Reactor and stabilizing member
The reaction apparatus addresses condensation issues by using a stabilizing member with a flange and tubular design to maintain reagent concentration and ensure stable reaction outcomes.
Patent Information
- Application Number
- JP2024098188
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-06-18
- Publication Date
- 2026-01-06
AI Technical Summary
Existing reaction apparatuses face issues with condensation inside reagent containers, affecting the reproducibility and quantitativeness of optical measurements.
A reaction apparatus with a reagent container mounting section that includes a support section, cooling section, and a stabilizing member with a flange and tubular portion to reduce condensation, using materials like PP or PE to minimize heat transfer and vapor inflow.
Reduces condensation inside reagent containers, maintaining reagent concentration and preventing dilution, thereby stabilizing reaction results.
Smart Images

Figure 2026000706000001_ABST
Abstract
Description
[Technical Field]
[0001] The present invention relates to a reactor and a stabilizing member. [Background technology]
[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 on a substrate in the form of spots. Using an array plate, it is possible to simultaneously observe the interactions between the many immobilized substances and substances in a specimen. Therefore, using an array plate makes it possible to comprehensively analyze the interactions between the many immobilized substances in the form of spots and many 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 samples. 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 fluorescent light 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 Document 1 discloses an inspection technology that uses a plate having a plurality of spots containing biological substances to perform a reaction step including labeling, and a measurement step in which the labeled pattern is optically acquired. In the reaction step of this technology, reagents such as specimens, labels, and cleaning solutions are supplied and discharged onto the plate using a pipette tip. Patent Document 2 discloses a measurement 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 measurement device is provided with an air blower fan as a means for suppressing condensation on the evaporation prevention sheet during cooling. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] Japanese Patent Publication No. 2023-12426 [Patent Document 2] Japanese Patent Application Laid-Open No. 2008-89571 Summary of the Invention [Problem to be solved by the invention]
[0006] In the technique 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 quantitativeness of optical measurements. 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 prevent condensation from forming 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 forming inside the reagent container, and it is necessary to reduce the possibility of condensation in order to stabilize the quantification of optical measurements.
[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. [Means for solving the problem]
[0008] In order to solve the above problems, a reaction apparatus according to one embodiment of the present disclosure includes: a reagent container mounting section including: 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 placed on the reagent container holder in order to aspirate at least a portion of the reagent stored in the reagent container; The apparatus further includes a reaction vessel mounting section on which a reaction vessel is mounted, the reaction vessel being supplied by the pipetter removed from the reagent vessel and in which a reaction product is produced using the reagent. Moreover, a stabilizing member according to one aspect of the present disclosure includes: a stabilizing member that is placed on a reagent container placing section having a cooling section, and that 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 reservoir portion that is connected to the opening and has a portion that is thermally conductively coupled to the cooling section, a flange portion having an opening with a diameter smaller than that of the opening and abutting against the edge portion; and a tubular portion having a hollow portion that protrudes from the flange portion toward the internal space of the storage portion at a position spaced from the inner peripheral surface of the storage portion and communicates with the opening. [Effects of the Invention]
[0009] According to one aspect of the present disclosure, it is possible to reduce the occurrence of condensation inside a reagent container. [Brief explanation of the drawings]
[0010] [Figure 1] FIG. 1 is a schematic diagram illustrating an example of a configuration of a reaction apparatus according to an embodiment of the present disclosure. [Figure 2] FIG. 2 is a schematic cross-sectional view of an example of a reagent container mounting portion. [Figure 3] FIG. 2 is a cross-sectional view of an example of a reagent container. [Figure 4] 3A and 3B are diagrams illustrating a stabilizing member according to the first embodiment. [Figure 5]10A and 10B are diagrams illustrating a stabilizing member according to a second embodiment. [Figure 6] 10A and 10B are diagrams illustrating a stabilizing member according to a third embodiment. [Figure 7] 10A and 10B are diagrams illustrating a stabilizing member according to a fourth embodiment. [Figure 8] 10A and 10B are diagrams illustrating a stabilizing member according to a fifth embodiment. DETAILED DESCRIPTION OF THE INVENTION
[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 holder 165, a reagent vessel mounting section 200, and a pipetter moving mechanism.
[0013] A reaction vessel 140 capable of storing a reagent is placed on the reaction vessel mounting section 120. The reaction vessel mounting section 120 may be equipped with a shaking mechanism that can shake 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 holder 165. Reagent vessels 300 each holding a reagent are placed on the reagent vessel mounting section 200. When replacing a used pipette tip, the pipette tip may be disposed of in, for example, a waste tip holder (not shown), or in an empty space in the tip holder 165. Reagents envisioned in this embodiment include, for example, a specimen collected from a living organism, an antibody that labels the specimen, an antibody reaction stop agent, a buffer solution, and an observation solution. In practice, it is not necessary for all of these exemplified reagents 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. Note that 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 Figure 2. Figure 2 is a diagram showing a cross section (AA cross section shown in Figure 1) of the reagent container mounting unit 200 illustrated in Figure 1. In the illustration of Figure 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 Figure 2 shows a cross section in this state.
[0016] The reagent container mounting section 200 illustrated here includes a Peltier element 210, a support section 220, a heat insulating section 250, and a protective section 260. The Peltier element 210 is provided in contact with a cooling section 230 constituting the support section 220 to cool the cooling section 230. The support section 220 holds the reagent container 300 vertically below the opening of the reagent container 300 in the supported state, and includes the cooling section 230 that transfers the cooling heat of the Peltier element 210 to the reagent container 300. The illustrated cooling section 230 includes a positioning section 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 section 200, for example, relative to the cooling section 230. That is, the cooling section 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 separated from the cooling unit 230 and provided 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 set 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, it is possible to obtain the effect of making it easier for heat to be transferred to the reagent in the reagent container.
[0019] The heat 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 preventing condensation around the cooling section 230. For example, the heat insulating section 250 may be made of a material having pores, and it is preferable to use an insulating material with a thermal conductivity of 0.034 W / m·K or less. Furthermore, if the heat insulating section 250 is exposed when the reagent container 300 is inserted or removed, the heat insulating section 250 is preferably made of a wipeable closed-cell insulating material, such as PE (polyethylene) foam. In such a case, the heat insulating section 250 may be made of a wipeable closed-cell insulating material only in the exposed portion, 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, for example, ten types of specimens and four reagent containers 300 can be placed thereon. However, the number of specimens and reagent containers 300 is not limited to that shown in the example. The configuration of the reagent container placing section 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 a reagent container. The reagent container 300 used in this embodiment has a conical bottom with a downwardly convex convex shape and a cylindrical top with an open shape. The reagent container 300 is composed of an opening 320, a container edge 340, and a reservoir 360 for storing a reagent. During use, the opening 320 of the reagent container 300 is positioned above in the vertical direction (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. Note that the reagent container 300 is preferably made of a material with high chemical stability, such as PP or PE.
[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 and cause 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 will be described.
[0024] Example 1 The structure of the stabilizing member 400 according to this embodiment will be described below with reference to Fig. 4. Fig. 4(a) is a side view of the stabilizing member 400, and Fig. 4(b) shows the stabilizing member 400 attached to the reagent container 300 and then attached to the reagent container mounting part 200 in the same format as Fig. 2.
[0025] As shown in FIG. 4( a), 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 edge 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 edge 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 reagent stored in the reagent container 300 can be aspirated by the pipette tip 164. That is, as a condition for the reaction apparatus 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 inner 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 due to the reduced diameter of the opening 420 and 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 is 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 region 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 of the reagent container 300 relative to the inner circumferential surface. On the other hand, the insulating effect between the atmosphere in the space above the reagent container mounting unit 200 and the cooling unit 230 is increased by separating the stabilizing member 400, 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 deterioration of the 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 thereof 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 has the effect of preventing condensation on the inner circumferential surface of the tubular portion 430. For this reason, it is preferable that the outer circumferential surface of the tubular portion 430 is as far away as possible from the inner circumferential surface of the reservoir 360. Furthermore, it is preferable that the length of the tubular portion 430 satisfies (1) the relationship of length along the opposing heat insulating portion 250 > length along the cooling portion 230, and (2) a length that ensures that 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 point where it drips, even if condensation occurs on the inner or outer circumferential surface of the tubular section 430.
[0030] Tubular portion 430 may further be provided with a stepped portion 411 having a stepped shape for defining the position of the opening of the stabilizing member, as shown in Fig. 4. 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 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 then measured. As a result, the rate of condensation was reduced to approximately 1%, down from 14% when a conventional stabilizing member was not used. It was also confirmed that the specimen and reagent did not freeze due to overcooling 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 can also 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, in a configuration using such a sheet, the pipette tip must break through the sheet to access the reagent. This raises the risk of improper tip attachment due to the load caused by breaking through the sheet, the adhesion of debris to the tip tip, and the contamination of the reagent with broken pieces of the sheet. By using the stabilizing member 400 according to this embodiment, condensation can be reduced without using such a sheet, and there is no need to consider issues caused by breaking through the sheet.
[0034] Example 2 The stabilizing member 402 according to this embodiment further comprises a heat insulating portion 450 in addition to the stabilizing member 400 described in the first embodiment, thereby further reducing condensation on the tubular portion 430. Details of the stabilizing member 402 will be described below with reference to Fig. 5, which shows the stabilizing member 402 according to this embodiment in a similar format to Fig. 4(b).
[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 way, 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 diluting the reagent concentration due to 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 formed 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] The stabilizing member 403 will be described in detail below with reference to Fig. 6, which shows the stabilizing member 403 according to this embodiment in a similar format to Fig. 4(a). Figs. 6(a) to 6(c) show various embodiments of the retaining portion 460 that retains water generated by condensation on the tubular portion 430 of the stabilizing member 403(a) to (c), respectively.
[0039] In the stabilizing member 403a illustrated in FIG. 6(a), the holding portions 460a are formed as one or more grooves extending circumferentially on 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 portions 460a. The condensed water is prevented from mixing with the reagent by allowing the condensed water to enter the grooves and retaining it by surface tension, and by lengthening the path length that the generated condensed water takes to the lower end surface of the tubular portion 430. Note that the shape and number of the grooves illustrated in FIG. 6(a) are merely examples, and are not limited to the illustrated embodiment as long as the condensed water can be retained in the grooves.
[0040] In the stabilizing member 403b illustrated in FIG. 6(b), the holding portion 460b has a hook-shaped structure provided on the inner periphery of the lower end of the tubular portion 430. Condensed water is held by this hook-shaped portion. In this case, the holding portion 460b can be determined in advance to have a size that functions as a receptacle with a capacity sufficient to hold the amount of condensation that may occur. Note that the shape shown in FIG. 6(b) is only an example, and the holding portion 460b is not limited to a hook shape and can have various sizes and shapes as long as it is large enough to hold a certain amount of condensation.
[0041] In the stabilizing member 403c illustrated in FIG. 6(c), the holding portion 460c is made of an absorbent material disposed at the lower end of the tubular portion 430. Condensed water is absorbed by this absorbent material and thereby held by the holding portion 460c. The absorbent material is preferably made of a material that has the property of absorbing and holding water, such as a water-absorbing sponge or diatomaceous earth. Note that the shape shown in FIG. 6(c) is merely an example, and the position or shape of the holding 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 hold the condensed water.
[0042] The present embodiment exemplified above is realized as the structures exemplified in Figures 6(a) to 6(c). However, this embodiment is not limited to the use of these alone, and multiple of these may be appropriately combined depending on the type of condensation.
[0043] As described above, the stabilizing members 403(a) to (c) 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 generated by the condensation, and thus it is possible to prevent the resulting influence on the reaction results.
[0044] Example 4 When a single reaction is processed in a reactor 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 on 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 embodiment 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 FIG. 4(b), 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 embodiment shown in the figure, 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, it is possible to prevent condensation 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 set the length of the tubular portion 430 long as shown in the figure and to set the length of the tubular portion 430 at a position where 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 will occur on the stabilizing member due to cooling of the stabilizing member via the reagent container 300. In this embodiment, condensation occurring in the tubular portion is suppressed by minimizing the temperature drop of the stabilizing member. Specifically, the flange portion of the stabilizing member 405 is expanded, and a flange portion 413 with a larger contact area with the outside air is used, thereby minimizing the temperature drop of the stabilizing member 405. Details of the stabilizing member 405 will be described below with reference to FIG. 8, which shows the stabilizing member 405 according to this embodiment in a format similar to FIG. 4(b).
[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 placement section 200. In this embodiment, the flange 413 has an extended area, which increases the contact area with the outside air to prevent the stabilizing member 405 from cooling down. 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 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.
[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 invention comprises a reagent container mounting unit 200, a pipette 160, and a reaction container mounting unit 120. The reagent container mounting unit 200 comprises a support unit 220 that supports a reagent container 300 that has an opening 320 positioned vertically upward during use and that stores a predetermined reagent, and a cooling unit 230 that cools a portion of the reagent container 300. The pipette 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 to be supplied by the pipette 160.
[0053] In this reaction apparatus 100, the reagent container mounting unit 200 may have a heat insulating unit 250 that is disposed above the cooling unit 230 and closer to the opening during use, and that thermally inhibits heat absorption by the upper surface of the cooling unit. Such heat insulating unit 250 may be made of a heat 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 disposed above the heat insulating unit 250 and has a member with a higher specific gravity than the aforementioned heat insulating material. Such a protective unit 260 may be chemically stable against hypochlorous acid water or a lower alcohol aqueous solution.
[0054] Furthermore, the support unit 220 can hold the reagent container 300 vertically below the opening 320 of the reagent container 300. Furthermore, the support unit 220 can have a positioning unit 240 that positions the reagent container 300 with respect to the cooling unit 230. Furthermore, the cooling unit 230 can be included in the support unit 220. Note that 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 liquid. That is, the reagent container mounting unit 200 has a plurality of 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 be mounted in distinct and unique locations. In addition, the pipette 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, on container placement section 200-i.
[0055] The present invention 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 from 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 influence 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 heat insulating material (heat insulating unit 250) that is closer to the opening 320 than the region cooled by the cooling unit 230 and that is arranged above the region. The tubular unit 430 described above can be set such that the axial length along the region surrounded by the heat insulating material is longer than the axial length along the cooled region. Furthermore, the tubular unit 430 described above can be set such that the axial length along the heat insulating material is longer than the length of the region of the reagent container 300 surrounded by the heat insulating material.
[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] The present invention includes the following configurations. (Configuration 1) a reagent container mounting section including: 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 placed on the reagent container placement section in order to aspirate at least a portion of the reagent stored in the reagent container; a reaction vessel mounting section on which a reaction vessel is mounted, the reaction vessel being supplied by the pipetter removed from the reagent vessel and in which a reaction product is produced using the reagent; (Configuration 2) The reaction apparatus according to configuration 1, wherein the reagent container mounting section is closer to the opening than the cooling section, is disposed above the cooling section, and has a heat insulating section that thermally inhibits heat absorption by an upper surface of the cooling section. (Configuration 3) 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. (Configuration 4) 4. The reactor according to configuration 3, further comprising a protective section disposed above the heat insulating section and having a member having a higher specific gravity than the heat insulating material. (Configuration 5) 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. (Configuration 6) 6. The reaction apparatus according to any one of configurations 1 to 5, wherein the support part holds the reagent container vertically below the opening. (Configuration 7) 7. The reaction apparatus according to any one of configurations 1 to 6, wherein the support unit has a positioning unit that positions the reagent container with respect to the cooling unit. (Configuration 8) 8. The reactor of claim 6 or 7, wherein the cooling section is included in the support section. (Configuration 9) The reaction apparatus according to any one of configurations 1 to 9, wherein the reagent container mounting section has a plurality of container mounting sections configured to accommodate at least two or more reagents selected from 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 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 the plurality of container mounting sections. (Configuration 10) a stabilizing member that is placed on a reagent container placing section having a cooling section, and that 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 reservoir portion that is connected to the opening and has a portion that is thermally coupled to the cooling section, a flange portion having an opening with a diameter smaller than that of the opening and abutting against the edge portion; a tubular portion having a hollow portion that protrudes from the flange portion toward the internal space of the storage portion at a position spaced from the inner circumferential surface of the storage portion and communicates with the opening; A stabilizing member comprising: (Configuration 11) 11. The stabilizing member of claim 10, configured to reduce the influence of an atmosphere outside the reagent vessel on the atmosphere in the reservoir. (Configuration 12) 12. The stabilizing member according to claim 10, 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. (Configuration 13) 12. The stabilizing member of claim 10 or 11, wherein the tubular portion is spaced apart from an inner circumferential surface of the reservoir when inserted into the opening. (Configuration 14) the reagent container is held by a cooled region and a region surrounded by a thermal insulator, the region being closer to the opening than the cooled region and being disposed above the cooled region; A stabilizing member described in any one of structures 10 to 13, wherein the axial length of the tubular portion along the region surrounded by the insulating material is longer than the axial length along the region to be cooled. (Configuration 15) the reagent container is held by a cooled region and a region surrounded by a thermal insulator, the region being closer to the opening than the cooled region and being disposed above the cooled region; A stabilizing member described in any one of configurations 10 to 13, wherein the axial length of the tubular portion along the insulating material in the axial direction is longer than the length of the region of the reagent container surrounded by the insulating material. (Configuration 16) 16. The stabilizing member according to any one of aspects 10 to 15, 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. (Configuration 17) 17. The stabilizing member of any one of claims 10 to 16, 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. (Configuration 18) 18. The stabilizing member according to any one of aspects 10 to 17, wherein the tubular portion has a holding portion provided on the inner circumferential surface of the hollow portion to hold a liquid.
[0060] It should be noted that the above-described embodiments and examples are merely examples of specific embodiments of the present invention, and the technical scope of the present invention should not be construed as being limited by these. In other words, the present invention can be embodied in various forms without departing from its technical concept or main features. [Explanation of symbols]
[0061] 100: Reactor 120: Reaction vessel mounting section 140: Reaction vessel 160: Pipetta 161: X-axis actuator 162: Y-axis actuator 163: Z-axis actuator 164: Pipette tip 165: Chip storage area 200: Reagent container placement section 200-1 to 200-14: Container placement section 210: Peltier 220: Support part 230: Cooling section 240: Positioning unit 250: Insulation section 260:Protection Department 300: Reagent container 320:Aperture 340: Edge 360: Storage section 400, 402, 403, 404, 405: Stabilizing members 410, 413: Flange part 411: Step 420: Opening 430:Tubular part 440: Hollow part 450: Insulation section 460: Holding part
Claims
1. a reagent container mounting section including: 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 placed on the reagent container holder in order to aspirate at least a portion of the reagent stored in the reagent container; a reaction vessel mounting section on which a reaction vessel is mounted, the reaction vessel being supplied by the pipetter removed from the reagent vessel and in which a reaction product is produced using the reagent;
2. 2. The reaction apparatus according to claim 1, wherein the reagent container mounting section is closer to the opening than the cooling section, is disposed above the cooling section, and has a heat insulating section that thermally inhibits heat absorption by an upper surface of the cooling section.
3. 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. 4. The reactor according to claim 3, further comprising a protective section disposed above the heat insulating section and having a member having a higher specific gravity than the 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 apparatus according to claim 1 , wherein the support part holds the reagent container vertically below the opening.
7. The reaction apparatus 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. 3. The reaction apparatus according to claim 1, wherein the reagent container mounting section has a plurality of container mounting sections configured to accommodate at least two or more reagents selected from 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 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 the plurality of container mounting sections.
10. a stabilizing member that is placed on a reagent container placing section having a cooling section, and that 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 reservoir portion that is connected to the opening and has a portion that is thermally coupled to the cooling section, a flange portion having an opening with a diameter smaller than that of the opening and abutting against the edge portion; a tubular portion having a hollow portion that protrudes from the flange portion toward the internal space of the storage portion at a position spaced from the inner circumferential surface of the storage portion and communicates with the opening.
11. 11. The stabilizing member of claim 10, configured to reduce the influence of an atmosphere outside the reagent vessel on the atmosphere in the reservoir.
12. The stabilizing member according to claim 10 or 11, wherein the tubular portion has a portion that is spaced apart from an inner circumferential surface of the storage portion when inserted into the opening.
13. The stabilizing member according to claim 10 or 11, wherein the tubular portion is spaced apart from an inner circumferential surface of the storage portion when inserted into the opening.
14. the reagent container is held by a cooled region and a region surrounded by a thermal insulator, the region being closer to the opening than the cooled region and being disposed above the cooled region; The stabilizing member according to claim 10 or 11, wherein the axial length of the tubular portion along the region surrounded by the insulating material is longer than the axial length along the region to be cooled.
15. the reagent container is held by a cooled region and a region surrounded by a thermal insulator, the region being closer to the opening than the cooled region and being disposed above the cooled region; The stabilizing member according to claim 10 or 11, wherein the axial length of the tubular portion along the heat insulating material is longer than the length of a region of the reagent container surrounded by the heat insulating material.
16. 12. The stabilizing member according to claim 10, 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. The 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. The stabilizing member according to claim 10 or 11, wherein the tubular portion has a holding portion provided on an inner circumferential surface of the hollow portion to hold a liquid.
Citation Information
Patent Citations
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