Reaction device and stabilization member

The reaction apparatus addresses condensation issues in reagent containers by employing a stabilizing member with a flange and tubular design to minimize vapor inflow and heat transfer, ensuring accurate reagent concentration and reliable reaction outcomes.

WO2025263446A1PCT designated stage Publication Date: 2025-12-26CANON KK
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Patent Information

Application Number
PCT/JP2025/021423
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-06-18
Filing Date
2025-06-13
Publication Date
2025-12-26

AI Technical Summary

Technical Problem

Existing reaction apparatuses face issues with condensation inside reagent containers, which affect the reproducibility and quantitative accuracy of optical measurements due to dilution, as seen in Patent Documents 1 and 2.

Method used

A reaction apparatus with a reagent container mounting section that includes a support section, cooling section, and a stabilizing member with a flange portion and tubular portion to reduce condensation, using materials like PP or PE for the stabilizing member to minimize heat transfer and vapor inflow.

Benefits of technology

The solution effectively reduces condensation inside reagent containers, maintaining reagent concentration and preventing dilution, thereby stabilizing reaction results without the drawbacks of using evaporation prevention sheets.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present disclosure reduces the occurrence of condensation inside a reagent container. In the present disclosure, a reaction device comprises: a reagent container placement part having a support part that supports a reagent container in which a reagent is stored, the reagent container having an edge portion defining an opening and a storage section communicating with the opening, and the reagent container placement part also having a cooling unit that cools at least a portion of the reagent container; a pipettor inserted into and removed from the reagent container placed on the reagent container placement part in order to suction at least a portion of the reagent stored in the reagent container; and a reaction container placement part on which is placed a reaction container that is supplied by the pipettor removed from the reagent container and in which a reaction product is generated using the reagent.
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Description

Reactor and stabilizing member

[0001] The present disclosure relates to a reactor and a stabilizing member.

[0002] Array plates such as protein arrays, peptide arrays, and DNA arrays are known, in which a large number of substances such as proteins, peptides, and nucleic acids are immobilized in the form of spots on a substrate. By using an array plate, it is possible to simultaneously observe the interactions between the large number of immobilized substances and substances in a specimen. Therefore, by using an array plate, it is possible to comprehensively analyze the interactions between the large number of substances immobilized in the form of spots and a large number of substances, including biological specimens such as blood, cell extracts, saliva, and interstitial fluid.

[0003] A known measurement method using an array plate involves selectively fluorescently labeling spots where an interaction of interest has occurred to obtain optical information. A confocal laser microscope is known as a device for observing fluorescently labeled specimens. A confocal laser microscope has an illumination optical system, a fluorescence detection optical system, and a two-dimensional scanning system. The fluorescence detection optical system has the function of detecting the amount of fluorescence from spots labeled with fluorescent probes. The two-dimensional scanning system has the function of acquiring a fluorescent image of the spot area on the array plate by two-dimensionally scanning the array plate or the optical system.

[0004] Patent Literature 1 discloses an inspection technology that uses a plate having multiple spots containing biological substances to perform a reaction process including labeling, followed by a measurement process in which the labeled pattern is optically acquired. In this technology, during the reaction process, reagents such as specimens, labels, and cleaning solutions are supplied and discharged onto the plate using a pipette tip. Patent Literature 2 discloses a measuring device equipped with a cooling unit that is provided with a sheet that prevents evaporation from the reagent plate holding the reagents, enabling multiple reagents to be kept cold. It is disclosed that this measuring device is provided with a blower fan as a means for suppressing condensation on the evaporation prevention sheet during cooling.

[0005] In the technology disclosed in Patent Document 1, there is a concern that the reproducibility of the reaction results may be affected by dilution due to condensed water, which may reduce the quantitative accuracy of optical measurement. In the measuring device disclosed in Patent Document 2, an insulating member is placed on the top surface of the cooling unit to provide efficient cooling, and a blower fan is used to suppress condensation on the top surface of the sheet. However, even in the measuring device disclosed in Patent Document 2, there is still a possibility of condensation occurring inside the reagent container, and reducing the possibility of condensation is required to stabilize the quantification of optical measurement.

[0006] JP 2023-12426 A JP 2008-89571 A

[0007] The present disclosure has been made in consideration of the above circumstances, and one of its objects is to provide a reaction apparatus and a stabilizing member that reduce the occurrence of condensation inside reagent containers.

[0008] In order to solve the above problems, a reaction apparatus according to one aspect of the present disclosure comprises: a reagent container mounting section having a support section for supporting a reagent container in which a reagent is stored, the support section having an edge section that defines an opening and a storage section that communicates with the opening, and a cooling section that cools at least a portion of the reagent container; a pipette that is inserted into and removed from the reagent container mounted on the reagent container mounting section in order to aspirate at least a portion of the reagent stored in the reagent container; and a reaction container mounting section on which a reaction container is mounted, in which a reaction product is produced using the reagent supplied by the pipette that has been removed from the reagent container. Furthermore, a stabilizing member according to one aspect of the present disclosure is a stabilizing member that is placed on a reagent container placing section having a cooling section, and is connected to a reagent container in which a reagent is stored, the stabilizing member having an opening defined by an edge portion and a tubular storage section that is continuous with the opening and has a portion that is thermally coupled to the cooling section, and the stabilizing member comprises: a flange portion that is provided with an opening of a smaller diameter than the opening and abuts the edge portion; and a tubular portion that has a hollow portion that protrudes from the flange portion toward the internal space of the storage section at a position spaced from the inner circumferential surface of the storage section and that communicates with the opening.

[0009] According to one aspect of the present disclosure, it is possible to reduce the occurrence of condensation inside a reagent container.

[0010] FIG. 1 is a schematic diagram showing an example of the configuration of a reaction apparatus according to an embodiment of the present disclosure. FIG. 2 is a cross-sectional schematic diagram of an example of a reagent container mounting unit. FIG. 3 is a diagram showing a cross-section of an example of a reagent container. FIG. 4 is a side view illustrating a stabilizing member of Example 1. FIG. 5 is a schematic diagram showing a state in which a stabilizing member is attached to a reagent container and then attached to the reagent container mounting unit. FIG. 6 is a diagram illustrating a stabilizing member of Example 2. FIG. 7 is a cross-sectional view illustrating the shape of an example of a stabilizing member of Example 3. FIG. 8 is a cross-sectional view illustrating the shape of another example of the stabilizing member of Example 3. FIG. 9 is a cross-sectional view illustrating the shape of another example of the stabilizing member of Example 3. FIG. 10 is a diagram illustrating a stabilizing member of Example 4. FIG. 11 is a diagram illustrating a stabilizing member of Example 5.

[0011] Preferred embodiments and examples will be described in detail below with reference to the drawings. In the following description, common components across multiple drawings are designated by common reference numerals. Therefore, the common components will be described with mutual reference to multiple drawings, and descriptions of components designated by common reference numerals will be omitted as appropriate. Furthermore, the dimensions, materials, shapes, and relative positions of components illustrated in the following embodiments and examples are arbitrary and can be changed depending on the configuration of the device to which the present disclosure is applied or various conditions.

[0012] An example of a reaction apparatus according to an embodiment of the present disclosure will be described below with reference to Fig. 1. Fig. 1 is a diagram showing a schematic configuration of a reaction apparatus 100 according to this embodiment as viewed from above. The reaction apparatus 100 shown in Fig. 1 includes a reaction vessel mounting section 120, a tip storage area 165, a reagent vessel mounting section 200, and a pipetter moving mechanism.

[0013] A reaction vessel 140 capable of storing a reagent is mounted on the reaction vessel mounting section 120. The reaction vessel mounting section 120 may include a shaking mechanism for shaking the reaction vessel 140 to promote the reaction, or a temperature control block for controlling the temperature inside the reaction vessel 140 (not shown). Replacement pipette tips 164 are held in the tip storage area 165. Reagent vessels 300 each holding a reagent are mounted on the reagent vessel mounting section 200. When replacing a used pipette tip, the pipette tip may be disposed of in a waste tip storage area (not shown), or in an empty space in the tip storage area 165. Reagents envisioned in this embodiment include, for example, a specimen collected from a living organism, an antibody for labeling the specimen, an antibody reaction quenching agent, a buffer solution, and an observation solution. In practice, it is not necessary for all of these examples to be used in a single reaction device; at least any of these may be used as a reagent.

[0014] The pipetter movement mechanism includes a holder that holds the pipetter 160 and stage mechanisms 161, 162, and 163 that move the pipetter 160 together with the holder in each of the three X, Y, and Z axes. The pipetter movement mechanism is used to attach a pipette tip 164 to the pipetter 160 and move the pipetter 160 within the device when supplying a reagent from a reagent container 300 in the reagent container mounting unit 200 to a reaction container 140. The pipetter 160 aspirates at least a portion of the reagent stored in the reagent container 300 and, in that state, is moved above the target reaction container 140. The pipetter movement mechanism can use known actuators and control systems as stage mechanisms for X, Y, and Z movement (X-axis actuator 161, Y-axis actuator 162, and Z-axis actuator 163).

[0015] Next, the configuration of the reagent container mounting unit 200 and an example of the reagent container 300 and stabilizing member 400 will be described with reference to FIG. 2. FIG. 2 is a diagram showing a cross section (A-A cross section shown in FIG. 1) of the reagent container mounting unit 200 illustrated in FIG. 1. In the illustration of FIG. 2, for the sake of explanation, the top of the paper corresponds to the top in the Z direction, and the bottom of the paper corresponds to the bottom in the Z direction. The reaction device 100 is used in an arrangement in which the Z direction corresponds to the so-called vertical direction, and the XY plane approximately corresponds to the horizontal plane. Therefore, when the reagent container 300 is supported by the reagent container mounting unit 200, an opening 320 (described later) opens vertically upward, and FIG. 2 shows a cross section in this state.

[0016] The illustrated reagent container mounting unit 200 includes a Peltier element 210, a support unit 220, a heat insulating unit 250, and a protective unit 260. The Peltier element 210 is provided in contact with a cooling unit 230 constituting the support unit 220 to cool the cooling unit 230. The support unit 220 holds the reagent container 300 vertically below the opening of the reagent container 300 in the supported state, and includes the cooling unit 230 that transfers the cooling heat of the Peltier element 210 to the reagent container 300. The illustrated cooling unit 230 includes a positioning unit 240 that has a hole shape to receive the reagent container 300 (described in detail later) and that positions and holds the reagent container 300 at a predetermined height in the Z direction on the reagent container mounting unit 200, for example, relative to the cooling unit 230. That is, the cooling unit 230 holds the reagent container 300 by its outer surface and cools the reagent through the wall of the reagent container 300. Although FIG. 2 illustrates a configuration in which the positioning unit 240 is provided in the cooling unit 230, the positioning unit 240 may be provided separately from the cooling unit 230 and independently.

[0017] The heat insulating section 250 is provided to cover the periphery of the cooling section 230 and insulates heat from the surrounding environment so as to inhibit heat transfer from the surrounding environment to the cooling section 230, specifically, heat absorption from the top surface or side surface of the cooling section 230. In this embodiment, the heat insulating section 250 is provided so as to be positioned closer to the opening 320 of the reagent container 300 in a supported state than the cooling section 230. More specifically, in the illustrated configuration, the heat insulating section 250 is provided so as to face at least a portion of the side surface of a tubular section (described later) across the wall surface of the reagent container 300. The protective section 260 is provided to cover the periphery of the heat insulating section 250 and protects the heat insulating section 250. A stabilizing member 400 that prevents condensation inside the reagent container will be described later.

[0018] The positioning unit 240 holds the reagent container 300 at a position lower than the opening of the reagent container 300, and is configured so that the liquid level of the reagent to be cooled is located below the upper surface of the cooling unit 230. The cooling unit 230 is preferably made of a material with high thermal conductivity, such as aluminum. Furthermore, by matching the shape of the support unit 220 that supports the reagent container 300 to the shape of the reagent container 300, heat can be more easily transferred to the reagent in the reagent container.

[0019] The insulating section 250 is provided for the purposes of insulating against heat from the surrounding environment to improve the cooling performance of the cooling section 230 and to prevent condensation around the cooling section 230. For example, the insulating section 250 may be made of a material having air bubbles, preferably an insulating material with a thermal conductivity of 0.034 W / m·K or less. Furthermore, if the insulating section 250 is exposed when the reagent container 300 is inserted or removed, the insulating section 250 is preferably made of a wipeable closed-cell insulating material, such as PE (polyethylene) foam. In such a case, only the exposed portion of the insulating section 250 may be made of a wipeable closed-cell insulating material, with the remaining portion made of a different insulating material.

[0020] Protective section 260 protects insulating section 250, and is preferably made of a material having a higher specific gravity (lower bulk density) than the insulating material used in insulating section 250. Protective section 260 is also preferably made of a material that can be disinfected with sodium hypochlorite (hypochlorous acid water), ethanol (lower alcohol aqueous solution), or the like. Therefore, protective section 260 is preferably made of a member made of, for example, PP (polypropylene) or PE (polyethylene), which have high chemical stability.

[0021] 1 can accommodate, for example, ten types of specimens and four reagent containers 300. However, the number of specimens and reagent containers 300 is not limited to that shown in the example. The configuration of the reagent container mounting unit 200 is also not limited to that shown in the example. For example, a room temperature reagent unit (not shown in the figure) may be separately provided for reagents that are recommended to be stored at room temperature.

[0022] Next, a reagent container 300 used in this embodiment will be described with reference to FIG. 3 . FIG. 3 is a diagram showing a cross section of the reagent container. The reagent container 300 used in this embodiment has a conical bottom with a downwardly convex cone shape and an open cylindrical top. The reagent container 300 comprises an opening 320, a container edge 340, and a reservoir 360 for storing the reagent. During use, the opening 320 of the reagent container 300 is positioned vertically upward (in the Z-axis direction), and the reservoir 360 communicates with the opening 320 and stores the above-mentioned reagent below in the vertical direction. During use, the reservoir 360 and its vicinity are cooled by the cooling unit 230. It is preferable to use a material such as PP or PE, which has high chemical stability, for the reagent container 300.

[0023] In the reagent container mounting section 200, the occurrence of condensation within the reagent container mounting section 200 can be reduced by covering the cooling section 230 with the insulating section 250. However, as described with reference to FIG. 3 , the reagent container 300 has an opening 320, and the inner circumferential surface of the reservoir 360 is exposed to the atmosphere inside the reaction device 100 without an insulating member. Therefore, warm air containing water vapor may flow into the reagent container 300, causing condensation on the inner circumferential surface of the cooled reservoir 360. Such condensation on the inner circumferential surface of the reagent container 300 may reduce the reagent concentration if it flows into the reagent, and therefore, reduction of this condensation is desired. In the following example, the structure of a stabilizing member 400 intended to reduce such condensation is described.

[0024] 4A and 4B, the structure of the stabilizing member 400 according to this embodiment will be described. Fig. 4A is a side view of the stabilizing member 400, and Fig. 4B shows the stabilizing member 400 attached to the reagent container 300 and then attached to the reagent container mounting portion 200 in a manner similar to that shown in Fig. 2.

[0025] 4A , the stabilizing member 400 according to this embodiment includes a flange portion 410 and a tubular portion 430 that is continuous with the flange portion 410 at one end. The flange portion 410 has an opening 420 that has a smaller diameter than the opening 320 of the reagent container 300 and communicates with a hollow portion 440 that extends in the axial direction of the tubular portion 430 and opens at the other end of the tubular portion 430. The flange portion 410 has an outer diameter and shape that are capable of closing the opening 320 and is configured to abut against the rim portion 340 to close the opening 320. Therefore, by inserting the tubular portion 430 into the opening 320 of the reagent container 300 and attaching the stabilizing member 400 to the reagent container 300 so that the flange portion 410 abuts against the rim portion 340, it is possible to reduce the inflow of air containing water vapor into the reagent container 300. Furthermore, the opening 420 has a diameter larger than the outer diameter of the pipette tip 164 so that the pipette tip 164 can aspirate the reagent stored in the reagent container 300. In other words, as a condition for the reaction device 100 to be able to use the stabilizing member 400, the pipette 160 must be able to use a pipette tip 164 that is large enough to pass through the opening 420.

[0026] The tubular portion 430 has an outer diameter that allows it to be inserted into the opening 320 of the reagent container 300 and maintain a predetermined distance from the inner circumferential surface of the reservoir 360 when inserted into the opening 320. When the stabilizing member 400 is attached to the reagent container 300, the tubular portion 430 protrudes from the flange portion 410 toward the internal space of the reservoir 360 at a position spaced apart from the inner circumferential surface of the reservoir 360. The stabilizing member 400 can further reduce the inflow of air containing water vapor into the inner circumferential surface of the reservoir 360 by reducing the diameter of the opening 420 and by the presence of the tubular portion 430. This reduces the effect of the atmosphere outside the reagent container 300 (such as the air inside the reaction apparatus 100) on the atmosphere inside the reservoir 360.

[0027] Note that, from the viewpoint of reducing the cooling effect of the reagent container 300, it is preferable that the tubular portion 430 be positioned entirely away from the inner circumferential surface of the reservoir 360. However, in the reaction device 100, it is also necessary to insert the pipette tip 164 into the reagent container 300 through the opening reduced in size by the opening 420 to stably aspirate the reagent. From this viewpoint, it is preferable that the stabilizing member 400 is accurately positioned with respect to the reagent container 300 positioned by the positioning unit 240. If this viewpoint is emphasized, for example, the region where the tubular portion 430 is spaced from the inner circumferential surface of the reservoir 360 may be the region corresponding to the cooling unit 230, and part of the region corresponding to the heat insulating unit 250 may be an extension of the stepped portion 411 to improve the positioning accuracy of the stabilizing member 400. The stepped portion 411 is configured to abut against the inner circumferential surface of the reagent container 300 at multiple locations in the circumferential direction. Such multiple abutment locations may be continuous annularly or discretely in the circumferential direction. The thicker the step 411 in the thickness direction of the flange 410 and the narrower the gap between the step 411 and the inner circumferential surface, the more accurate the positioning relative to the inner circumferential surface of the reagent container 300. On the other hand, by separating the stabilizing member 400, the insulating effect between the atmosphere in the space above the reagent container mounting unit 200 and the cooling unit 230 is increased, and the narrower the gap between the step 411 and the inner circumferential surface, the more the insulating effect is reduced. A configuration may be adopted in which a portion spaced from the step 411 in the axial direction of the tubular portion 430 protrudes toward the inner circumferential surface of the reagent container 300 to reduce the reduction in insulating properties. Alternatively, instead of the step 411, a peripheral step (not shown) that contacts the outer circumferential surface of the reagent container 300 may protrude from the flange in the axial direction of the tubular portion 430. The axial direction of the tubular portion 430, the thickness direction of the flange portion 410, and the thickness direction of the step portion 411 are all the same direction.

[0028] Furthermore, the tubular portion 430 has an outer circumferential surface that is positioned at a distance from the inner circumferential surface of the reservoir 360. This reduces the amount of heat transferred from the cooling portion 230 to the stabilizing member 400, and also prevents condensation on the inner circumferential surface of the tubular portion 430. Therefore, it is preferable that the outer circumferential surface of the tubular portion 430 is as far away from the inner circumferential surface of the reservoir 360 as possible. Furthermore, it is preferable that the length of the tubular portion 430 satisfies the following conditions: (1) the length along the opposing heat insulating portion 250 is greater than the length along the cooling portion 230, and (2) the length at which the lower surface of the tubular portion 430 does not come into contact with the reagent liquid surface.

[0029] The reagent container 300 is held on the reagent container mounting section 200 by a region cooled by the cooling section 230 and a region surrounded by the insulating section 250, which is located above the region and closer to the opening 320 than the region cooled by the cooling section 230. In accordance with the above conditions, it is preferable that the axial length of the tubular section 430 along the region surrounded by the insulating section 250 is longer than the axial length along the region to be cooled. Alternatively, it is preferable that the axial length of the tubular section 430 along the insulating section 250 is longer than the axial length of the region surrounded by the insulating section 250. Setting the length of the tubular section 430 as in (1) can reduce the amount of heat transfer from the cooling section 230, and setting it as in (2) can prevent moisture from being supplied to the reagent until the amount reaches a dripping amount, even if condensation occurs on the inner or outer circumferential surface of the tubular section 430.

[0030] Tubular portion 430 may further include a stepped portion 411 having a stepped shape for defining the position of the opening of the stabilizing member, as shown in Figures 4A and 4B. By providing stepped portion 411, the positional relationship between opening 320 and opening 420 can be accurately defined, allowing pipette tip 164 to be brought closer to the reagent more safely. Tubular portion 430 is preferably made of a material that is resistant to cooling by heat transfer from cooling portion 230, and is preferably made of, for example, PP or PE, which has a specific heat capacity in the range of 1.7 to 2.3 kg·K.

[0031] Using the stabilizing member 400 described above, 3.5 ml of reagent liquid was placed in a 50 ml reagent container 300 at an installation environment temperature of 26°C and an installation environment humidity of 80% RH. The rate of condensation (= condensation amount / reagent liquid volume) that occurred when the reagent was cooled for 4.5 hours on the reagent container mounting section 200 was measured. As a result, the rate of condensation was reduced from 14% when a conventional stabilizing member was not used to approximately 1%. It was also confirmed that the specimen and reagent did not freeze due to supercooling at an installation environment temperature of 18°C.

[0032] As described above, the reaction device 100 according to this embodiment and the stabilizing member 400 according to this example can reduce the occurrence of condensation inside the reagent container 300. In addition, it is possible to reduce the possibility of diluting the reagent concentration due to moisture generated by condensation, thereby preventing the resulting influence on the reaction result.

[0033] Furthermore, the measuring device disclosed in Patent Document 2 places a sheet on the top surface of a reagent container to suppress evaporation of the reagent from the reagent container. By providing this sheet, air is prevented from entering the reagent container, thereby reducing condensation on the inner walls of the reagent container. However, when using such a sheet, the pipette tip must break through the sheet to access the reagent. This can lead to improper tip attachment due to the load caused by breaking through the sheet, the adhesion of debris to the tip tip, and the risk of fragments of the sheet becoming mixed into the reagent. By using the stabilizing member 400 according to this embodiment, condensation can be reduced without using such a sheet, eliminating the need to consider issues associated with breaking through the sheet.

[0034] Example 2 A stabilizing member 402 according to this example further includes a heat insulating portion 450 in addition to the stabilizing member 400 described in Example 1, thereby further reducing condensation on the tubular portion 430. Details of the stabilizing member 402 will be described below with reference to Figure 5, which shows the stabilizing member 402 according to this example in a similar format to Figure 4B.

[0035] In the structure described in Example 1, heat from the cooling unit 230 may be transferred to the stabilizing member 400 through the reagent container 300, potentially lowering the temperature of the stabilizing member 400. For this reason, the stabilizing member 402 according to this example is provided with an insulating unit 450 disposed between the opening 320 of the reagent container 300 and the flange 410. In this manner, the rim 340 of the reagent container abuts against the flange 410 via the insulating unit 450, thereby reducing the possibility of the stabilizing member 402 itself being cooled and suppressing condensation. The insulating unit 450 is preferably made of ceramic, a material containing bubbles, or the like.

[0036] As described above, the stabilizing member 402 according to this embodiment can further reduce the occurrence of condensation on the inner circumferential surface of the reagent container 300. Furthermore, it can reduce the possibility of the reagent concentration being diluted by moisture generated by condensation, thereby preventing the resulting influence on the reaction results.

[0037] Example 3 In the stabilizing member 400 described in Example 1, warm air containing water vapor first comes into contact with the inner circumferential surface of the tubular portion 430 when it flows into the reagent container 300. Therefore, when the stabilizing member 400 is cooled to a certain extent, condensation may occur on the inner circumferential surface of the tubular portion 430. The stabilizing member 403 according to this example has a structure that retains condensation that occurs on the tubular portion 430 even if such condensation occurs, thereby reducing the possibility of dilution of the reagent due to moisture caused by condensation.

[0038] 6A to 6C, which show stabilizing member 403 according to this embodiment in a similar manner to that shown in FIG. 4A, the details of stabilizing member 403 will be described below. Figures 6A to 6C show various aspects of retaining portion 460 for retaining water generated by condensation on tubular portion 430 of stabilizing members 403a to 403c, respectively.

[0039] In the stabilizing member 403a illustrated in FIG. 6A , the holding portion 460a is formed as one or more grooves extending circumferentially relative to the inner circumferential surface of the tubular portion 430. Condensed water is retained by allowing it to enter each of the grooves that form the holding portion 460a. The condensed water is prevented from mixing with the reagent by allowing the condensed water to enter the grooves and retaining it through surface tension, and by lengthening the path length of the condensed water leading to the lower end surface of the tubular portion 430. Note that the shape and number of the grooves illustrated in FIG. 6A are merely examples, and are not limited to the illustrated form as long as the condensed water can be retained in the grooves.

[0040] In the stabilizing member 403b illustrated in FIG. 6B , the holding portion 460b has a hook-shaped structure provided on the inner periphery of the lower end of the tubular portion 430. Condensation water is held by this hook-shaped portion. In this case, the holding portion 460b can be determined in advance to determine the amount of condensation that may occur and be sized to function as a receptacle capable of holding that amount. Note that the shape shown in FIG. 6B is only an example, and the holding portion 460b is not limited to a hook-shaped shape and can be of various sizes or shapes as long as it is large enough to hold a certain amount of condensation.

[0041] In the stabilizing member 403c illustrated in FIG. 6C , the retaining portion 460c is formed of an absorbent material disposed at the lower end of the tubular portion 430. Condensed water is absorbed by this absorbent material and thereby retained by the retaining portion 460c. The absorbent material is preferably formed of a material that has the property of absorbing and retaining water, such as a water-absorbing sponge or diatomaceous earth. Note that the shape illustrated in FIG. 6C is merely an example, and the arrangement or shape of the retaining portion 460c may be changed as appropriate depending on, for example, the size of the tubular portion 430, as long as the absorbent material can retain the condensed water.

[0042] The present embodiment exemplified above is realized as the structures illustrated in Figures 6A to 6C. However, this embodiment is not limited to the use of these structures alone, and multiple structures may be combined as appropriate depending on the type of condensation.

[0043] As described above, the stabilizing members 403a to 403c according to this embodiment can reduce the occurrence of condensation inside the reagent container 300 and further reduce the possibility that the condensation will drip onto the reagent. Therefore, it is possible to reduce the possibility that the concentration of the reagent will be diluted by the moisture produced by the condensation, and it is possible to prevent the resulting influence on the reaction results.

[0044] Example 4 When a single reaction is processed in a reaction apparatus capable of processing multiple reactions in parallel, the amount of reagent used is small relative to the capacity of the reagent container 300. In such a reagent container 300, the area of ​​the inner circumferential surface of the reservoir 360 exposed to the air is large, and the amount of condensation that occurs across the entire inner circumferential surface is equal to or greater than that when multiple reactions are processed. Furthermore, since the degree of dilution due to moisture generated by condensation increases when the amount of reagent is small, a structure that further suppresses the occurrence of condensation may be required. This example takes such a situation into consideration and aims to reduce condensation on the inner circumferential surface of the reservoir 360 that is exposed to the air when the amount of reagent is small.

[0045] 7, which shows the stabilizing member 404 according to this embodiment in a similar format to that of FIG. 4B, the details of the stabilizing member 404 will be described below. In the stabilizing member 404 shown in FIG. 7, the length of the tubular portion 430 is set to be longer than the thickness (axial length) of the insulating portion 250 in order to reduce condensation on the inner circumferential surface of the reservoir 360. In the illustrated embodiment, the length of the tubular portion 430 is set so that the end portion extends beyond the area where the insulating portion 250 is located and is positioned near the liquid surface of the reagent stored in the reagent container 300.

[0046] By increasing the length of the tubular portion 430, condensation can be prevented from occurring on the inner circumferential surface of the reservoir 360 from the opening 320 of the reagent container 300 to the height of the lower surface of the tubular portion 430. Therefore, in order to reduce the area where condensation occurs, it is preferable to increase the length of the tubular portion 430 as shown in the figure and set the length of the tubular portion 430 so that it does not come into contact with the reagent liquid surface. In this case, the stabilizing member 404 is cooled more, making condensation more likely to occur. In this embodiment, a structure for retaining condensation, as exemplified in Example 3, may be provided in such a case. Adding such a structure can prevent condensation occurring on the stabilizing member 404 from mixing with the reagent.

[0047] As described above, the stabilizing member 404 according to this embodiment can reduce the occurrence of condensation on the inner circumferential surface of the reservoir 360 when the amount of reagent solution is small. It can also reduce the possibility of diluting the reagent concentration due to moisture generated by condensation, thereby preventing the resulting effect on the reaction results.

[0048] Example 5 When a stabilizing member is used, it is conceivable that condensation may occur on the stabilizing member due to cooling of the stabilizing member via the reagent container 300. In this example, condensation occurring on the tubular portion is suppressed by reducing the temperature drop of the stabilizing member. Specifically, the stabilizing member 405 has an expanded flange portion 413 with a larger contact area with the outside air, thereby reducing the temperature drop of the stabilizing member 405. Details of the stabilizing member 405 will be described below with reference to Figure 8, which shows the stabilizing member 405 according to this example in a format similar to Figure 4B.

[0049] 8 shows a cross section of a reagent container 300 fitted with a stabilizing member 405 having an extended flange 413, placed on the reagent container mounting section 200. In this embodiment, the extended flange 413 is used to increase the contact area with the outside air and suppress cooling of the stabilizing member 405. This reduces the temperature drop of the stabilizing member 405 and reduces condensation on the stabilizing member 405, as in the second embodiment.

[0050] In Example 1, it is stated that PP or PE, which have a specific heat capacity in the range of 1.7 to 2.3 kJ / kg·K, are preferable as the material used for the stabilizing member 400. However, in this example, a material with a relatively high thermal conductivity, such as aluminum, may be used to facilitate the transfer of heat from the outside air taken in by the flange portion 413 to the stabilizing member 405. Furthermore, although not illustrated in the figure, when using multiple stabilizing members in conjunction with multiple reagent containers, the flange portions may be connected together.

[0051] As described above, the stabilizing member 405 according to this embodiment can reduce the occurrence of condensation inside the reagent container 300. It can also further reduce the occurrence of condensation on the stabilizing member 405. This reduces the possibility of the reagent concentration being diluted by moisture generated by the condensation, thereby preventing the resulting influence on the reaction results.

[0052] As described above, the reaction apparatus 100 according to the present disclosure includes a reagent container mounting unit 200, a pipetter 160, and a reaction container mounting unit 120. The reagent container mounting unit 200 includes a support unit 220 that supports a reagent container 300 that has an opening 320 positioned vertically upward during use and stores a predetermined reagent, and a cooling unit 230 that cools a portion of the reagent container 300. The pipetter 160 uses a pipette tip 164 to aspirate at least a portion of the reagent stored in the reagent container 300. The reaction container mounting unit 120 is mounted with a reaction container 140 that stores the reagent supplied by the pipetter 160.

[0053] In this reaction apparatus 100, the reagent container mounting unit 200 may have an insulating unit 250 that is located closer to the opening than the cooling unit 230 and above the cooling unit 230 during use, and that thermally inhibits heat absorption by the upper surface of the cooling unit. Such insulating unit 250 may be made of an insulating material having a thermal conductivity of 0.034 W / m·K or less. The reagent container mounting unit 200 may further include a protective unit 260 that is located above the insulating unit 250 and has a member with a higher specific gravity than the insulating material. Such protective unit 260 may be chemically stable against hypochlorous acid water or a lower alcohol aqueous solution.

[0054] The support unit 220 can hold the reagent container 300 vertically below the opening 320 of the reagent container 300. The support unit 220 can also have a positioning unit 240 that positions the reagent container 300 relative to the cooling unit 230. The cooling unit 230 can also be included in the support unit 220. The above-mentioned reagents can include, for example, at least one of a specimen collected from a living body, an antibody that labels the specimen, an antibody reaction stopping agent, a buffer solution, and an observation solution. That is, the reagent container mounting unit 200 has multiple container mounting units (200-1 to 200-14) so ​​that two or more of these reagents and two or more corresponding reagent containers 300 can each be mounted in a distinct and unique location. In addition, the pipetter 160 is configured to be controlled by a control unit (not shown) to aspirate the desired reagent from a reagent container placed on a selected one of the multiple container placement sections (200-1 to 200-14), for example, container placement section 200-i.

[0055] The present disclosure also includes a stabilizing member (400, 402, 403, 404, 405) for use in the reaction apparatus 100 described above. The stabilizing member has an opening 320 that is positioned vertically upward during use and a reservoir 360 that communicates with the opening 320 and stores a reagent and is positioned vertically downward, and is used with a reagent container 300 in which the reservoir 360 and its vicinity are cooled in the reaction apparatus 100. The stabilizing member includes a flange portion 410 and a tubular portion 430. The flange portion 410 abuts against an edge portion 340 of the reagent container 300 that defines the opening 320 and has an opening 420 that is smaller in diameter than the opening 320. The tubular portion 430 has a side surface that protrudes from the flange portion 410 into the reservoir 360 with a distance from the inner circumferential surface of the reservoir 360, and has a hollow portion 440 that communicates with the reservoir 360 through the opening 420.

[0056] The stabilizing member described above is configured such that the flange portion 410 substantially narrows the opening diameter of the opening 320 to reduce the amount of inflowing air, and the tubular portion 430 prevents the inflowing air from directly reaching the inner wall of the reservoir 360. In other words, the stabilizing member is configured to reduce the effect of the atmosphere outside the reagent container 300 on the atmosphere in the reservoir 360. Note that the tubular portion 430 may have a portion that is spaced apart from the inner circumferential surface of the reservoir 360 when inserted into the opening 320. Alternatively, the tubular portion 430 may be configured to be spaced apart from the inner circumferential surface of the reservoir 360 when inserted into the opening 320.

[0057] In the reaction apparatus 100 described above, the reagent container 300 is held by a region cooled by the cooling unit 230 and a region surrounded by a thermal insulator (thermal insulator 250) that is located above the region and closer to the opening 320 than the region cooled by the cooling unit 230. The axial length of the tubular portion 430 described above along the region surrounded by the thermal insulator can be set to be longer than the axial length of the region cooled. Furthermore, the axial length of the tubular portion 430 described above along the thermal insulator can be set to be longer than the length of the region of the reagent container 300 surrounded by the thermal insulator.

[0058] The tubular portion 430 can be made of a material with a specific heat capacity in the range of 1.7 to 2.3 kJ / kg·K. The stabilizing member can have a heat insulating portion 450 disposed between the rim portion 340 and the flange portion 410 to inhibit heat transfer between the rim portion 340 and the flange portion 410. The tubular portion 430 can also have a holding portion 460 provided on the inner circumferential surface of the hollow portion 440 to hold a liquid. The stabilizing member can also be formed by connecting the flange portions provided on each of a plurality of stabilizing members to form an integrated flange portion.

[0059] It should be noted that the above-described embodiments and examples are merely examples of specific embodiments of the present disclosure, and the technical scope of the present disclosure should not be interpreted as being limited by them. In other words, the present disclosure can be implemented in various forms without departing from its technical concept or main features.

[0060] The present disclosure is not limited to the above-described embodiments, and various modifications and variations are possible without departing from the spirit and scope of the present disclosure. Therefore, the following claims are appended to apprise the public of the scope of the present disclosure.

[0061] This application claims priority based on Japanese Patent Application No. 2024-098188, filed June 18, 2024, the entire contents of which are incorporated herein by reference.

[0062] 100: Reaction apparatus 120: Reaction vessel mounting section 140: Reaction vessel 160: Pipetter 161: X-axis actuator 162: Y-axis actuator 163: Z-axis actuator 164: Pipette tip 165: Tip storage area 200: Reagent vessel mounting section 200-1 to 200-14: Vessel mounting section 210: Peltier element 220: Support section 230: Cooling section 240: Positioning section 250: Heat insulating section 260: Protective section 300: Reagent vessel 320: Opening 340: Edge section 360: Storage section 400, 402, 403, 404, 405: Stabilizing member 410, 413: Flange section 411: Step section 420: Opening 430: Tubular section 440: Hollow section 450: Heat insulating section 460: Holding part

Claims

1. A reaction apparatus comprising: a reagent container mounting section having a support section for supporting a reagent container in which a reagent is stored, the support section having an edge section that defines an opening and a storage section that communicates with the opening, and a cooling section that cools at least a portion of the reagent container; a pipetter that is inserted into and removed from the reagent container mounted on the reagent container mounting section in order to aspirate at least a portion of the reagent stored in the reagent container; and a reaction container mounting section on which a reaction container is mounted in which a reaction product is produced using the reagent supplied by the pipetter that has been removed from the reagent container.

2. The reaction apparatus of claim 1, wherein the reagent container mounting section is closer to the opening than the cooling section, is positioned above the cooling section, and has an insulating section that thermally inhibits heat absorption by the upper surface of the cooling section.

3. The reactor according to claim 2, wherein the heat insulating section includes a heat insulating material having a thermal conductivity of 0.034 W / m·K or less.

4. The reactor according to claim 3, further comprising a protective section disposed above said heat insulating section and having a member having a higher specific gravity than said heat insulating material.

5. The reaction apparatus according to claim 4, wherein the protective part has chemical stability against hypochlorous acid water or a lower alcohol aqueous solution.

6. The reaction device according to claim 1, wherein the support portion holds the reagent container vertically below the opening.

7. The reaction device according to claim 1, wherein the support portion has a positioning portion for positioning the reagent container relative to the cooling portion.

8. The reactor according to claim 6 or 7, wherein the cooling section is included in the support section.

9. A reaction apparatus as described in claim 1 or 2, wherein the reagent container mounting section has a plurality of container mounting sections configured to accommodate at least two or more reagents selected from the group consisting of a specimen collected from a living organism, an antibody that labels the specimen, an antibody reaction stopping agent, a buffer solution, and an observation liquid in two or more corresponding reagent containers, and the pipetter is configured to aspirate the reagent from the reagent container mounted on a container mounting section selectively designated from among the plurality of container mounting sections.

10. A stabilizing member that is placed on a reagent container mounting section having a cooling section, and is connected to a reagent container in which a reagent is stored, the stabilizing member having an opening defined by an edge and a tubular storage section that is continuous with the opening and has a portion that is thermally connected to the cooling section, the stabilizing member comprising: a flange section that is provided with an opening of a smaller diameter than the opening and abuts against the edge; and a tubular section that has a hollow section that protrudes from the flange section toward the internal space of the storage section at a position spaced from the inner surface of the storage section and that communicates with the opening.

11. The stabilizing member of claim 10, configured to reduce the effect of an atmosphere outside the reagent vessel on the atmosphere in the reservoir.

12. A stabilizing member according to claim 10 or 11, wherein the tubular portion has a portion that is spaced apart from the inner circumferential surface of the storage portion when inserted into the opening.

13. A stabilizing member according to claim 10 or 11, wherein the tubular portion is spaced apart from the inner circumferential surface of the reservoir portion when inserted into the opening.

14. A stabilizing member as described in claim 10 or 11, wherein the reagent container is held by a cooled region and a region surrounded by an insulating material that is closer to the opening than the cooled region and is positioned above the cooled region, and the axial length of the tubular portion along the region surrounded by the insulating material is longer than the axial length along the cooled region.

15. A stabilizing member as described in claim 10 or 11, wherein the reagent container is held by a cooled region and a region surrounded by an insulating material that is closer to the opening than the cooled region and is positioned above the cooled region, and the axial length of the tubular portion along the insulating material in the axial direction of the tube is longer than the length of the region of the reagent container surrounded by the insulating material.

16. A stabilizing member according to claim 10 or 11, wherein the tubular portion is made of a material having a specific heat in the range of 1.7 to 2.3 kJ / kg·K.

17. A stabilizing member according to claim 10 or 11, further comprising a heat insulating portion disposed between the edge portion and the flange portion to inhibit heat transfer between the edge portion and the flange portion.

18. A stabilizing member according to claim 10 or 11, wherein the tubular portion has a holding portion provided on the inner circumferential surface of the hollow portion for holding a liquid.

Citation Information

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