spacers may be made of materials with different thermal conductivity. For example, when fastening the spacers with fastening members, resin washers with low thermal conductivity can be used. As a method of adjusting solid conductive heat transfer with fastening members, fastening members may be made of materials with different thermal conductivity. For example, resin screws can be used as fastening members.

[0051] As an example of another structure for the second thermal resistance section 14a to 14c, a desired thermal resistance value may be provided by a thermal radiation section provided on the surface of the constant temperature section 6 or the heat transfer section 7. In this structure, the desired thermal resistance value is achieved by adjusting the radiant heat transfer between the surfaces of the constant temperature section 6 and the heat transfer section 7. A surface treatment that changes the emissivity may be applied to the thermal radiation section. For example, a radioactive paint may be used, or an oxide film such as anodized aluminum may be formed. Alternatively, the desired thermal resistance value may be achieved by adjusting the radiant heat transfer by the area to which the surface treatment is applied.

[0052] As an example of another structure for the second thermal resistance section 14a to 14c, a sealed section may be formed and the internal pressure reduced to achieve the desired thermal resistance value. In the sealed section, if the pressure is not reduced, heat transfer occurs through convection and conduction by air, and through radiative heat transfer between the surfaces of the constant temperature section 6 and the heat transfer section 7. By reducing the pressure in the sealed section, the effects of convection and conduction by air may be reduced to achieve the desired thermal resistance value. Alternatively, an insulating material that has been sealed with the internal pressure reduced beforehand, such as a vacuum insulation panel, may be used.

[0053] With the above configuration, in this embodiment, even if the constant temperature unit 6 is divided into multiple regions with different set temperatures, a single temperature control system consisting of the heat transfer unit 7, temperature sensor unit 11, control unit 12, and power supply unit 13 can set the temperatures of the multiple constant temperature regions 6a to 6c to different set temperatures. As a result, in the liquid processing apparatus 4 of this embodiment, since multiple constant temperature regions 6a to 6c with different set temperatures are available, there is no need to wait for the temperature of the constant temperature unit to rise or fall, and the constant temperature regions 6a to 6c with different optimal temperatures depending on the liquid processing can be immediately used, which is expected to improve the throughput of liquid processing. In addition, the control system can be simplified, and a reduction in the cost related to the manufacture of the apparatus can be expected.

[0054] Furthermore, compared to a structure that separates constant temperature regions with different set temperatures and effectively insulates them to be thermally independent, this structure, which adjusts heat transfer between constant temperature regions 6a to 6c via the first thermal resistance sections 8a and 8b, allows for the construction of a smaller overall liquid processing apparatus. This makes it possible to use multi-well plates as liquid containers, which is expected to reduce the man-hours involved in replacing liquid containers and the risk of mix-ups. [Examples]

[0055] One embodiment of the third thermal resistance section 15a and 15b of the liquid processing apparatus of Example 4 will be described. Figure 9 is a schematic diagram showing the cross-sectional structure of the third thermal resistance section 15a and 15b of Example 4. Constant temperature regions 6a, 6b, and 6c, which have different set temperatures, are separated by the first thermal resistance sections 8a and 8b. If the first thermal resistance sections 8a and 8b are not provided with sufficient thermal resistance for the difference in set temperatures between constant temperature regions 6a, 6b, and 6c, the temperatures of constant temperature regions 6a, 6b, and 6c will deviate from the set temperatures. Even in such a case, in order to bring the temperature of the liquid 1 to the optimal temperature for liquid processing, the third thermal resistance section 15a and 15b can be provided between the liquid container 2 and the container holding section 5 of the constant temperature section 6. The third thermal resistance section 15a is provided between the liquid container 2 and constant temperature region 6b, and the third thermal resistance section 15b is provided between the liquid container 2 and constant temperature region 6c. In the example shown in Figure 9, both the third thermal resistance section 15a and 15b are provided, but either the third thermal resistance section 15a or 15b may be provided. Alternatively, the third thermal resistance section may be provided between the liquid container 2 and the constant temperature region 6a. The third thermal resistance sections 15a and 15b are pre-equipped with the thermal resistance value necessary for the temperature of the liquid 1 to reach a predetermined temperature optimal for liquid processing by adjusting the amount of heat transferred between the constant temperature section 6 and the liquid container 2 when the temperature of the constant temperature section 6 is farther from the ambient temperature than the optimal temperature for liquid processing of the liquid 1. The thermal resistance value of the third thermal resistance sections 15a and 15b can be determined using a structure similar to that of the first thermal resistance sections 8a and 8b shown in Figures 4, 5, and 6.

[0056] As an example of the structure of the third thermal resistance section 15a and 15b, a single thermal resistance member may be used to provide the desired thermal resistance value. As the thermal resistance member, for example, a uniform solid material with a lower thermal conductivity than the constant temperature section 6 can be selected and placed. In terms of creating a temperature difference between the constant temperature section 6 and the liquid 1, a solid material with a lower thermal conductivity than the constant temperature section 6 is desirable. Examples of materials that can be used include resin-based materials, rubber-based materials, and insulating materials. In addition to solid materials, a gas layer may be used as the thermal resistance member.

[0057] As an example of another structure for the third thermal resistance section 15a and 15b, the desired thermal resistance value may be provided by protrusions and recesses on the surface of the constant temperature section 6. When protrusions and recesses are provided on the surface of the constant temperature section 6, the contact area between the protrusions on the surface of the constant temperature section 6 and the surface of the liquid container 2 can be changed to adjust the solid conduction heat transfer by the protrusions and thereby provide the desired thermal resistance value. The recesses may be made of a solid material with appropriate thermal conductivity or a gas layer, similar to the thermal resistance members. Alternatively, the constant temperature section 6 and the third thermal resistance sections 15a and 15b may be made into a single component with holes drilled to create a structure equivalent to the protrusions and recesses.

[0058] As an example of another structure for the third thermal resistance section 15a and 15b, a spacer may be used to provide a desired thermal resistance value. The spacer can fix the constant temperature section 6 and the liquid container 2 in a predetermined relative position, and can also play a role in adjusting solid conductive heat transfer. As a method of adjusting solid conductive heat transfer with spacers, the heat transfer area may be changed by changing the size of the spacer, the heat transfer area may be changed by changing the number of spacers, or spacers may be made of materials with different thermal conductivity.

[0059] As an example of another structure for the third thermal resistance section 15a and 15b, a desired thermal resistance value may be provided by a thermal radiation section provided on the surface of the constant temperature section 6. In this structure, the desired thermal resistance value is obtained by adjusting the radiant heat transfer on the surface of the constant temperature section 6. A surface treatment that changes the emissivity may be applied to the thermal radiation section. For example, a radioactive paint may be used, or an oxide film such as anodized aluminum may be formed. Alternatively, the desired thermal resistance value may be obtained by adjusting the radiant heat transfer by the area to which the surface treatment is applied.

[0060] As an example of another structure for the third thermal resistance section 15a and 15b, a sealed section may be formed and the inside reduced in pressure to achieve a desired thermal resistance value. In the sealed section, if the pressure is not reduced, heat transfer occurs through convection and conduction by air, and through radiant heat transfer between the surfaces of the constant temperature section 6 and the liquid container 2. By reducing the pressure in the sealed section, the effects of convection and conduction by air may be reduced to achieve a desired thermal resistance value. Alternatively, an insulating material that has been sealed with the inside reduced in advance, such as a vacuum insulation panel, may be used.

[0061] With the above configuration, in this embodiment, even if the constant temperature unit 6 is divided into multiple regions with different set temperatures, the temperatures of the multiple constant temperature regions 6a to 6c can be set to different set temperatures by a single temperature control system. As a result, in the liquid processing apparatus 4 of this embodiment, since multiple constant temperature regions 6a to 6c with different set temperatures are available, there is no need to wait for the temperature of the constant temperature unit to rise or fall, and the constant temperature regions 6a to 6c with different optimal temperatures depending on the liquid processing can be immediately utilized, which is expected to improve the throughput of liquid processing. In addition, the control system can be simplified, and a reduction in the cost related to the manufacture of the apparatus can be expected.

[0062] Furthermore, compared to a structure that separates constant temperature sections with different set temperatures and effectively insulates them to be thermally independent, adjusting the heat transfer between constant temperature regions 6a to 6c via the first thermal resistance sections 8a and 8b allows for the construction of a smaller overall liquid processing apparatus. This makes it possible to use multi-well plates as liquid containers, which is expected to reduce the man-hours involved in replacing liquid containers and the risk of mix-ups.

[0063] This disclosure is not limited to the embodiments described above, and includes various modifications. For example, the embodiments described above are described in detail for the purpose of explaining this disclosure clearly, and are not necessarily limited to those having all the configurations described. In addition, it is possible to add, delete, or replace some of the configurations of each embodiment with other configurations.

[0064] For example, in Example 1 there was one heat transfer unit and in Example 2 there were three heat transfer units, but the number of heat transfer units in this disclosure is not limited, and for example, two heat transfer units may be provided for three constant temperature regions. In this case, at least one of the two heat transfer units heats or cools the constant temperature region whose set temperature is furthest from the ambient temperature.

[0065] Furthermore, in Example 3, second thermal resistance sections 14a to 14c were provided in each of the constant temperature regions 6a to 6c. However, the number of second thermal resistance sections in this disclosure is not limited, and second thermal resistance sections may be provided in one or more constant temperature regions selected from the constant temperature regions 6a to 6c.

[0066] Furthermore, as shown in Figure 10, the nucleic acid extraction device 101 is equipped with the liquid processing device 4 of Examples 1 to 4 described above. The gene testing device 110 is equipped with the nucleic acid extraction device 101. Since the nucleic acid extraction device 101 and the gene testing device 110 are equipped with the liquid processing device 4 of Examples 1 to 4 described above, the same effects as described above can be obtained. [Explanation of symbols]

[0067] liquid...1 Liquid container...2 Dispenser...3 Liquid processing equipment...4 Container holding part...5 Constant temperature section...6 Constant temperature range...6a~6c Heat transfer part...7,7a~7c First thermal resistance section...8a,8b Heat dissipation section...9 Insulation section...10 Temperature sensor section...11,11a~11c Control Units: 12, 12a~12c Power supply section...13,13a~13c Second thermal resistance section...14a~14c Third thermal resistance section...15a,15b Nucleic acid extraction device...101 Genetic testing equipment...110 Heater...701 Heat conductive material...702 Thermal resistance component...801 Convex part...802 Recessed section...803 Spacer...804 Fastening component...805 Thermal radiation section...806 Thermal radiation section...807 Sealed part...808

Claims

1. A container holding section is provided for holding a liquid container containing a liquid, and a constant temperature section has multiple constant temperature regions with different set temperatures. A dispensing machine that sucks up or dispenses the liquid contained in the liquid container, A heat transfer unit for heating or cooling the constant temperature unit, A temperature sensor unit that outputs data related to the temperature of the constant temperature unit, A power supply unit that supplies power to the heat transfer section, A control unit controls the power supplied by the power supply unit to the heat transfer unit based on the output of the temperature sensor unit, It comprises a first thermal resistance section that separates at least two of the constant temperature regions, The first thermal resistance portion has a greater thermal resistance value than the constant temperature portion, and has a thermal resistance value such that when the temperature of one constant temperature region separated by the first thermal resistance portion reaches the set temperature of that one constant temperature region, the temperature of another constant temperature region separated by the first thermal resistance portion reaches the set temperature of that other constant temperature region. The heat transfer unit is a single unit, and this heat transfer unit is in contact with the constant temperature region where the set temperature is furthest from the ambient temperature, but not with any other constant temperature regions, thereby heating or cooling the constant temperature region where the set temperature is furthest from the ambient temperature. The aforementioned multiple constant temperature regions are three or more. The temperature sensor unit is positioned only in the constant temperature region other than the constant temperature region where the set temperature is furthest from the ambient temperature and the constant temperature region where the set temperature is closest to the ambient temperature. In this way, it measures the temperature of the constant temperature region other than the constant temperature region where the set temperature is furthest from the ambient temperature and the constant temperature region where the set temperature is closest to the ambient temperature. A liquid processing apparatus characterized by the following:

2. The first thermal resistance section is composed of one of the following, or a combination thereof: a uniform solid material with a lower thermal conductivity than the constant temperature section, a gas layer, a spacer, a fastening member, an uneven structure applied to the surface of the constant temperature section, a radiant treatment applied to the surface of the constant temperature section, or a sealed and depressurized space. The liquid processing apparatus according to claim 1, characterized by its features.

3. The number of heat transfer units is less than the number of constant temperature regions. The liquid processing apparatus according to claim 1.

4. The system further comprises a second thermal resistance section provided in at least two of the aforementioned plurality of constant temperature regions, The heat transfer unit heats or cools the constant temperature region where the second thermal resistance unit is provided via the second thermal resistance unit. Each of the second thermal resistance sections has a thermal resistance value such that when the temperature of the constant temperature region in which one of the second thermal resistance sections is provided reaches the set temperature of that constant temperature region, the temperature of the constant temperature region in which the other second thermal resistance section is provided reaches the set temperature of that constant temperature region. The liquid processing apparatus according to claim 1.

5. At least one of the second thermal resistance sections is composed of a uniform solid material with a lower thermal conductivity than the constant temperature section, a gas layer, a spacer, a fastening member, an uneven surface applied to the constant temperature section or the heat transfer section, a radiant treatment applied to the surface of the constant temperature section or the heat transfer section, a sealed and depressurized space, or a combination thereof. The liquid processing apparatus according to feature 4.

6. The container further comprises a third thermal resistance section provided between the liquid container held by the container holding section and the constant temperature section, The third thermal resistance portion has a thermal resistance value such that when the temperature of a constant temperature region where the third thermal resistance portion is not provided reaches the set temperature of that constant temperature region, the temperature of the liquid processed in the constant temperature region where the third thermal resistance portion is provided reaches a predetermined temperature. The liquid processing apparatus according to claim 1.

7. The third thermal resistance section is composed of one or a combination thereof: a uniform solid material with lower thermal conductivity than the constant temperature section, a gas layer, a spacer, a fastening member, an uneven surface applied to the surface of the constant temperature section, a radiant treatment applied to the surface of the constant temperature section, or a sealed, depressurized space. The liquid processing apparatus according to claim 6.

8. The system further includes a heat dissipation section provided in at least one of the constant temperature regions other than the constant temperature region where the set temperature is furthest from the ambient temperature. The liquid processing apparatus according to claim 1.

9. When performing liquid processing in the plurality of constant temperature regions with different set temperatures, the control unit controls the power supplied to the heat transfer unit based on the data output by the temperature sensor unit so that the constant temperature region where the temperature sensor unit is located reaches the set temperature. The liquid processing apparatus according to claim 1.

10. The liquid processing apparatus comprises the liquid processing apparatus according to any one of claims 1 to 9. A nucleic acid extraction apparatus characterized by the following features.

11. The liquid processing apparatus comprises the liquid processing apparatus according to any one of claims 1 to 9. A gene testing device characterized by the following features.

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