Septa
The septum design with protrusions and pre-opened slits addresses manufacturing inefficiencies and defects in conventional septa, reducing costs and improving yield by simplifying the process and ensuring reliable sealing for liquid sample analysis.
Patent Information
- Application Number
- JP2023543519
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-08-24
- Publication Date
- 2025-08-12
- Estimated Expiration
- 2041-08-24
AI Technical Summary
Conventional septa manufacturing processes are costly and inefficient due to the need for cleaning and inspection steps after punching slits, which can lead to defects and reduced yield, and the slits are prone to tearing during processing.
A septum design with cylindrical portions featuring protrusions on the side surfaces and a pre-opened slit configuration, allowing for elastic deformation to facilitate insertion and removal of thin tubes while maintaining a seal, eliminating the need for punching and reducing manufacturing complexity.
The new septum design reduces manufacturing costs and improves yield by simplifying the process, ensuring consistent sealing performance without slit defects, thus enhancing the reliability of liquid sample analysis.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a septum that seals a container such as a well of a microplate or a microtube in a state in which a thin tube such as a capillary or a needle nozzle can be inserted into and removed from the container. [Background technology]
[0002] In fields such as biochemistry and medical diagnosis, electrophoresis is used to analyze DNA, proteins, and other substances. Capillary electrophoresis devices equipped with capillaries are widely used as electrophoresis devices. Capillaries are thin, hollow tubes with an inner layer made of silica or other materials to which charged functional groups are bonded. In capillary electrophoresis devices, liquid samples dispensed into microplates or microtubes are analyzed qualitatively or quantitatively.
[0003] When analyzing a liquid sample, the tip of the capillary is inserted into the liquid sample in a well of a microplate or a microtube. The capillary is used while filled with a migration medium. When a voltage is applied to both ends of the capillary, an electroosmotic flow is formed inside the capillary. Components in the liquid sample are drawn into the capillary by the electroosmotic flow, and as they flow through the capillary, they are separated at migration speeds based on their charge and size. The separated components are optically detected in a detection section downstream in the capillary.
[0004] Generally, capillary electrophoresis instruments are equipped with an autosampler that automatically performs analytical operations such as sampling. The capillaries are fixed inside the instrument so that their tips open downward. When analyzing liquid samples, microplates or microtubes containing the liquid samples are placed on a moving stage. The moving stage is set up so that it can move three-dimensionally relative to the tips of the capillaries.
[0005] The microplate or microtube containing the liquid sample is transported horizontally to below the tip of the capillary by a moving stage, and then raised and lowered vertically relative to the tip of the capillary. When the container rises from below relative to the tip of the capillary, which opens downward, the tip of the capillary is inserted into the well of the microplate or the microtube, allowing the liquid sample to be aspirated.
[0006] Liquid samples placed in containers evaporate and are exposed to airborne particles after preparation and during automated analysis. When the liquid sample is a small volume, on the order of a few hundred μL to 1.5 mL, evaporation of components can significantly affect the analysis results. Furthermore, contamination can occur if airborne particles get mixed in. To prevent such evaporation and contamination problems, containers that hold liquid samples are fitted with septa.
[0007] A septum has the function of sealing a container containing a sample or the like in a manner that allows a thin tube such as a capillary to be inserted and removed. Septa having a structure that seals multiple containers are used in microplates with multiple wells and multi-connected microtubes in which multiple microtubes are connected.
[0008] Generally, a septum is provided as a sheet-like cover made of an elastic elastomer. As shown in Fig. 1, a typical septum includes a sheet-like main body portion as shown by the reference numeral 10, a hole portion as shown by the reference numeral 20, and a cylindrical portion with a bottom as shown by the reference numeral 30. The cylindrical portion is provided so as to elastically fit inside the openings of a plurality of arranged containers, such as a plurality of wells provided on a microplate or a plurality of interconnected microtubes.
[0009] The hole and the cylindrical portion form a through structure that allows a thin tube such as a capillary to pass through into the container. A slit is provided at the bottom of the cylindrical portion. The slit is designed to elastically deform and open when a thin tube such as a capillary is inserted, due to pressure from the thin tube, and to close due to elastic restoring force when the thin tube is removed. The slit, which opens and closes elastically, is designed to allow the thin tube to be inserted into the container while keeping the opening of the container small.
[0010] Patent Documents 1 and 2 describe sample containers and caps with a structure similar to a septum. In Patent Document 1, a slit is provided as a cut (see paragraph 0047). In Patent Document 2, the slit is formed in a cross shape (see paragraph 0039).
[0011] Patent Document 3 describes a septum having a depression in the center and a taper around the depression. Patent Document 3 describes a structure in which, when the taper of the septum comes into contact with the taper of the lid, an external force is applied toward the insertion portion of the cathode end of the capillary, closing the hole (see paragraphs 0055 and 0056). [Prior art documents] [Non-patent literature]
[0012] [Patent Document 1] Japanese Patent Publication No. 2020-160007 [Patent Document 2] Japanese Patent Application Publication No. 2020-160020 [Patent Document 3] International Publication No. 2015 / 037308 Summary of the Invention [Problem to be solved by the invention]
[0013] In a conventional septum, the slit at the bottom of the cylindrical portion is provided as a notch. The notch slit is formed by punching using a thin, straight-blade punch after the cylindrical portion or the like is molded from resin. When a thin tube such as a capillary is inserted into the notch slit, the pressure from the thin tube pushes the inner wall of the slit aside, opening slightly to allow the thin tube to be inserted.
[0014] In a conventional septum, the slit at the bottom of the cylindrical portion is formed as a notch by punching, which poses several problems regarding the septum manufacturing process and the characteristics of the slit.
[0015] In conventional punching processes, the work of attaching the resin-molded septum to a processing jig and transporting the slit-formed septum to the next process must be performed in air. Because punching generates processing waste, it is difficult to manufacture in a clean room. Furthermore, the punch used in processing may have anti-rust oil, rust, etc., attached. If the septum is exposed to air or foreign matter during manufacturing, it may become contaminated. Therefore, a cleaning process is incorporated after punching to clean the septum.
[0016] Furthermore, during conventional punching, individual slits are simultaneously formed in the bottoms of multiple regularly arranged cylindrical portions. This type of processing can result in a small number of slits being improperly punched, misaligned, or dimensionally incorrect. Furthermore, during the cleaning process, the protruding cylindrical portions are prone to being subjected to force, which can cause the edges of the slits to tear. Therefore, after cleaning the septa, a slit inspection process is incorporated in which all septa are inspected for slit dimensions and tears.
[0017] However, incorporating a cleaning process or a slit inspection process into the septum manufacturing process increases the number of steps and equipment costs, resulting in a problem of higher septum manufacturing costs. Furthermore, in manufacturing processes that simultaneously form regularly arranged slits or that clean the septum after slit processing, if even a portion of the slits is defective, the entire septum becomes defective, resulting in a problem of lower yield per product. Patent Documents 1 to 3 do not disclose such cut slits or the problems and solutions associated with cut slits.
[0018] Therefore, an object of the present invention is to provide a septum that can reduce manufacturing costs and improve yields based on the peripheral structure of a slit into which a thin tube such as a capillary is inserted. [Means for solving the problem]
[0019] In order to solve the above problems, the septum according to the present invention comprises a plurality of cylindrical portions that can be fitted inside the openings of a plurality of arranged containers, and a slit formed in the bottom of each of the cylindrical portions, and is configured to assume two states: an inserted state in which a thin tube that sucks or discharges liquid into the container is inserted into the container through the cylindrical portion, and a removed state in which the thin tube is removed from the container to the outside of the cylindrical portion, and when transitioning from the removed state to the inserted state, the septum is slid open by elastic deformation of the cylindrical portion due to pressure from the thin tube. a septum that opens a slit to allow the insertion of the thin tube, and when transitioning from the inserted state to the removed state, closes the slit with the elastic force of the cylindrical portion to seal the container, the cylindrical portion has a protrusion that protrudes radially outward from the side, and the slit is formed in an open shape such that the inner walls of the slit do not abut against each other when the cylindrical portion is removed from the opening, and when the cylindrical portion is fitted inside the opening, the protrusion is pressed by the inner wall of the container, and the protrusion is closed by elastic deformation of the cylindrical portion due to the pressure, sealing the container. The protrusions are positioned so as to sandwich the slit from both outside sides in the short direction of the slit, but not from both outside sides in the long direction of the slit, or the tubular portion has protrusions protruding radially outward from the side, an upper tubular portion formed in a cylindrical shape, and a lower tubular portion formed in a shape in which both radial outsides of a bottomed cylindrical shape are diagonally cut out so as to form a V-shape in side view, and the bottom of the tubular portion is the bottom of the lower tubular portion which has a rectangular shape when viewed from the bottom of the tubular portion. [Effects of the Invention]
[0020] According to the septum of the present invention, the manufacturing cost can be reduced and the yield can be improved based on the peripheral structure of the slit into which a thin tube such as a capillary is inserted. [Brief explanation of the drawings]
[0021] [Figure 1] FIG. 1 is a perspective view showing a septum and a microplate according to an embodiment of the present invention. [Figure 2] FIG. 1 is a cross-sectional view showing a state in which a septum according to an embodiment of the present invention is attached to a microplate. [Figure 3] FIG. 1 is a cross-sectional view showing the structure of a conventional general septum. [Figure 4] FIG. 1 is a perspective view of a cylindrical portion of a conventional general septum, viewed from below. [Figure 5] FIG. 2 is a cross-sectional view showing the structure of a septum according to the present embodiment. [Figure 6] FIG. 2 is a perspective view of the cylindrical portion of the septum according to the embodiment, as viewed from below. [Figure 7A] 1 is a cross-sectional view showing a method (initial state) for sealing a container with a septum according to an embodiment of the present invention. [Figure 7B] 3A to 3C are cross-sectional views showing a method (intermediate state) of sealing a container with a septa according to an embodiment of the present invention. [Figure 7C] 1 is a cross-sectional view showing a method of sealing a container with a septum according to an embodiment of the present invention (sealed state). [Figure 8A] FIG. 10 is a bottom view of the cylindrical portion of the septum, showing an example of the shape of the slit (rectangular). [Figure 8B] FIG. 10 is a bottom view of the cylindrical portion of the septum, showing an example of the shape of the slit (elliptical shape). [Figure 8C] FIG. 10 is a bottom view of the cylindrical portion of the septum, showing an example of the shape of the slit (oval shape). [Figure 8D] FIG. 10 is a bottom view of the cylindrical portion of the septum showing an example of the shape of the slit (diamond shape). [Figure 8E]FIG. 10 is a bottom view of the cylindrical portion of the septum, showing an example of the shape of the slit (mouth shape). [Figure 8F] FIG. 10 is a bottom view of the cylindrical portion of the septum, showing an example of the shape of the slit (spear-shaped). [Figure 9A] FIG. 10 is a perspective view of the cylindrical portion of the septum, showing an example of the shape of the protrusion (rib-like), as viewed from below. [Figure 9B] 10 is a perspective view of the cylindrical portion of the septum, showing an example (auxiliary) of the shape of the protrusion, as viewed from below. FIG. [Figure 9C] FIG. 10 is a perspective view of the cylindrical portion of the septum, showing an example of the shape of the protrusion (wing-like), as viewed from below. [Figure 10] FIG. 1 is a perspective view showing a septum and a multiple microtube according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION
[0022] Hereinafter, a septum according to one embodiment of the present invention will be described with reference to the drawings. Note that common components in the following drawings will be assigned the same reference numerals, and duplicated descriptions will be omitted.
[0023] Fig. 1 is a perspective view showing a septum and a microplate according to an embodiment of the present invention, and Fig. 2 is a cross-sectional view showing a state in which a septum according to an embodiment of the present invention is attached to a microplate. 1 and 2 show a septum 1 for a microplate as an example of a septum according to this embodiment, and a microplate 200 to which the septum 1 is attached.
[0024] The microplate 200 is used as a container in analysis, inspection, experiments, etc. The microplate 200 is made of a highly rigid resin or the like and has a substantially rectangular plate shape. The material of the microplate 200 is polystyrene or a polyolefin such as polypropylene. The microplate 200 is generally made of resin, but may also be made of glass or the like.
[0025] 1, a recess 210 is formed on the top surface of the microplate 200. The recess 210 has a rectangular shape in a plan view of the microplate 200, and is formed over substantially the entire top surface. The recess 210 is surrounded by a thin outer frame 220. The top surface of the microplate 200 is thinned to a substantially uniform thickness, leaving the outer frame 220 around the periphery, thereby forming the dish-shaped recess 210.
[0026] A plurality of wells 230 are formed in the recess 210 of the microplate 200. Each well 230 has a circular shape in a plan view of the microplate 200, and is provided as a tapered, approximately cylindrical depression. The wells 230 are open at the bottom surface of the recess 210. The wells 230 are arranged in a matrix on the bottom surface of the recess 210 at intervals from one another.
[0027] 2, well 230 is composed of a cylindrical upper portion 231 and a cylindrical lower portion 232 with a bottom that tapers downward. A cylindrical space is formed inside upper portion 231. A generally inverted truncated cone-shaped space is formed inside lower portion 232 that tapers downward.
[0028] The internal space of well 230 functions as a container into which a desired liquid or the like is placed. Examples of liquids include liquid samples, solutions in which solid samples are dissolved, dispersions in which solid samples such as powder are dispersed, buffers, standard samples, etc. The liquid to be analyzed dispensed into well 230, the solution or dispersion containing the component to be analyzed, a liquid reactant, a liquid culture, etc., are used for various analyses, tests, experiments, etc.
[0029] 1 and 2, the microplate 200 is a 96-well microplate having a total of 96 wells 230 formed in 8 rows and 12 columns. For example, the wells 230 have a capacity of 100 to 400 μL, an inner diameter of 5 to 8 mm, and a depth of 6 to 20 mm. However, the capacity, inner diameter, outer diameter, depth, and spacing of the wells 230 vary depending on the number of wells in the microplate 200, the well arrangement, etc.
[0030] 1 and 2, recess 210 is provided on the upper surface of microplate 200, and well 230 is provided as a tapered, approximately cylindrical depression, but the shapes of microplate 200 and well 230 are not particularly limited as long as they correspond to septa 1. For example, well 230 may be provided as an approximately cylindrical depression. The bottom of well 230 may be any of a flat bottom, a round bottom, a U-shaped bottom, a V-shaped bottom, etc.
[0031] The microplate 200 can be used as a container for setting samples in an automatic analyzer equipped with an autosampler. Specific examples of automatic analyzers include capillary electrophoresis devices, high performance liquid chromatography (HPLC) devices, and other biochemical analyzers, chemical analyzers, and optical analyzers that perform component analysis, reaction analysis, etc.
[0032] The automatic analyzer includes, as components of an autosampler, a capillary tube that sucks or dispenses liquid into or from a container such as a well 230 of a microplate 200, a microtube, or a microvial, and a moving stage that moves the tip of the capillary tube relative to the well 230 of a microplate 200, a container such as a microtube, or a microvial. The capillary tube is inserted into the container as in nozzle 400 shown in FIG. 4A.
[0033] The capillary tubes for aspirating or discharging liquid are installed in the automatic analyzer so that their tips open downward. The capillary tubes may have only the function of aspirating liquid from containers such as wells 230 of the microplate 200, microtubes, or microvials, or may have only the function of discharging liquid into these containers, or may have both of these functions.
[0034] Specific examples of thin tubes include long, flexible capillaries used in separation operations such as electrophoresis, metal needles that have the function of sucking or discharging liquid, flexible or highly rigid resin nozzles that have the function of sucking or discharging liquid, and metal nozzles that have the function of sucking or discharging liquid.
[0035] The moving stage may move a well 230 of the microplate 200, a microtube, a microvial, or other container relative to the tip of a capillary fixed in the device, or may move the tip of a capillary or the entire capillary relative to a container fixed in the device. The relative movement by the moving stage is performed in the horizontal and vertical directions.
[0036] As shown in Figures 1 and 2, the septum 1 of this embodiment comprises a main body 10 formed in a sheet-like shape, a plurality of hole portions 20 that penetrate the main body 10 from top to bottom, bottomed tubular portions 30 that are formed to protrude downward from around each of the hole portions 20 on the underside of the main body 10, and slits 40 formed in the bottom of each of the tubular portions 30.
[0037] 1 and 2, the septum 1 is provided for a 96-well microplate. The septum 1 for a 96-well microplate has a total of 96 holes 20 and cylindrical portions 30 arranged in 8 rows and 12 columns at positions corresponding to the wells 230 of the microplate 200. In addition, a slit 40 is provided at the bottom of each of the cylindrical portions 30.
[0038] Septa 1 has the function of sealing wells 230 of microplate 200 in a state in which thin tubes such as capillaries, needles, and nozzles 400 (see FIG. 3) of an automatic analyzer can be inserted into and removed from the wells 230. Septa 1 is attached to the upper surface of microplate 200 as shown in FIG. 2 after samples are placed in wells 230 of microplate 200 and before microplate 200 is set in the automatic analyzer.
[0039] The main body 10, hole 20, and cylindrical portion 30 of the septum 1 are integrally resin-molded from an elastic elastomer. Examples of materials for the septum 1 include silicone rubber, fluororubber, and ethylene-propylene-diene rubber (EPDM). The cylindrical portion 30 is designed to have an elastic modulus that allows it to easily elastically deform when pressed into the well 230 or when pressed by the thin tube of an automatic analyzer.
[0040] Methods for resin molding the septa 1 include compression molding and transfer molding. Compression molding is a method in which a resin material is placed in a mold and pressed under heat to form the material. Transfer molding is a method in which a heated resin material is injected into a mold and pressurized to form the material. Compression molding is preferred as a resin molding method because the mold structure is simple and productivity is high.
[0041] 1 and 2, the main body 10 can be sized to be accommodated in the recess 210 of the microplate 200. The length and width of the main body 10 can be smaller than the length and width of the recess 210. The thickness of the main body 10 can be set to be equal to or smaller than the depth of the recess 210.
[0042] By providing such a main body 10, the septum 1 can be easily attached to the recess 210 of the microplate 200 and removed from the recess 210 by utilizing the space around the recess 210. Furthermore, it becomes easy to attach a lid or a retainer above the septum 1 attached to the recess 210 of the microplate 200 as needed.
[0043] Here, the structure of the septum according to this embodiment and the method of sealing a container with the septum according to this embodiment will be described together with the structure of a conventional, general septum and the method of sealing a container with a conventional, general septum.
[0044] Fig. 3 is a cross-sectional view showing the structure of a conventional general septum, and Fig. 4 is a perspective view of the cylindrical portion of a conventional general septum as viewed from below. As shown in Figures 3 and 4, a conventional septum 100 includes a main body 110 formed in a sheet-like shape, a plurality of holes 120 that penetrate the main body 110 from top to bottom, a bottomed tubular portion 130 that is formed to protrude downward from around each of the holes 120 on the underside of the main body 110, and a slit 140 formed in the bottom of each of the tubular portions 130.
[0045] Similar to the septum 1 according to the present embodiment, the conventional septum 100 has the function of sealing the wells 230 of the microplate 200 in a state in which a thin tube such as a capillary, needle, or nozzle of an automatic analyzer can be inserted into and removed from the wells 230. The septum 100 is configured to be attached to the upper surface of the microplate 200.
[0046] In a conventional, typical septum 100, the main body 110, the holes 120, and the cylindrical portion 130 are integrally resin-molded from an elastic elastomer. The holes 120 and the cylindrical portion 130 are arranged in a matrix on the main body 110 at intervals so as to correspond to the wells 230 of the microplate 200. As shown in Fig. 3, the holes 120 and the cylindrical portion 130 form a through structure that passes through the septum 100 from top to bottom.
[0047] The cylindrical portions 130 are provided so as to be able to fit inside the openings of the wells 230 provided on the microplate 200. When the septa 100 is attached to the microplate 200, each cylindrical portion 130 is inserted into each well 230. The outer diameter of the cylindrical portions 130 is set to be equal to or slightly larger than the inner diameter of the wells 230. Furthermore, the cylindrical portions 130 are set so as to be easily elastically deformed by pressure from the inner walls of the wells 230, and are pressed against the inner walls of the wells 230 by their elastic restoring force.
[0048] Therefore, when the cylindrical portion 130 is inserted into the well 230, it is pressed from the inner wall of the opening of the well 230 toward the central axis of the cylindrical portion 130, and is slightly elastically deformed so as to be crushed in the radial direction, and fits into the opening of the well 230. After being inserted into the well 230, the cylindrical portion 130 is pressed against the inner wall of the well 230 by an elastic restoring force, and a frictional force is generated against the force pulling the cylindrical portion 130 out of the well 230. By elastically fitting the cylindrical portion 130 in this way, the septum 100 is detachably fixed to the microplate 200.
[0049] 3 and 4, a slit 140 is formed in the bottom 134 of the cylindrical portion 130. The slit 140 forms a through-hole that passes vertically through the bottom 134 of the cylindrical portion 130. When the septum 100 is attached to the microplate 200, a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer passes through the hole 120 and the inside of the cylindrical portion 130 and is inserted into the slit 140. Note that in FIG. 3, a nozzle 400, which is an example of a thin tube, is indicated by a dashed line.
[0050] A conventional, general septum 100 is configured to assume two states: an inserted state in which a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer is inserted into a well 230 of a microplate 200 through the cylindrical portion 130, and an extracted state in which the thin tube is extracted from the well 230 of the microplate 200 to the outside of the cylindrical portion 130. A slit 140 formed in the bottom portion 134 of the cylindrical portion 130 is structured to open and close by elastic deformation.
[0051] In an automated analyzer, when a capillary tube aspirates liquid from a well 230 or dispenses liquid into a well 230, the relative movement between a predetermined well 230 of the microplate 200 and the tip of the capillary tube is driven. First, the relative movement in the horizontal direction is driven until the predetermined well 230 is positioned below the tip of the capillary tube. Then, the relative movement in the vertical direction is driven.
[0052] In the extraction state, when the well 230 and the tip of the capillary tube are driven to move relative to each other in the vertical direction so that they approach each other, the tip of the capillary tube passes through the hole 120 and the cylindrical portion 130 in the axial direction and is inserted into the well 230 through the slit 140. On the other hand, in the insertion state, when the well 230 and the tip of the capillary tube are driven to move relative to each other in the vertical direction so that they move away from each other, the tip of the capillary tube is extracted from inside the well 230 to the outside of the cylindrical portion 130 and the hole 120.
[0053] In a conventional septum 100, when transitioning from the withdrawn state to the inserted state, the slit 40 is opened by the elastic deformation of the cylindrical portion 130 due to pressure from the thin tube, thereby allowing the thin tube to be inserted. On the other hand, when transitioning from the inserted state to the withdrawn state or in the withdrawn state before insertion, the elastic force of the bottom 134 of the cylindrical portion 130 closes the slit 140, thereby sealing the well 230.
[0054] 4, in a conventional septum 100, the slit 140 is provided as a linear cut in the bottom 134 of the cylindrical portion 130. The cut slit 140 is formed by punching, in which a punch with a thin, linear blade penetrates the bottom 134 of the cylindrical portion 130. In addition, the side surface of the cylindrical portion 130 does not protrude radially outward, but has a flat shape that slides against the inner wall of the well 230.
[0055] In the unloaded state where a thin tube from an automatic analyzer is not inserted and no load is being applied due to pressure from the thin tube, the inner walls of the thin tube are in close contact with each other and the slit 140 is almost completely closed. On the other hand, when a thin tube is inserted, the inner walls of the slit are pushed aside by pressure from the thin tube, and the elastic deformation of the bottom 134 of the cylindrical portion 130 opens slightly, just enough to allow the thin tube to pass through. When the thin tube is pulled out, the elastic restoring force of the bottom 134 of the cylindrical portion 130 returns the slit to an almost completely closed state.
[0056] With such a conventional septum 100, the well 230 containing a sample can be sealed by the elastically opening and closing slit 140 in a state that allows the insertion and removal of a capillary tube into the well 230. This allows the insertion and removal of a capillary tube into the well 230 while preventing evaporation of components from the well 230 and the intrusion of contaminants into the well 230. Because the amount of sample placed in the well 230 is often small, if evaporation progresses before or during analysis, the tip of the capillary tube may be exposed to the gas phase or the concentration of the sample may change. Furthermore, there is a risk of contamination due to the intrusion of suspended matter in the air. However, sealing the well 230 with the septum 100 enables accurate and stable analysis.
[0057] In contrast, the septum 1 according to this embodiment differs from a conventional, general septum 100 in the shape and structure of the bottomed cylindrical portion 30 formed to protrude downward from the main body 10, and in the shape and structure of the slit 40 formed in the bottom 34 of the cylindrical portion 30. In addition, in relation to these differences in shape and structure, the method of sealing the container and the manufacturing process of the septum are also different.
[0058] Fig. 5 is a cross-sectional view showing the structure of the septum according to this embodiment, and Fig. 6 is a perspective view of the cylindrical portion of the septum according to this embodiment as seen from below. 5 and 6, the septum 1 according to this embodiment differs from a conventional septum 100 in that the slit 40 in the bottom 34 of the cylindrical portion 30 is pre-opened. Also, a protrusion 35 is provided on the side surface of the cylindrical portion 30.
[0059] 1 and 2, the holes 20 and the cylindrical portion 30 are arranged in a matrix at intervals on the main body 10 so as to correspond to the wells 230 of the microplate 200. As shown in Fig. 5, the holes 20 and the cylindrical portion 30 form a through structure that passes through the septum 1 from top to bottom.
[0060] The hole 20 has a circular shape in a plan view of the main body 10, and is provided as a through-hole having a substantially inverted truncated cone shape that passes through the main body 10 from top to bottom. One end of the hole 20 opens to the top surface of the main body 10. The other end of the hole 20 opens to the inside of the cylindrical portion 30 on the bottom surface side of the main body 10. The inner diameter of the hole 20 is set to be equal to or smaller than the inner diameter of the well 230. The hole 20 may also be provided as a substantially cylindrical through-hole that passes through the main body 10 from top to bottom.
[0061] The tubular portion 30 has a circular shape in a plan view of the main body 10, and protrudes downward from the periphery of the hole 20 on the underside of the main body 10 in the shape of a cylinder with a bottom. The tubular portion 30 is arranged concentrically with the hole 20. The inner peripheral wall of the tubular portion 30 continues downward from the lower end of the inner peripheral wall of the hole 20. The hole 20 and the tubular portion 30 form a recessed through structure that penetrates the septum 1 from top to bottom.
[0062] The tubular portion 30 is composed of an upper tubular portion 31 having a cylindrical shape and a lower tubular portion 32 having a tapered, bottomed cylindrical shape. The upper tubular portion 31 protrudes cylindrically downward from the periphery of the hole 20 on the underside of the main body 10. The lower tubular portion 32 protrudes downward from the lower end of the upper tubular portion 31 in a tapered shape.
[0063] A cylindrical space is formed inside the upper cylindrical portion 31. A space that is roughly similar in shape to the outer portion is formed inside the lower cylindrical portion 32, and tapers downward. This shape, which tapers downward, allows thin tubes such as capillaries, needles, and nozzles 400 of an automatic analyzer to be properly guided into the slit 40 in the bottom 34 of the cylindrical portion 30.
[0064] 6, the lower tube portion 32 is formed by obliquely cutting out both radially outer sides of a bottomed cylindrical shape so as to have a generally V-shape in a side view of the tubular portion 30. On the cut-out tip side, a bottom portion 34 of the lower tube portion 32 is formed as a flat surface generally perpendicular to the central axis of the tubular portion 30. The bottom portion 34 of the lower tube portion 32 has a rectangular shape in a bottom view of the tubular portion 30. The bottom portion 34 of the lower tube portion 32 is formed on the diameter line of the cut-out tip end surface of the tubular portion 30, and has a rectangular shape with long sides the same length as the diameter.
[0065] The lower tubular portion 32 has inclined side surfaces formed by diagonally cutting out both radially outer sides. Ribs 33 are provided on the inclined side surfaces of the lower tubular portion 32 so as to protrude outward. The ribs 33 are provided symmetrically on both sides with respect to the longitudinal central axis of the bottom portion 34 of the lower tubular portion 32. In a side view of the tubular portion 30, the ribs 33 extend from the lower end of the lower tubular portion 32, where the bottom portion 34 of the lower tubular portion 32 is located, to the upper end of the lower tubular portion 32, where the boundary with the upper tubular portion 31 is located, and are formed as protrusions with a substantially uniform width.
[0066] The ribs 33 extend from the center of each long side of the bottom 34 of the lower tube portion 32 to both sides in a direction perpendicular to the longitudinal direction of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30. The ribs 33 extend in a crisscross pattern relative to the center of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30. The ribs 33 are arranged to sandwich the center of a slit 40 formed in the bottom 34 of the lower tube portion 32 from both outside sides in the short direction of the slit 40.
[0067] That is, the lower tube portion 32 provided with the rib 33 is formed such that both radially outer sides of the bottomed cylindrical shape are thinned obliquely on both left and right sides, leaving the rib 33 at the center. Therefore, the radial outer diameter of the lower tube portion 32 including the rib 33 is equal to the outer diameter of the upper tube portion 31. The outer surface of the rib 33, together with the side surface of the upper tube portion 31, is arranged to slide against the inner wall of the well 230 when the tube portion 30 is inserted into the well 230 of the microplate 200.
[0068] The provision of such ribs 33 ensures that the cylindrical portion 30 can elastically fit into the openings of the wells 230 of the microplate 200 and can slide against the inner walls of the openings of the wells 230, so that the lower side of the cylindrical portion 30 can be made thin while stably fixing the septum 1 to the microplate 200 in a freely detachable manner. When the lower side of the cylindrical portion is thinned, appropriate flexibility and rigidity are obtained, so that the bottom 34 of the lower cylindrical portion 32 around the slit 40 can be elastically deformed appropriately when sealing the wells 230.
[0069] Similar to the case of conventional general septa 100, the cylindrical portion 30 is provided so as to be able to fit inside the openings of multiple wells 230 provided on the microplate 200. When attaching the septa 1 to the microplate 200, each cylindrical portion 30 is inserted into each well 230. The outer diameter of the region of the cylindrical portion 30 excluding the protrusions 35 is set to be equal to or slightly larger than the inner diameter of the well 230. Furthermore, the cylindrical portion 30 and the protrusions 35 are easily elastically deformed by the pressure applied when inserted into the well 230, and are configured so as to be pressed against the inner wall of the well 230 by their elastic restoring force.
[0070] Therefore, when the cylindrical portion 30 and the protrusions 35 are inserted into the well 230, they are pressed from the inner wall of the opening of the well 230 toward the central axis of the cylindrical portion 30, and are slightly elastically deformed so as to be crushed in the radial direction, fitting into the opening of the well 230. After being inserted into the well 230, the cylindrical portion 30 and the protrusions 35 are pressed against the inner wall of the well 230 by an elastic restoring force, and generate a frictional force against the force pulling the cylindrical portion 30 out of the well 230. By elastically fitting the cylindrical portion 30 in this way, the septum 1 is detachably fixed to the microplate 200.
[0071] 6, a slit 40 is formed in the bottom 34 of the cylindrical portion 30. The slit 40 forms a through-hole that passes vertically through the bottom 34 of the cylindrical portion 30. With the septa 1 attached to the microplate 200, a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer passes through the hole 20 and the inside of the cylindrical portion 30 and is inserted into the slit 40.
[0072] The septum 1 according to this embodiment, like a conventional general septum 100, is configured to assume two states: an inserted state in which a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer is inserted into a well 230 of a microplate 200 through the cylindrical portion 30, and an extracted state in which the thin tube is extracted from the well 230 of the microplate 200 to the outside of the cylindrical portion 30. The slit 40 formed in the bottom 34 of the cylindrical portion 30 is configured to open and close by elastic deformation.
[0073] The septum 1 according to this embodiment is configured, like a conventional general septum 100, so that when transitioning from the extracted state to the inserted state, the slit 40 opens due to elastic deformation of the tubular portion 30 caused by pressure from the thin tube, thereby allowing insertion of the thin tube. On the other hand, when transitioning from the inserted state to the extracted state or in the extracted state before insertion, the slit 40 closes due to the elastic force of the tubular portion 30, thereby sealing the well 230.
[0074] 6, in the septum 1 according to this embodiment, the slit 40 is pre-formed in an open shape in the bottom 34 of the cylindrical portion 30. The slit 40 is molded from resin using a molding die that forms the open shape. When the cylindrical portion 30 is removed from the opening of the well 230 or the like, that is, in a non-load state in which no external load is applied to the cylindrical portion 30, the slit 40 has an open shape in which the inner walls of the slit 40 do not abut against each other.
[0075] Furthermore, in the septum 1 according to this embodiment, protrusions 35 are provided on the side surfaces of the cylindrical portion 30. The protrusions 35 protrude radially outward from the side surfaces of the cylindrical portion 30. The protrusions 35 are provided symmetrically on both radially outer sides with respect to the central axis of the cylindrical portion 30. The protrusions 35 are resin-molded integrally with the cylindrical portion 30 using an elastomer that exhibits elasticity.
[0076] 6, slit 40 is provided so that the longitudinal direction of slit 40 is parallel to the longitudinal direction of bottom 34 of lower tube portion 32 when viewed from the bottom of tubular portion 30. With this arrangement, slit 40 is surrounded by bottom 34 of lower tube portion 32, which is made of elastomer with a nearly uniform thickness.
[0077] The protrusions 35 are provided on the outer surface of the rib 33, on the lower side of the side surface of the tubular portion 30, near the bottom 34 of the lower tubular portion 32. When viewed from the bottom of the tubular portion 30, the protrusions 35 are arranged on both sides perpendicular to the longitudinal direction of the bottom 34 of the lower tubular portion 32, with respect to the center of the bottom 34 of the lower tubular portion 32. The protrusions 35 are arranged line-symmetrically on both outer sides with respect to the central axis of the slit 40 in the longitudinal direction, so as to sandwich the center side of the slit 40 from both outer sides in the short direction.
[0078] FIG. 7 is a cross-sectional view showing a method for sealing a container with a septum according to an embodiment of the present invention. 7A and 7B are schematic diagrams showing the state when the cylindrical portion 30 is inserted into the well 230 of the microplate 200. Fig. 7A shows the initial state before the cylindrical portion 30 is inserted. Fig. 7B shows an intermediate state during the insertion of the cylindrical portion 30. Fig. 7C shows the sealed state after the cylindrical portion 30 is inserted.
[0079] 7A, in the initial state, the slit 40 in the bottom 34 of the cylindrical portion 30 is open in the shape molded from the resin. The cylindrical portion 30 is removed from the opening of the well 230 and is in a non-loaded state where no external load is applied. The inner walls of the slit 40 are not in contact with each other, and the slit 40 has almost no effect of sealing the container.
[0080] 7B, in the intermediate state, the cylindrical portion 30 is inserted into the opening of the well 230 up to the height of the protrusion 35. The outer diameter of the region of the cylindrical portion 30 excluding the protrusion 35 is set to be equal to or slightly larger than the inner diameter of the well 230. Meanwhile, the protrusion 35 protrudes radially outward from the side surface of the cylindrical portion 30. Therefore, when attaching the septum 1 to the microplate 200, the cylindrical portion 30 is inserted into the well 230 while the protrusion 35 is pressed inward.
[0081] As shown in FIG. 7C , in the sealed state, substantially the entire tubular portion 30 is inserted into the opening of the well 230. The tubular portion 30 is in a state of elastically fitting inside the opening of the well 230. The protrusions 35 are pressed by the inner walls of the opening of the well 230, causing the tubular portion 30 to elastically deform so as to be crushed in the radial direction. The tubular portion 30 is elastically deformed so as to be crushed in the radial direction, closing the slit 40. The inner walls of the slit 40 come into contact with each other and are closed, thereby achieving the effect of sealing the container.
[0082] 6, the slit 40 is provided so that its longitudinal direction is parallel to the longitudinal direction of the bottom 34 of the lower cylindrical portion 32. The protrusions 35 are arranged to sandwich the center of the slit 40 from both outer sides in the short side direction when viewed from the bottom of the cylindrical portion 30. Therefore, when the protrusions 35 are pressed by the inner wall of the opening of the well 230, the bottom 34 of the lower cylindrical portion 32 elastically deforms to close the slit 40 from both outer sides in the short side direction, thereby closing the slit 40, which is provided in a pre-open shape.
[0083] Slit 40 can be provided so that at least the center of the slit abuts against the inner wall when cylindrical portion 30 is elastically fitted inside the opening of well 230, that is, when protrusion 35 is pressed by the inner wall of the opening of well 230. The occlusion ability due to elastic deformation of slit 40 can be adjusted by adjusting the shape, length, and width of slit 40 and the shape, length, width, height, arrangement, etc. of protrusion 35.
[0084] In an automated analyzer, when using a capillary tube to aspirate liquid from a well 230 or to dispense liquid into a well 230, the capillary tube is inserted into the tubular portion 30 in a sealed state as shown in Fig. 7C. When transitioning from the removed state to the inserted state, the slit 40, which is substantially closed due to elastic deformation caused by pressure from the inner wall of the opening of the well 230, is opened by elastic deformation caused by pressure from the capillary tube. On the other hand, when transitioning from the inserted state to the removed state or in the removed state before insertion, the slit 40 is closed by elastic deformation caused by pressure from the inner wall of the opening of the well 230 and elastic deformation caused by the elastic restoring force of the bottom 34 of the tubular portion 30.
[0085] According to the septum 1 of this embodiment, the protrusions 35 elastically deform the slits 40, which are pre-opened, so that, like conventional general septum 100, a container such as a well 230 containing a sample can be sealed in a state in which a capillary tube can be inserted and removed. This allows the insertion and removal of a capillary tube into and from the container, while preventing evaporation of components from the container and the intrusion of contaminants into the container. Therefore, sealing a container with the septum 1 enables accurate and stable analysis.
[0086] Furthermore, in the septum 1 according to this embodiment, the shape and structure of the slit 40 differ from those of a conventional general septum 100, and therefore the manufacturing process of the septum can be simplified.
[0087] In a conventional, typical septum 100, a cut slit 140 is provided in the bottom 134 of the cylindrical portion 130. The cut slit 140 is formed by a punching process in which a thin, straight-blade punch is passed through the bottom 134 of the cylindrical portion 130.
[0088] However, during punching, the work of attaching the resin-molded septum 100 to a processing jig and the work of transporting the septum 100 with the slits 140 formed therein to the next process must be performed in the air. Since a small amount of processing waste is generated during punching, the use of a clean room is hindered. Furthermore, the punch used in processing may have anti-rust oil, rust, etc., attached to it.
[0089] In conventional manufacturing processes that involve punching, the septum 100 being manufactured may be handled in the air or come into contact with a punch that has foreign matter attached, which can result in contamination of the septum 100. For this reason, a cleaning step is required to clean the septum 100 after punching.
[0090] During punching, individual slits 140 are simultaneously formed in the bottoms 134 of the multiple cylindrical sections 130 arranged in a matrix. The multiple slits 140 are formed by a punch with linear blades arranged in a matrix. Crack-like fracture surfaces are formed at both ends of the cut slits 140 due to the penetration of the thin linear blade.
[0091] During such punching, improper perforation, misalignment, dimensional defects, etc. of the slits 140 may occur. Furthermore, since both ends of the cut slits 140 become cracked fracture surfaces, the cracks tend to propagate at the ends of the slits 140. When a cleaning process is performed after punching, collision forces, etc., are likely to be applied to the protruding cylindrical portion 130, which may cause cracks to propagate at the ends of the slits 140, resulting in dimensional defects of the slits 140 or breakage of the cylindrical portion 130. For this reason, a slit inspection process is required after punching or the cleaning process in which all slits 140 are inspected.
[0092] However, incorporating a cleaning process or a slit inspection process into the septum manufacturing process increases the manufacturing cost of the septum. Liquid-washing of the septum also requires a drying process. The cleaning, drying, and slit inspection processes require labor and equipment costs. Furthermore, the cut slits 140 are almost completely closed unless an external load is applied, making inspection time-consuming due to poor visibility. Furthermore, even if only a portion of the multiple slits 140 or the cylindrical portion 130 suffers from improper perforation, misalignment, or dimensional errors, or if the cylindrical portion 130 is torn, the entire product becomes defective, resulting in a problem of poor yield per product.
[0093] In contrast, with the septum 1 according to this embodiment, the slit 40 is molded from resin into an open shape, eliminating the need to incorporate punching, cleaning, and slit inspection processes into the septum manufacturing process. Because the slit 40 is molded from resin, no processing debris is generated, allowing the septum 1 to be manufactured in a clean room. During manufacturing, the septum 1 does not come into contact with contaminated processing tools or punches, and handling in air is reduced, eliminating the need for a cleaning process. Furthermore, because the slit 40 is open in an unloaded state, dimensions and the like can be easily inspected. Furthermore, because the slit 40 is molded from resin, improper drilling, misalignment, and dimensional errors in the slit 40, as well as breakage of the tubular portion 30 originating from the slit 40, are less likely to occur. Therefore, with the septum 1 according to this embodiment, the manufacturing cost of the septum can be reduced and the yield per unit product can be improved based on the peripheral structure of the slit into which a thin tube such as a capillary, needle, or nozzle 400 is inserted.
[0094] Furthermore, according to the septum 1 of this embodiment, the shape and structure of the cylindrical portion 30 and the shape and structure of the slit 40 provide the effect of reducing sample carryover in an automatic analyzer.
[0095] In an automated analyzer, when a capillary tube aspirates liquid from a well 230 or dispenses liquid into a well 230, the liquid may adhere to the side of the tip of the capillary tube. If liquid adheres to the capillary tube, when the capillary tube is inserted into another well 230, the liquid may be carried over, i.e., carryover may occur. Carryover can lead to changes in sample concentration and cross-contamination. For this reason, it is necessary to remove the liquid adhering to the tip of the capillary tube and to clean the tip of the capillary tube.
[0096] In a conventional septum 100, the slit 140 in the bottom 134 of the cylindrical portion 130 is formed as a linear cut. Therefore, when the capillary tube is pulled out of the well 230, the inner walls of the cut slit 140, which have been pushed aside by the pressure from the capillary tube, return to their original positions due to elastic restoring force until they come into close contact with each other. During this process, the liquid adhering to the side of the tip of the capillary tube can be wiped away to a certain extent by the inner walls of the cut slit 140 that return to their original positions.
[0097] However, the bottom 134 of the cylindrical portion 130, where the cut slit 140 is provided, is thin enough to allow a thin, straight-blade punch to penetrate. If the inner wall of the slit 140 is thin, when the inner wall is pushed aside by pressure from the capillary tube, the elastic restoring force that attempts to return to its original shape is weak. Therefore, conventional, typical septa 100 are not able to sufficiently wipe away liquid adhering to the side surface of the tip of the capillary tube. The technology described in Patent Document 1 only utilizes the elastic force of the material deformed by pressure from the capillary tube, so there is a possibility that the load applied to the side surface of the tip of the capillary tube is insufficient.
[0098] In contrast, in septum 1 according to this embodiment, protrusions 35 are formed on the side surfaces of cylindrical portion 30, and pressure from the inner wall of the opening of well 230 against protrusions 35 elastically deforms slit 40 to close it from both outside in the short direction, thereby making it possible to strengthen the elastic restoring force of slit 40 to return to its original shape more than ever before. Because the inner wall of slit 40 elastically deforms in the closing direction due to pressure from protrusions 35 before elastically deforming in the opening direction due to pressure from the capillary, when the capillary is pulled out of well 230, the load due to the elastic force on the side surfaces of the tip of the capillary becomes stronger than ever before.
[0099] The load due to the elastic force applied from the slit 40 to the tip of the capillary tube can be adjusted, for example, by adjusting the shape, length, width, height, and arrangement of the protrusions 35 and the thickness of the bottom 34 of the tubular portion 30. Adjusting the load due to the elastic force applied to the tip of the capillary tube to strengthen the action of wiping off liquid adhering to the side of the tip of the capillary tube reduces carryover, thereby suppressing changes in sample concentration and cross-contamination.
[0100] Furthermore, in the septum 1 according to this embodiment, the slits 40 are resin-molded into a pre-opened shape, which improves the durability of the structure surrounding the slits 40 compared to conventional cut-out slits 140. Even if an external force is applied to the protruding tubular portion 30 when the septum 1 is attached or stored, tears at the ends of the slits 40 and breakage of the tubular portion 30 are reduced, resulting in a septum 1 with high durability.
[0101] FIG. 8 is a bottom view of the cylindrical portion of the septum showing examples of the shape of the slit. Fig. 8 shows an example of the shape of the slit 40 when the cylindrical portion 30 is removed from the opening of the container. As shown in Fig. 8, the slit 40 in the bottom 34 of the cylindrical portion 30 can be provided so as to open into an appropriately flat shape with a large aspect ratio.
[0102] Fig. 8A is a diagram showing a rectangular slit 40a. Fig. 8B is a diagram showing an elliptical slit 40b. Fig. 8C is a diagram showing an oval slit 40c. Fig. 8D is a diagram showing a diamond slit 40d. Fig. 8E is a diagram showing a mouth slit 40e. Fig. 8F is a diagram showing a spear slit 40f.
[0103] The oval-shaped slit 40c is a flat rectangular shape with the short side formed in a semicircular arc. The mouth-shaped slit 40e is formed by joining two flat normal distribution curves together to form a closed curve. The spear-shaped slit 40f is a flat hexagon.
[0104] As shown in Figures 8A to 8F, the flat-shaped slits 40a, 40b, 40c, 40d, 40e, and 40f are formed so that the longitudinal direction of each slit 40a, 40b, 40c, 40d, 40e, and 40f is parallel to the longitudinal direction of the bottom 34 of the lower tube portion 32.
[0105] The protrusions 35 are arranged in a direction perpendicular to the longitudinal direction of the bottom 34 of the lower tube portion 32 with respect to the centers of each long side of the bottom 34 of the lower tube portion 32 in a bottom view of the tubular portion 30. The protrusions 35 are arranged line-symmetrically on both outer sides with respect to the central axis of each of the slits 40a, 40b, 40c, 40d, 40e, and 40f in the longitudinal direction, so as to sandwich the center sides of each of the slits 40a, 40b, 40c, 40d, 40e, and 40f from both outer sides in the short direction.
[0106] For example, when the inner diameter of the well 230 is 5 mm, the longitudinal length of each of the slits 40a, 40b, 40c, 40d, 40e, and 40f can be set to 2.8 mm or more and 3.2 mm or less. The lateral width can be set to 0.5 mm or less. The height of the protrusion 35, i.e., the radial length of the cylindrical portion 30 as viewed from the bottom, can be set to 0.25 mm or more and 0.4 mm or less. The thickness of the bottom of the cylindrical portion 30 can be set to 1 mm or more or less than 1 mm, depending on factors such as the load due to the elastic force applied to the tip of the thin tube.
[0107] As shown in Fig. 8A, rectangular slits 40a have the disadvantage that when pressure is applied from the inner wall of the container to protrusions 35, openings remain at both longitudinal ends of slits 40a. However, this has the advantage that the mold for molding slits 40a into resin has a simple shape, making it easy to manufacture. Also, because the core side of the mold does not have a narrow shape at the position corresponding to slits 40a, the mold is less likely to break.
[0108] As shown in Figure 8B, the oval slit 40b has the disadvantage of being prone to cracking because both longitudinal ends of the slit 40b are narrow. Also, the core side of the mold has a narrow shape at positions corresponding to both longitudinal ends of the slit 40b, making the mold prone to breakage. However, when pressure is applied from the inner wall of the container to the protrusion 35, openings are unlikely to remain at both longitudinal ends of the slit 40b, which has the advantage of providing a high level of sealing.
[0109] As shown in Figure 8C, the oval-shaped slit 40c has the disadvantage that when pressure is applied from the inner wall of the container to the protrusion 35, openings remain at both longitudinal ends of the slit 40c. However, this has the advantage that the molding die for molding the slit 40c into the resin has a simple shape, making it easy to manufacture. Also, since the core side of the molding die does not have a narrow shape at the position corresponding to the slit 40c, the molding die is less likely to break.
[0110] As shown in Figure 8D, the diamond-shaped slit 40d has the disadvantage of being prone to cracking because both longitudinal ends of the slit 40d have acute angles. Furthermore, the core side of the mold has acute angles at positions corresponding to both longitudinal ends of the slit 40d, making the mold prone to breakage. However, when pressure is applied from the inner wall of the container to the protrusion 35, openings are unlikely to remain at both longitudinal ends of the slit 40d, providing the advantage of high sealing performance.
[0111] As shown in Figure 8E, the slit 40e that opens in a mouth shape has the disadvantage of being prone to cracking because both longitudinal ends of the slit 40e form sharp points. Furthermore, the core side of the mold has sharp points at positions corresponding to both longitudinal ends of the slit 40e, making the mold prone to breakage. However, when pressure is applied from the inner wall of the container to the protrusion 35, openings are unlikely to remain at both longitudinal ends of the slit 40e, which is an advantage in that a high level of sealing is achieved.
[0112] As shown in Figure 8F, the spear-shaped slit 40f has the disadvantage of being prone to cracking because both longitudinal ends of the slit 40f have acute angles. Furthermore, the core side of the mold has acute angles at positions corresponding to both longitudinal ends of the slit 40f, making the mold prone to breakage. However, when pressure is applied from the inner wall of the container to the protrusion 35, openings are unlikely to remain at both longitudinal ends of the slit 40f, providing the advantage of high sealing performance.
[0113] FIG. 9 is a perspective view of the cylindrical portion of the septum, showing examples of the shape of the protrusions, as viewed from below. 9 shows examples of the shape of the protrusion 35 provided on the side surface of the cylindrical portion 30. The protrusion 35 protrudes radially outward from the side surface of the cylindrical portion 30, and can be provided in any suitable shape and arrangement as long as it closes the slit 40, which is provided in advance in an open shape, by pressure from the inner wall of the container.
[0114] Fig. 9A is a diagram showing a cylindrical portion 30 provided with rib-like protrusions 35a, Fig. 9B is a diagram showing a cylindrical portion 30 provided with auxiliary protrusions 35b in addition to the rib-like protrusions 35a, and Fig. 9C is a diagram showing a cylindrical portion 30 provided with blade-like protrusions 35c.
[0115] 9A, the rib-like protrusions 35a are provided in a rib-like manner on the inclined side surfaces of the lower tubular portion 32 so as to protrude outward from the side surfaces of the lower tubular portion 32. The rib-like protrusions 35a are provided symmetrically on both outer sides in the radial direction with respect to the central axis of the lower tubular portion 32. In a side view of the tubular portion 30, the rib-like protrusions 35a extend from the lower end of the lower tubular portion 32, where the bottom 34 of the lower tubular portion 32 is located, to the upper end of the lower tubular portion 32, where the boundary with the upper tubular portion 31 is located, and are formed as ridges with a substantially uniform width.
[0116] The rib-like protrusions 35a extend outward on both sides in a direction perpendicular to the long sides of the bottom 34 of the lower tube portion 32 from the center of the long side of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30. The rib-like protrusions 35a are arranged so as to cross the center of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30, and are arranged so as to sandwich the center of the slit 40 formed in the bottom 34 of the lower tube portion 32 from both outer sides in the short direction.
[0117] The rib-shaped protrusions 35a are provided on the lower side near the bottom 34 of the lower tubular portion 32, so as to protrude radially outward beyond the main portion of the lower tubular portion 32. The lower side of the rib-shaped protrusions 35a protrudes outward beyond the outer circumferential surface of the upper tubular portion 31 and the outer circumferential surface of the region of the lower tubular portion 32 excluding the protrusions 35a. When viewed from the bottom of the tubular portion 30, the maximum outer diameter of the rib-shaped protrusions 35a is larger than the outer diameter of the lower tubular portion 32.
[0118] By providing such rib-like protrusions 35a, the elastic fit of tubular portion 30 with the openings of wells 230 of microplate 200, the sliding contact with the inner walls of the openings of wells 230, and the closure of slits 40 can be adjusted integrally based on the shape of rib-like protrusions 35a. Furthermore, compared to when protrusions 35 are provided individually, the shape of the molding die is simpler, making it easier to fabricate the molding die.
[0119] 9A, the lower side of the rib-shaped protrusion 35a protrudes in an obtuse triangular shape in a side view of the rib-shaped protrusion 35a. Such a mountain shape makes it less likely for the tubular portion 30 to interfere with the opening of the well 230 when inserted into the inside of the opening of the well 230. The rib-shaped protrusion 35a is inserted linearly into the well 230, which improves the closure of the slit 40 due to elastic deformation. However, the lower side of the rib-shaped protrusion 35a can also be formed in an arc shape, a rectangle shape, a trapezoid shape, or the like.
[0120] As shown in FIG. 9B , auxiliary protrusions 35b can be provided on the side surface of the tubular portion 30 in addition to the rib-like protrusions 35a. The auxiliary protrusions 35b are provided on the inclined side surface of the lower tubular portion 32 so as to protrude outward from the side surface of the lower tubular portion 32. Similar to the rib-like protrusions 35a, the auxiliary protrusions 35b are provided symmetrically on both outer sides in the radial direction with respect to the central axis of the lower tubular portion 32. The auxiliary protrusions 35b are also provided symmetrically on both outer sides of the rib-like protrusions 35a so as to sandwich the rib-like protrusions 35a. The auxiliary protrusions 35b are formed as ridges with a substantially uniform width and extend parallel to the rib-like protrusions 35a.
[0121] The auxiliary protrusions 35b extend outward from both ends of each long side of the bottom 34 of the lower tube portion 32 in a direction perpendicular to the long sides of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30. The auxiliary protrusions 35b are provided so as to intersect with the ends of the bottom 34 of the lower tube portion 32, when viewed from the bottom of the tubular portion 30, and are arranged so as to sandwich both ends of the slit 40 formed in the bottom 34 of the lower tube portion 32 from both outside in the short direction.
[0122] The auxiliary protrusion 35b is provided on the lower side near the bottom 34 of the lower tube portion 32, so as to protrude radially outward beyond the main portion of the lower tube portion 32. The auxiliary protrusion 35b protrudes outward beyond the outer peripheral surface of the upper tube portion 31 and the outer peripheral surface of the region of the lower tube portion 32 excluding the protrusion 35a. When viewed from the bottom of the tubular portion 30, the maximum outer diameter of the auxiliary protrusion 35b is larger than the outer diameter of the lower tube portion 32.
[0123] Providing such auxiliary protrusions 35b can reduce the size of the openings at both longitudinal ends of slit 40, which is likely to remain when tubular portion 30 is inserted into well 230. When auxiliary protrusions 35b are pressed by the inner wall of the opening of well 230, they elastically deform both longitudinal ends of slit 40 so that they collapse. Therefore, the closure of slit 40 can be improved compared to when protrusions are provided only at positions that cross the center of bottom 34 of lower tubular portion 32.
[0124] 9B, auxiliary protrusion 35b protrudes in the shape of an obtuse triangle in a side view of auxiliary protrusion 35b. Such a mountain shape makes it less likely for the cylindrical portion 30 to interfere with the opening of well 230 when inserted into the opening of well 230. Because auxiliary protrusion 35b is inserted linearly into well 230, it improves the closure of slit 40 through elastic deformation. However, auxiliary protrusion 35b may also be formed in an arc-like, rectangular, trapezoidal, or other shape.
[0125] 9B, auxiliary protrusions 35b are provided parallel to rib-like protrusions 35a, but auxiliary protrusions 35b can also be provided so as to protrude radially outward in the radial direction of lower tubular portion 32. When auxiliary protrusions 35b are provided so as to protrude radially, both longitudinal ends of slit 40 can be elastically deformed so as to be crushed toward the central axis of tubular portion 30 when pressed by the inner wall of the opening of well 230.
[0126] 9C, wing-like protrusions 35c may be provided on the side surfaces of the tubular portion 30. The wing-like protrusions 35c are provided in a wing-like shape on the side surfaces of the upper tubular portion 31 and the inclined side surfaces of the lower tubular portion 32, protruding outward from the side surfaces of the upper tubular portion 31 and the lower tubular portion 32. The wing-like protrusions 35c are provided symmetrically on both outer sides in the radial direction with respect to the central axis of the upper tubular portion 31 and the lower tubular portion 32. The wing-like protrusions 35c extend from the lower end of the lower tubular portion 32, where the bottom portion 34 of the lower tubular portion 32 is located, to the upper end of the upper tubular portion 31, in a side view of the tubular portion 30, and are formed as thin wing-like plates with a substantially uniform width.
[0127] The wing-like protrusions 35c extend outward on both sides in a direction perpendicular to the long sides of the bottom 34 of the lower tube portion 32 from the center of the long side of the bottom 34 of the lower tube portion 32 in a bottom view of the tubular portion 30. The wing-like protrusions 35c are arranged to cross the center of the bottom 34 of the lower tube portion 32 in a bottom view of the tubular portion 30, and are arranged to sandwich the center of the slit 40 formed in the bottom 34 of the lower tube portion 32 from both outer sides in the short direction.
[0128] The wing-shaped protrusions 35c are shaped to protrude radially outward beyond the main body sides of the upper tube portion 31 and the lower tube portion 32. The upper side of the wing-shaped protrusions 35c protrudes radially outward beyond the outer peripheral surface of the region of the upper tube portion 31 excluding the protrusions 35c. The lower side of the wing-shaped protrusions 35c protrudes radially outward beyond the outer peripheral surface of the region of the lower tube portion 32 excluding the protrusions 35c. When viewed from the bottom of the tube portion 30, the maximum outer diameter of the wing-shaped protrusions 35c is larger than the outer diameter of the main body sides of the upper tube portion 31 and the lower tube portion 32.
[0129] By providing such wing-like protrusions 35c, the elastic fit of tubular portion 30 with the openings of wells 230 of microplate 200, the sliding contact with the inner walls of the openings of wells 230, and the closure of slits 40 can be adjusted integrally based on the shape of wing-like protrusions 35c. Furthermore, compared to the case where rib-like protrusions 35a are provided, the upper side of tubular portion 30 is also more easily pressed by the inner walls of wells 230, resulting in a structure that makes it easy to utilize not only elastic deformation in the radial direction of the lower side of tubular portion 30 but also elastic deformation in the axial direction of tubular portion 30.
[0130] 9C, the lower side of the wing-like protrusion 35c protrudes in the shape of an obtuse triangle in a side view of the wing-like protrusion 35c. Such a mountain shape makes it less likely for the tubular portion 30 to interfere with the opening of the well 230 when it is inserted into the opening of the well 230. Because the wing-like protrusion 35c is inserted linearly into the well 230, the slit 40 is well closed by elastic deformation. However, the lower side of the wing-like protrusion 35c may also be formed in an arc shape, a rectangle shape, a trapezoid shape, or the like.
[0131] 1 and 2, the microplate 200 is a 96-well microplate, and the septa 1 is for use with the 96-well microplate, but the septa 1 according to this embodiment may be provided for use with a microplate having any number of wells 230. For example, it may be provided for use with a 24-well microplate, a 48-well microplate, a 384-well microplate, etc.
[0132] 1 and 2, the septa 1 is for a microplate, but the septa 1 according to this embodiment may be provided as a multiple container having a plurality of arranged container portions, such as a multiple microtube, a multiple microvial, or a multiple electrophoresis medium container of a capillary electrophoresis device.
[0133] FIG. 10 is a perspective view showing a septum and a multiple microtube according to an embodiment of the present invention. FIG. 10 illustrates a septum 2 for a multiple microtube, and a multiple microtube 300 to which the septum 2 is attached, as an example of a septum according to this embodiment.
[0134] The multiple microtube 300 is used as a container in analysis, inspection, experiments, etc. The multiple microtube 300 has a structure in which a plurality of microtubes 310 are connected in parallel. The multiple microtube 300 is made of a polyolefin such as polypropylene, polyethylene, or polystyrene.
[0135] The microtube 310 has a circular shape in a plan view and is provided as a tapered, approximately cylindrical container. The top of the microtube 310 has a circular opening facing upward. Inside the microtube 310, a cylindrical space is formed that tapers downward in diameter. The space inside the microtube 310 functions as a container, similar to the well 230 of the microplate 200, and a desired liquid or the like is placed therein.
[0136] 10, the multiple microtube 300 is an eight-tube microtube in which a total of eight microtubes 310 are connected. The microtubes 310 are connected to each other via a strip-shaped portion connected to the upper part. However, the number of connected multiple microtubes 300, the capacity, the inner diameter, the outer diameter, the connection structure, etc. may be any appropriate condition.
[0137] 10, the microtube 310 is provided as a tapered, generally cylindrical container, but there is no particular limitation on the shape of the microtube 310. For example, the microtube 310 may be provided as a generally cylindrical microvial or the like.
[0138] Similar to the microplate 200, the multiple microtube 300 can be used as a container for setting samples in an automatic analyzer equipped with an autosampler. The multiple microtube 300 can be set in the automatic analyzer by being supported on a rack or the like provided with support holes for inserting the microtubes 310.
[0139] As shown in Figure 10, the septum 2 of this embodiment, like the septum 1 for the microplate described above, comprises a main body 10 formed in a sheet-like shape, a plurality of hole portions 20 penetrating the main body 10 from top to bottom, bottomed tubular portions 30 formed to protrude downward from around each of the hole portions 20 on the underside of the main body 10, and slits 40 formed in the bottom of each of the tubular portions 30.
[0140] The septum 2 according to this embodiment, like the septum 1 for a microplate, has the function of sealing the microtubes 310 of the multiple microtube 300 in a state in which thin tubes such as capillaries, needles, and nozzles 400 of an automatic analyzer can be inserted into and removed from the microtubes 310. The septum 2 is attached to the upper side of the multiple microtube 300 after a sample has been placed in the microtubes 310 of the multiple microtube 300 and before the multiple microtube 300 is set in the automatic analyzer.
[0141] The main body 10, hole 20, and cylindrical portion 30 of the septum 2 can be integrally resin-molded from an elastic elastomer, similar to the septum 1 for the microplate described above. Examples of materials for the septum 2 include silicone rubber, fluororubber, and ethylene-propylene-diene rubber (EPDM). The main body 10 can be formed to have a width approximately equal to the outer diameter of the microtube 310 and a length approximately equal to the outer dimension of the microtube 310 in the connecting direction.
[0142] In the septa 2, a structural unit that seals the microtube 310 of the multiple microtube 300 in a state in which a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer can be inserted and removed can be provided, similar to the septa 1 for a microplate. The slit 40 in the bottom 34 of the cylindrical portion 30 is formed in a pre-open shape. In addition, a protrusion 35 is provided on the side surface of the cylindrical portion 30.
[0143] Similar to the septum 1 for a microplate described above, the septum 2 according to this embodiment is configured to be in an inserted state in which a thin tube such as a capillary, needle, or nozzle 400 of an automatic analyzer is inserted into the microtube 310 of the multiple microtube 300 through the tubular portion 30, and in an extracted state in which the thin tube is extracted from the microtube 310 of the multiple microtube 300 to the outside of the tubular portion 30. The slit formed in the bottom of the tubular portion 30 is structured to open and close by elastic deformation.
[0144] The septum 2 according to this embodiment, like the septum 1 for a microplate described above, is configured so that when transitioning from the extracted state to the inserted state, the slit opens due to elastic deformation of the tubular portion 30 caused by pressure from the thin tube, thereby allowing the thin tube to be inserted. On the other hand, when transitioning from the inserted state to the extracted state or in the extracted state before insertion, the slit closes due to the elastic force of the tubular portion 30, thereby sealing the well 230.
[0145] Such a septum 2 can seal the microtube 310 containing a sample in a state in which the capillary tube can be inserted and removed by using a slit that opens and closes elastically. This allows the insertion and removal of a capillary tube into and from the microtube 310, while preventing evaporation of components from the microtube 310 and the intrusion of contaminants into the microtube 310. Sealing the microtube 310 with the septum 2 enables accurate and stable analysis.
[0146] The septum 2 according to this embodiment, like the septum 1 for a microplate described above, differs from the conventional general septum 100 in the shape and structure of the bottomed cylindrical portion 30 formed to protrude downward from the main body portion 10, and in the shape and structure of the slit 40 formed in the bottom portion 34 of the cylindrical portion 30. In addition, in relation to these differences in shape and structure, the method of sealing the container and the manufacturing process of the septum are also different.
[0147] The septum 2 according to this embodiment, like the septum 1 for a microplate described above, has a slit 40 in the bottom 34 of the cylindrical portion 30 that is pre-opened. Furthermore, a protrusion 35 is provided on the side surface of the cylindrical portion 30. As shown in FIG. 8, the slit 40 can be provided so as to open into a flat shape with a high aspect ratio, such as a rectangle, ellipse, oval, diamond, mouth, or spear shape. As shown in FIG. 9, the protrusion 35 can be provided as a combination of a rib-like protrusion 35a and an auxiliary protrusion 35b, or as a wing-like protrusion 35c.
[0148] According to the septum according to the present embodiment, the manufacturing process of the septum is simplified based on the structure around the slit, thereby reducing the manufacturing cost of the septum and improving the yield per product. Therefore, compared to septums with conventional cut slits, septums can be provided at a lower cost. Furthermore, sample carryover in an automated analyzer can be reduced, enabling more accurate analysis. Furthermore, compared to septums with conventional cut slits, a product with higher durability around the slit can be obtained.
[0149] Although the present invention has been described above, the present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the present invention. For example, the present invention is not necessarily limited to those having all of the configurations of the above-described embodiments. It is possible to replace part of the configuration of an embodiment with another configuration, add part of the configuration of an embodiment to another form, or omit part of the configuration of an embodiment.
[0150] Although the septa according to the above-described embodiments are intended for use with microplates and multiple microtubes, the septa according to the above-described embodiments can be applied to a plurality of arranged containers and a multiple-container container having a plurality of arranged container portions integrated together, in addition to microplates and multiple microtubes. The container capacity is not limited to the micron order, and the septa can be applied to containers and container portions of any appropriate capacity. The septa may be a separate accessory that is stacked on the plate during use, or may be integrated into the underside of a highly rigid lid member. [Explanation of symbols]
[0151] 1 Septa 2 Septa 10 Main body 20 Hole 30 Cylindrical part 31 Upper cylinder part 32 Lower cylinder part 33 Ribs 34 Bottom 35 Protrusion 40 slits 100 septa 110 Main body 120 Hole 130 Cylindrical part 140 slit 200 microplates 210 recess 220 Outer Frame 230 wells (containers) 231 Upper 232 Lower 300 multi-tube microtubes 310 Microtube (container) 400 nozzle (thin tube)
Claims
1. The container has a plurality of cylindrical portions that can be fitted into the openings of the plurality of arranged containers, and a slit formed in the bottom of each of the cylindrical portions, When the cylindrical portion is fitted into the opening, the device is configured to assume an inserted state in which a thin tube for sucking or discharging liquid into the container is inserted into the container through the cylindrical portion, and a removed state in which the thin tube is removed from the container to the outside of the cylindrical portion, When the state transitions from the removed state to the inserted state, the slit is opened by elastic deformation of the cylindrical portion due to pressure from the thin tube, thereby allowing insertion of the thin tube; a septum that closes the slit by an elastic force of the cylindrical portion to seal the container when transitioning from the inserted state to the removed state, the cylindrical portion has a protrusion protruding radially outward from a side surface, the protrusions are arranged so as to sandwich the slit from both outer sides in a short direction of the slit, but not to sandwich the slit from both outer sides in a long direction of the slit, The slit is formed in an open shape such that the inner walls of the slit do not abut against each other when the cylindrical portion is removed from the opening, and when the cylindrical portion is fitted inside the opening, the protrusion is pressed by the inner wall of the container, and the cylindrical portion is elastically deformed by the pressure, closing the septum to seal the container.
2. 10. The septum of claim 1, The slit is provided to open in a rectangular, elliptical, oval, diamond, mouth, or spear shape.
3. A device comprising a plurality of cylindrical portions that can be fitted inside the openings of a plurality of arranged containers, and slits formed in the bottoms of the respective cylindrical portions; When the cylindrical portion is fitted into the opening, the device is configured to assume an inserted state in which a thin tube for sucking or discharging liquid into the container is inserted into the container through the cylindrical portion, and a removed state in which the thin tube is removed from the container to the outside of the cylindrical portion, When the state transitions from the removed state to the inserted state, the slit is opened by elastic deformation of the cylindrical portion due to pressure from the thin tube, thereby allowing insertion of the thin tube; a septum that closes the slit by an elastic force of the cylindrical portion to seal the container when transitioning from the inserted state to the removed state, the cylindrical portion has a protrusion protruding radially outward from a side surface, an upper cylindrical portion provided in a cylindrical shape, and a lower cylindrical portion provided in a shape in which both radially outer sides of the bottomed cylindrical shape are obliquely cut out so as to present a V-shape in side view, the bottom of the cylindrical portion is a bottom of the lower cylindrical portion that has a rectangular shape when viewed from the bottom of the cylindrical portion, The slit is formed in an open shape such that the inner walls of the slit do not abut against each other when the cylindrical portion is removed from the opening, and when the cylindrical portion is fitted inside the opening, the protrusion is pressed by the inner wall of the container, and the cylindrical portion is elastically deformed by the pressure, closing the septum to seal the container.
4. 4. The septum of claim 3, the slit is formed in a bottom portion of the lower cylindrical portion, which has a rectangular shape when viewed from the bottom of the cylindrical portion, and is parallel to a longitudinal direction of the bottom portion of the lower cylindrical portion, The protrusions are septa that are arranged to sandwich the center of the slit from both outside sides in the short direction of the slit.
5. 5. The septum of claim 4, The protrusion is a septum provided as a rib-like protrusion protruding outward from the side surface of the lower cylindrical portion, or as a blade-like protrusion protruding outward from the side surfaces of the upper cylindrical portion and the lower cylindrical portion.
6. 6. The septum according to claim 1, the container is a well provided on a microplate, The septum is a septum for a microplate.
7. 6. The septum according to claim 1, the container is a plurality of microtubes connected to each other, The septum is a septum for a multi-unit microtube in which a plurality of microtubes are connected to each other.
8. 6. The septum according to claim 1, The thin tube is a septum, which is a capillary, needle or nozzle provided in an automatic analyzer.
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