Micro storage container
The micro-storage container addresses the challenge of extracting small biological samples by ensuring sufficient height and stability, enabling easy handling and extraction of the upper layer, particularly for non-medical personnel.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-09-20
- Publication Date
- 2026-04-02
AI Technical Summary
Existing methods face difficulties in extracting the upper layer of small biological samples using pipettes due to insufficient height and handling challenges, especially for non-medical personnel.
A micro-storage container with a cylindrical design that tapers towards the top, ensuring sufficient height in the upper layer post-separation, and is self-supporting, featuring a lower cylindrical portion with a narrow diameter and gentle/steep sloping sections to facilitate easy extraction.
Facilitates easy extraction of the upper layer even with small samples, enhances handling for non-medical personnel, and maintains separation stability during transport.
Smart Images

Figure 2026056909000001_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a storage container that stores a small amount of a sample such as a collected biological sample and can be installed in a centrifuge.
Background Art
[0002] Recently, for medical purposes, various methods for collecting, separating, and extracting specific components from biological samples have been used. These methods collect specific components of biological samples (such as blood, lymph fluid, urine, sputum, feces, etc.) in a container. As one device for separating specific components of a biological sample, a centrifuge using centrifugal force can be mentioned.
[0003] This centrifuge installs a container storing a biological sample on a rotor and rotates it at a predetermined rotational speed to apply centrifugal force to the biological sample, thereby separating the components of the biological sample into layers according to the specific gravity difference. At that time, components with a high specific gravity form a layer at the lower part of the sample, and components with a low specific gravity form a layer at the upper part of the sample. By collecting each of these separated layers individually, specific components of the biological sample can be obtained.
[0004] As a container that can be installed and used in such a centrifuge, a container including a specimen storage tool in which a drug is held in advance, a sample collection tool for collecting a sample, and a lid member has been conventionally known (for example, Patent Document 1, etc.). Specifically, the sample collection container described in Patent Document 1 is composed of a sample collection tool, a specimen storage tool, and a specimen sealing lid. The specimen storage tool is composed of a specimen storage tool body and a sample collection tool bottom lid. The sample collection tool can be inserted into the specimen storage tool body, and the inserted sample collection tool is held by the sample collection tool bottom lid provided at the bottom of the specimen storage tool body, and the lower opening of the sample collection tool is sealed. The specimen storage tool body into which the sample collection tool is inserted is sealed by the sample collection tool bottom lid and the specimen sealing lid, so that the sample in the sample collection tool can be centrifuged, stored, or transported.
Prior Art Documents
[0005] [Patent Document 1] International Publication No. 2016 / 147748 [Overview of the project] [Problems that the invention aims to solve]
[0006] Incidentally, in recent years there has been a growing need for less invasive blood tests, and there is a demand for testing methods that use minute samples taken from the fingertip. In blood tests, the upper layer separated by centrifugation is sometimes used for testing, but when the sample is very small, the upper layer is also very small, making extraction with instruments such as pipettes difficult.
[0007] In view of the above circumstances, the present invention aims to provide a storage container that can secure sufficient height in the upper layer even with a small amount of sample, and that facilitates extraction operations using instruments such as pipettes. [Means for solving the problem]
[0008] To solve the above-mentioned problems, the present invention employs the following configuration. That is, A micro-storage container for storing liquid samples, It comprises a cylindrical main body member having an internal space that is open only at the top, and a sealing member that seals the opening, The internal space comprises a sealed portion into which the sealing member is inserted, an upper cylindrical portion located below the sealed portion and forming a liquid containment space, and a portion connected to the upper cylindrical portion at a different angle. It is divided into a lower cylindrical section where the inner diameter decreases towards the lower end, The lower cylindrical portion has an axial length of 50% or more of the axial length from the opening to the bottom surface of the internal space located on the opposite side of the opening, in this micro-storage container.
[0009] With this configuration, the internal space tapers towards the top and is open only at the top, making it easy for the sample's liquid level to be positioned higher in the container. Furthermore, even with a small amount of sample, sufficient height can be ensured in the upper layer after separation, making extraction with instruments easier.
[0010] Furthermore, the main body member may be integrally formed with the wall portion forming the internal space, and may have an outer wall portion whose lower end is located lower than the lower cylindrical portion, and the outer wall portion may be configured to be self-supporting with its lower end as the bottom. With such a configuration, the container can be made self-supporting via the outer wall portion, so the user does not need to hold the container while performing the blood collection procedure. For this reason, a micro-storage container that is easy to handle can be provided even for non-medical personnel who are not familiar with the blood collection procedure.
[0011] Furthermore, the lower cylindrical portion has a narrow diameter region having a diameter of 1 / 2 or less of the maximum diameter dimension in the internal space, and the narrow diameter region may extend axially such that it has an axial dimension of 30% or more of the axial length in the internal space. With this configuration, the internal space tapers towards the top and is open only at the top, making it easy for the liquid level of the sample to be located at the top of the container. Also, even if the sample is in a small amount, sufficient width in the height direction of the upper layer can be secured after separation, making it easy to perform extraction operations with instruments.
[0012] Furthermore, the lower cylindrical portion may have a gently sloping portion located in the axial middle of the internal space and gently inclined with respect to the direction perpendicular to the axis, and a steeply sloping portion located below the gently sloping portion and inclined at a steeper angle than the gently sloping portion with respect to the direction perpendicular to the axis. With such a configuration, it is easy to form a narrow-diameter region with the steeply sloping portion, and it is easy to position the liquid surface of the sample above the container. In addition, because the gently sloping portion is located in the axial middle of the internal space, it is easy to position the upper layer after separation of the sample in a space with a relatively wide inner diameter, improving the operability of sampling with instruments such as pipettes.
[0013] Furthermore, the main body member may have a tapered wall portion that forms the lower cylindrical portion on the inside of the outer wall portion, and a gap may be formed between the outer wall portion and the tapered wall portion. With such a configuration, the outer wall portion prevents external force from being applied to the tapered wall portion, and prevents the tapered wall portion from being unintentionally damaged.
[0014] Furthermore, the bottom of the internal space may be positioned above the lower end of the outer wall. This configuration prevents external forces from being applied to the bottom, thus preventing unintentional damage to the bottom.
[0015] Furthermore, the sealing member may seal the opening of the main body member by contacting the outer and inner surfaces of the main body member. With such a configuration, the airtightness of the container can be increased. In particular, it is preferable that the sealing member is compressed radially inward by the inner surface of the main body member, so that when the sealing member is pushed into the container, the portion of the sealing member that contacts the inner wall of the container is compressed, thereby suppressing the cap from floating over time. It is also preferable that the sealing member is compressed radially on the outer surface side of the main body member. If the inner surface of the main body member has a slight taper, the compression may weaken when the cap floats, potentially reducing the sealing performance against the inner surface of the main body member. However, by keeping the outer surface of the main body member compressed with the sealing member, even if a slight misalignment occurs, the sample can still be prevented from leaking out.
[0016] The main body member may have a flange portion that protrudes radially outward, and may be mounted on the centrifuge via the flange portion. With this configuration, since the main body member is mounted on the centrifuge, the centrifugation operation can be performed more stably than when the sealing member is mounted on the centrifuge (i.e., when the part supported by the centrifuge is the sealing member). Furthermore, the sealing member may have a second flange portion that protrudes outward more than the flange portion. With this configuration, it is easier to apply force when removing the sealing member, and it can be easily removed.
[0017] Furthermore, the present invention can also be understood as a storage container, namely, a storage container for storing blood samples, having an internal space with one end open, in which a separating agent is held, and the thinnest part of the separation layer formed when 100 μL of blood sample is added to the internal space and centrifuged at a rotation speed of 3000 G using an angle rotor for 10 minutes is 0.50 mm or more in thickness, making it a micro-storage container.
[0018] With this configuration, the separation layer is more easily maintained even if some vibration occurs, and the breakdown of the separation state can be suppressed even when blood is separated using an angle rotor and then transported over long distances. Normally, trace samples are placed in containers at analytical laboratories and then subjected to centrifugation or analysis equipment, but the applicant is considering a new system in which the patient places the trace sample in the container and performs the centrifugation operation, and then transports it to the analytical laboratory. Assuming such transport, inexpensive angle rotors are likely to be used, and the separation layer is formed at an angle to the axial direction of the container, but since the container is upright during transport, pressure is easily applied to the separation layer during lateral vibrations. Therefore, the strength of the partition wall was investigated, and it was found that the separation layer can be transported without collapsing if the thinnest part of the separation layer is 0.50 mm or thicker. Furthermore, if the container has a narrow diameter region, it is preferable that a portion of the separation layer formed when 100 μL of a blood sample containing approximately 55% plasma components and approximately 45% blood cell components (average component ratios of human blood), respectively, is added to the internal space and centrifuged at 3000 G for 10 minutes using a 40-degree angle rotor, is located within the narrow diameter region. With such a configuration, in a container intended for a 100 μL blood sample, the components below the separation layer are more easily positioned within the narrow diameter region, and the liquid level is more easily raised. Also, if the internal space has a gently sloping section, it is preferable that a portion of the separation layer formed when 100 μL of a blood sample containing approximately 55% plasma components and approximately 45% blood cell components, respectively, is added to the internal space and centrifuged at 3000 G for 10 minutes using a 40-degree angle rotor, is in contact with the gently sloping section. With this configuration, in a container designed for a 100 μL blood sample, the separated upper layer is more likely to be located in a space with a larger inner diameter, allowing for efficient sample collection of the upper layer.
[0019] Further, the inner surface forming the internal space may be coated with a blood clot adhesion preventing agent. According to such a configuration, inversion of the separating agent and blood in the container is likely to occur, facilitating the formation of the separation layer. That is, when it is desired to increase the thickness of the separation layer or when forming the separation layer by an angle rotor, a large amount of the separating agent will be accommodated in the internal space. However, as the amount of the separating agent increases, it becomes more difficult for the sample to reach below the separating agent, and a situation may occur where the separation layer is not formed even after centrifugation. However, by coating the inner surface with a blood clot adhesion preventing agent, inversion of the separating agent and blood in the container is likely to occur, and the separation layer can be stably formed easily during centrifugation. Preferably, an annular rib protruding radially inward is formed on the inner surface forming the upper cylindrical portion below the sealing member. According to such a configuration, when applying the blood clot adhesion preventing agent and drying it by blowing, scattering of the agent to the outside can be suppressed, and formation of the separation layer can be facilitated by overall coating.
[0020] In the present invention, as much as possible, the means for solving the above problems can be combined and used.
Effect of the Invention
[0021] According to the present invention, it is possible to provide a storage container in which even a small amount of the sample extraction operation of the upper layer after separation is easy.
Brief Description of the Drawings
[0022] [Figure 1] FIG. 1A is a side view showing the appearance of a sample storage container in an embodiment of the present invention. FIG. 1B is an external view showing a state where the cap and the container body in an embodiment of the present invention are separated. FIG. 1C is an external view showing the lower space of the sample storage container in an embodiment of the present invention. [Figure 2] It is a cross-sectional view of a sample storage container in an embodiment of the present invention. [Figure 3] It is an explanatory view showing the inclination angles of the gentle inclination portion and the steep inclination portion of the sample storage container, and the small diameter region in an embodiment of the present invention. [Figure 4] This is a schematic diagram illustrating the structure of the cap portion in an embodiment of the present invention. [Figure 5] This is a schematic cross-sectional view showing the sample collection container in an embodiment of the present invention attached to a centrifuge. [Figure 6] This is a schematic diagram showing the state of the sample after centrifugation of the sample stored in the sample collection container in an embodiment of the present invention. [Modes for carrying out the invention]
[0023] The following describes embodiments of the present invention. The embodiments shown below are examples of embodiments of the present invention and do not limit the technical scope of the present invention to the following embodiments. For example, in the following examples, an example of collecting blood as a biological sample is described, but the biological sample is not limited to blood. The micro-storage container of the present invention preferably has a liquid storage space volume of 500 μL or less when the container body is sealed with a sealing member. The amount of biological sample preferably is 250 μL or less.
[0024] <Examples> Figures 1A to 1C show the external appearance of the sample storage container 1 according to this embodiment. The sample storage container 1 is a roughly cylindrical container for storing collected blood and for centrifuging the blood by attaching it to a centrifuge (not shown). Here, the blood is separated by centrifugation into blood cells (formed elements including cells such as red blood cells and white blood cells) and plasma (liquid components including serum, etc.). The sample storage container 1 in this embodiment is a small container for storing a small amount of blood (for example, about 100 μL), and for example, the total length can be about 27.8 mm, the outer diameter of the widest part can be 7.8 mm, and the volume of the liquid storage space can be about 400 μL.
[0025] Figure 1A is a front view showing the external appearance of the sample storage container 1. The rear view and each side view will have the same shape as the front view. The sample storage container 1 has a container body 3 as a storage member for storing the collected blood, and a cap 2 which is a lid that closes (seals) the container body 3 to prevent the blood from spilling out. Figure 1B shows the sample storage container 1 with the cap 2 and the container body 3 separated.
[0026] The container body 3 has a substantially cylindrical outer wall portion 31 in which an internal space (not shown in Figures 1A to C) that serves as the sample storage area is formed, and is configured to stand upright with the end opposite to the end sealed by the cap 2 as the bottom. In this specification, the side that becomes the bottom when standing upright will be described as the lower side, and the opposite side as the upper side. The means for making the container body 3 stand upright may be, for example, a configuration in which the outer diameter of the lower end of the container body 3 is larger than the inner diameter of the upper end of the container body 3. The internal space is open only at the top of the container body 3 and is sealed by the cap 2. Therefore, the opening is closed. The internal space will be explained in detail later.
[0027] Furthermore, as shown in Figure 1C, the container body 3 is also open at its lower end, and a lower space 39 is formed by the outer wall portion 31, the tapered wall portion 33, and the bottom portion 34, separate from the internal space described above. In addition, the container body 3 has a flange portion 32 that is convex in a flange shape above the central part in the longitudinal direction (axial direction), more specifically near the upper end.
[0028] The cap 2 is a flexible member that seals the opening (opening to the internal space) formed at the upper end of the container body 3. The cap 2 may be made of a flexible elastomer or polyethylene, for example. As shown in Figures 1A and 1B, the cap 2 is also provided with a cap flange portion 21 that is convex in a flange shape.
[0029] The cap flange portion 21 is configured to protrude outward more significantly than the main body flange portion 32. The main body flange portion 32 of the container body 3 functions as a stopper when installed in a centrifuge, as will be described later, and also serves to prevent the cap 2 from being pushed below the main body flange portion 32. When the container body 3 is properly sealed with the cap 2 (without applying excessive force), a small gap (for example, about 0.1 mm) is created between the cap flange portion 21 and the main body flange portion 32.
[0030] Next, the internal space 35 of the container body 3 will be described based on Figures 2 and 3. Figure 2 is a schematic cross-sectional view showing the aa section of Figure 1A. Figure 3 is an explanatory diagram showing the inclination angles of the gently sloping and steeply sloping sections, which will be described later, as well as the narrow diameter region N. As shown in Figure 2, the container body 3 has an internal space 35 that tapers downwards. The internal space 35 is a space formed by the outer wall portion 31 (the upper part) of the container body 3, a tapered wall portion 33 that branches off from the outer wall portion 31 towards the lower central portion (i.e., it moves further away from the outer wall portion 31 as it goes downwards), and a bottom portion 34 that is formed continuously with the tapered wall portion 33, and the collected blood is stored in this space. Note that the tapered portion formed by the tapered wall portion 33 that branches off from the outer wall portion 31 does not have a uniform inclination angle, but rather the inclination angle differs in stages. When the inclination angle of the tapered wall portion 33 changes, the tapered portion is smoothly connected before and after the change. More specifically, as shown in Figure 3, a gently sloping section is formed located in the axial middle of the internal space and has an inclination angle θ1 with respect to the direction perpendicular to the container body, and a steeply sloping section is formed below the gently sloping section and has an inclination angle θ2 with respect to the direction perpendicular to the container body that is steeper than that of the gently sloping section. In this embodiment, the inclination angle θ1 of the gently sloping section with respect to the direction perpendicular to the container body is formed at 69 degrees, but it is preferably 30 to 75 degrees, and more preferably 60 to 75 degrees. Also, in this embodiment, the inclination angle θ2 of the steeply sloping section with respect to the direction perpendicular to the container body is formed at 86 degrees, but it is preferably 80 to 90 degrees. The difference in inclination angles between the steeply sloping section and the gently sloping section is preferably 10 degrees or more, and more preferably 15 degrees or more. The steeply sloping section facilitates the formation of the narrow-diameter region described later, and makes it easier to position the liquid surface of the sample above the container. Furthermore, because the gently sloping section is located midway axially within the internal space (between the upper cylindrical section and the steeply sloping section), it is easier to position the upper layer of the sample in a space with a relatively large inner diameter, improving the operability of sampling with instruments such as pipettes. The steeply sloping section and the gently sloping section are smoothly connected so that the angle of inclination gradually decreases. Specifically, the gently sloping section is formed at an axial position that is half the axial length of the internal space. Specifically, the steeply sloping section is formed below an axial position that is half the axial length of the internal space.
[0031] The internal space 35 is divided into a sealed portion including the open end into which the sealing member is inserted, an upper cylindrical portion 35a with a substantially constant diameter formed by the upper part of the outer wall portion 31, and a lower cylindrical portion 35b located below the upper cylindrical portion 35a, connected to the upper cylindrical portion at a different angle, and having an inner diameter that decreases toward the lower end. The upper cylindrical portion 35a and the lower cylindrical portion 35b form a liquid containment space. The length of the lower cylindrical portion 35b is 50% or more of the length of the internal space 35 in the longitudinal direction (axial direction). That is, the length of the lower cylindrical portion is 50% or more of the length from the opening to the bottom surface located on the opposite side of the opening. The axial length of the upper cylindrical portion is formed to be longer than the axial length of the gently sloping portion. Here, "approximately constant diameter" means that the inner diameter of the entire portion is approximately constant, and in this embodiment, a slope (draft angle) is provided on the inner surface to improve mold release properties. In addition, the inner wall forming the internal space between the upper cylindrical portion 35a and the lower cylindrical portion 35b has a curved surface that is convex outward from the container, and the upper cylindrical portion 35a and the lower cylindrical portion 35b are smoothly connected. In addition, the inner wall forming the internal space between the gently sloping portion and the steeply sloping portion has a curved surface that is convex inward from the container, and the gently sloping portion and the steeply sloping portion are smoothly connected. With this configuration, blood components move smoothly during centrifugation, preventing blood components from remaining between inner surfaces with different angles, and improving separation accuracy.
[0032] As shown in Figure 3, the lower cylindrical portion 35b has a narrow-diameter region N whose inner diameter is less than or equal to half the inner diameter of the opening. That is, the narrow-diameter region N has a diameter of less than or equal to half the maximum diameter dimension in the internal space. The ratio of the axial dimension of the narrow-diameter region N to the longitudinal length (axial dimension) of the internal space is 30% or more, preferably 35% or more, and more preferably 40% or more. In this embodiment, it is set to 44.7%. In this embodiment, the narrow-diameter region N is formed at a position approximately half the axial length of the internal space from the bottom surface of the internal space.
[0033] The inner surface where the upper cylindrical portion 35a is formed may be provided with annular ribs that protrude radially inward. With this configuration, when applying a blood clot prevention agent such as silicone to the internal space and drying it by blowing, the scattering of the agent to the outside can be suppressed, and the overall coating facilitates the formation of a separation layer.
[0034] The internal space 35 is pre-filled with a separation agent 4 made of a material with a specific gravity lower than that of blood cell components but higher than that of plasma components. When the sample storage container 1 is upright, the separation agent 4 accumulates at the bottom of the lower cylindrical portion 35b formed by the tapered wall portion 33 and the bottom portion 34. The amount of separation agent 4 to be filled can be, for example, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, etc. However, if the amount relative to the volume is increased beyond a certain point, the separation agent may not separate from the bottom during centrifugation, resulting in a failure to form a separation layer. To address this, a blood clot adhesion prevention agent is applied to the internal space, making it easier for the separation agent to separate from the container and improving the likelihood of separation layer formation when a large amount of separation agent is filled. Although not shown in the figures, the inner surface of the internal space 35 of the sample storage container 1 in this embodiment is coated with other agents, such as coagulation accelerators, by methods such as spraying.
[0035] Furthermore, in the region opposite to the internal space 35, with the tapered wall portion 33 and the bottom portion 34 in between, a gap is formed between the outer wall and the tapered wall portion, creating a lower space 39 that opens downwards. Preferably, the upper end of the lower space is located radially outward of the gently sloping portion. If such a gap is not present and a lower space is not formed, the shape accuracy may decrease due to sink marks during molding, etc. If the upper end of the lower space is located radially outward of the steeply sloping portion, the volume of the narrow diameter region N will change due to sink marks during molding, etc., reducing the effect of obtaining bulk height. As shown in Figure 2, the bottom portion is located in a recessed area above the lower end of the container body 3, making it difficult for external forces to be applied to the bottom portion and reducing the risk of damage to the bottom portion.
[0036] Figure 4 shows the sealing structure by the cap 2, and is a schematic cross-sectional view of the vicinity of the upper opening of the container body 3 with the cap 2 attached. The cap 2 is made of an elastic material, and when attached to the container body 3, it deforms to conform to the shape of the container body 3, as shown by the colored shape in Figure 4. The cap 2 is attached to the opening of the container body 3 by pushing it in from the top to the bottom. When properly sealed, as shown in Figure 4, the cap is formed at three locations: the upper end of the outer wall portion 31, the inner circumferential surface, and the outer circumferential surface. The cap 2 and the container body 3 are in contact. Specifically, the cap 2 has an upper end contact portion 22 that contacts the upper end of the container body, an inner circumferential surface contact portion 23 that contacts the inner circumferential surface of the container body, and an outer circumferential surface contact portion 24 that contacts the outer circumferential surface of the container body. This sealing structure, which contacts at three points, ensures that the container body 3 is securely sealed. In addition, the inner circumferential surface contact portion 23 of the cap 2 has two annular protrusions extending outward in the outer direction, one at the top and one at the bottom. With this configuration, the protrusions can easily compress the inner circumferential surface of the container body, and the sealed state can be stably maintained. Furthermore, it is preferable that the sealing member also compresses the outer circumferential surface of the main body member in the radial direction. When transporting over long distances, there is concern about the movement of the sealing member due to vibration. If the inner surface of the main body member is slightly tapered, if the cap lifts, the compression state weakens, and the sealing performance against the inner surface of the main body member may weaken. However, because the outer surface of the main body member is also in a compressed state with the sealing member, even if a slight displacement occurs, it is possible to ensure that blood does not leak to the outside. Note that there are not necessarily two protrusions, but it is preferable that a part of the inner surface of the container body be a straight section with a constant diameter, and that the protrusions are in contact with the straight section. Furthermore, it is preferable that the compression region with the outer surface of the main body member is longer in the axial direction than the protrusions, which can stabilize the sealing performance in the event of cap lifting. It is also preferable that the compression by the protrusions is stronger than the compression with the outer surface of the main body member.
[0037] Figure 5 shows the sample storage container 1 in use. The sample storage container 1 is mounted on the rotor 5 of the centrifuge (angle rotor). More specifically, the rotor 5 has a circular mounting hole 51 into which the sample storage container 1 is inserted. When the sample storage container 1 is inserted into the mounting hole 51 of the rotor 5, the sample storage container 1 descends until the main body flange portion 32 contacts the edge of the mounting hole 51 on the surface of the rotor 5. In this embodiment, the centrifuge is a small model equipped with an angle rotor, and the most common angle rotor type centrifuge with a rotational inclination of 40 degrees to the horizontal plane was used.
[0038] When mounted, the rotor 5 and sample storage container 1 are tilted so that the lower side is closer to the outer circumference, as shown in the figure. In Figure 5, θ3 is defined as the angle between the rotor's rotation axis AX and the central axis C of the sample storage container 1 when mounted in the mounting hole 51. In this state, when the rotor 5 rotates around the rotation axis AX, centrifugal force acts on the blood stored in the internal space 35 of the sample storage container 1 in a direction perpendicular to the rotation axis AX. At this time, a stronger centrifugal force acts on the blood cell components in the blood because their specific gravity is higher than that of the plasma components. Also, since the specific gravity of the separation agent 4 is higher than that of the plasma components and lower than that of the blood cell components, only the blood cell components in the blood pass through the layer of separation agent 4 and aggregate in the lower cylindrical portion 35b of the internal space 35. On the other hand, the plasma components remain on the upper side of the separation agent 4 in the internal space 35.
[0039] Figure 6 shows the state of the sample in the sample storage container 1 after centrifugation. As shown in Figure 6, after centrifugation, the blood is separated into plasma 42 and blood cells 43, separated by a separation layer 41 containing a separation agent 4.
[0040] Furthermore, when centrifugation is performed using an angle rotor as in this embodiment, the separation layer 41 is formed at an angle to the central axis C of the sample storage container 1, as shown in Figure 6. That is, by collecting a small amount of blood and storing it in the sample storage container 1 according to this embodiment, and then performing centrifugation using an angle rotor to form a separation layer 41 that is inclined with respect to the longitudinal direction of the sample storage container 1, a portion with height (depth) is formed in the plasma 42 stored in the upper part of the internal space 35, and it is possible to enjoy the advantage that the plasma 42 can be easily extracted from this portion using instruments such as pipettes, droppers, and nozzles of the device.
[0041] Furthermore, when centrifuging a sample storage container 1 to which 100 μL of blood has been added, as in this embodiment, using an angle rotor, the lower end of the separation layer 41 is formed in the lower cylindrical portion 35b. Compared to the case where the lower end of the separation layer 41 is formed in the upper cylindrical portion 35a, the thickness of the separation layer increases, resulting in blood separation. The plasma 42 is positioned at the top, making it easier to extract the plasma 42.
[0042] In this embodiment, the thickness W of the separation layer 41 is the distance between the two end faces of the separation layer (separation surfaces from plasma 42 and blood cells 43, respectively) in a direction inclined at (90-θ3) degrees with respect to the central axis C of the sample storage container 1, as shown in Figure 6. Here, θ3 is the same as shown in Figure 5 (the angle between the rotation axis AX of the rotor and the central axis C of the sample storage container 1 when it is mounted in the mounting hole 51).
[0043] The thickness W can be measured, for example, based on a CT scan image of the sample storage container 1 with the separation layer 41 formed. When measured by this method, it is desirable that the thinnest part of the separation layer 41 has a thickness W of 0.50 mm or more. Preferably, the thickness W of the thinnest part of the separation layer 41 is formed within the range of 0.54 mm to 2.6 mm, and more preferably within the range of 1.19 mm to 2.58 mm.
[0044] <Example of experiment> In this embodiment, experiments were conducted on the separation layer 41 formed by varying the amount of separation agent 4 filled into the internal space 35 of the sample storage container 1. The volume of the internal space 35 of the sample storage container 1 is approximately 392 cm³. 3 Specifically, 100 μL of bovine blood was stored in each of the sample storage containers 1, each containing a different amount of separating agent 4 filling the internal space 35. This was then centrifuged at 3000 G for 10 minutes using an angle rotor type centrifuge (LACHOI, lch-mcf-1008d). Subsequently, each centrifuged sample was stored in sample storage container 1 and transported over a long distance (specifically, round-trip transport by truck between Shiga and Tokyo under refrigeration) to confirm the state of the separation layer 41.
[0045] Table 1 below shows the experimental results regarding the amount of separation agent 4 filled into the internal space 35, the thickness of the thinnest part of the separation layer 41 formed after centrifugation, the state of the separation layer 41 formed after centrifugation, and the state of the separation layer 41 confirmed after long-distance transport. The first row of Table 1 shows the amount of separation agent 4 filled into the internal space 35, the second row shows the thickness of the thinnest part of the formed separation layer 41, the third row shows the state of the separation layer 41 confirmed immediately after centrifugation, and the fourth row shows the state of the separation layer 41 confirmed after long-distance transport. A circle (○) indicates that the separation layer 41 has been formed and the plasma 42 and blood cells 43 have been separated.
[0046] [Table 1]
[0047] As shown in Table 1, when 10 mg, 40 mg, and 50 mg of the separating agent were packed and centrifuged, a separation layer 41 was formed, and plasma 42 and blood cells 43 were separated by the separating agent. The octopus separation layer 41 did not disintegrate even during long-distance transport, and the state in which the plasma 42 and blood cells 43 were separated was maintained.
[0048] According to the sample storage container 1 in this embodiment as described above, since the drug is held in the internal space where the blood is stored, the blood can be collected in the container and sealed, and then immediately placed in a centrifuge. Furthermore, since the container is designed to be self-supporting, it is easy to handle, and a sample storage container that is easy to use even in facilities that are not specialized institutions can be provided. In addition, by appropriately adjusting the amount of separation agent filled in the internal space of the sample storage container, even if the separation agent layer is formed at an angle when centrifugation is performed using an angle rotor, the sample can withstand the load of long-distance transport and be maintained in a separated state.
[0049] Furthermore, since a lower space 39 is formed in the container body 3, the tapered wall portion is covered by the outer wall. This reduces the likelihood of external force being applied to the tapered wall portion and damaging it. In addition, the cap flange portion 21 of the cap 2 protrudes outward more significantly than the main body flange portion 32, making it easier to apply force and facilitating the removal of the cap 2.
[0050] Furthermore, it is preferable that a portion of the separation layer formed when 100 μL of blood samples containing approximately 55% plasma components and approximately 45% blood cell components, respectively, are added to the internal space and centrifuged at 3000 G for 10 minutes using a 40-degree angle rotor, is located within the narrow-diameter region N. With this configuration, in a container intended for a 100 μL blood sample, the components below the separation layer are more likely to be located within the narrow-diameter region N, making it easier to raise the liquid level. Also, if the internal space has a gently sloping section, it is preferable that a portion of the separation layer formed when 100 μL of blood samples containing approximately 55% plasma components and approximately 45% blood cell components, respectively, are added to the internal space and centrifuged at 3000 G for 10 minutes using a 40-degree angle rotor, is in contact with the gently sloping section. With this configuration, in a container intended for a 100 μL blood sample, the separated upper layer is more likely to be located in the space with a larger inner diameter, allowing for efficient sampling of the upper layer. The average ratio of plasma components to blood cell components in human blood is said to be approximately 55% plasma and 45% blood cell components.
[0051] <Variation> The above embodiments are merely illustrative examples illustrating the present invention, and the present invention is not limited to the specific forms described above. The present invention can be modified in various ways within the scope of its technical concept. For example, in the above embodiments, the case of collecting blood as an example of a biological sample was described, but it is not limited to this. Also, in the above embodiments, the drug filled into the container body 3 was a separating agent, but since it is possible to separate the sample using a centrifuge without using a separating agent, a separating agent may not be necessary. For example, a blood anticoagulant, a coagulation accelerator, etc., may be filled or coated into the container body 3 to hold it. [Explanation of Symbols]
[0052] 1. Sample storage container 2. Cap 21...Cap flange section 22...Top end contact part 23...Inner peripheral surface contact part 24...Outer surface contact part 3. Container body 31...Outer wall 32. Main body flange section 33. Tapered wall section 34...bottom 35... Interior space 35a...Upper cylinder part 35b...Lower cylinder part 39...lower space 4. Separating agent 41...separation layer 42...plasma 43... Blood cells 5. Angle rotor (centrifuge) 51... Mounting holes AX... Rotor rotation axis N...Narrow diameter area W... thickness
Claims
1. A micro-storage container for storing liquid samples, It comprises a cylindrical main body member having an internal space that is open only at the top, and a sealing member that seals the opening, The internal space is divided into a sealed portion into which the sealing member is inserted, an upper cylindrical portion located below the sealed portion and forming a liquid containment space, and a lower cylindrical portion connected to the upper cylindrical portion at a different angle and having an inner diameter that decreases toward the lower end. A micro-storage container in which the axial length of the lower cylindrical portion is 50% or more of the axial length from the opening to the bottom surface of the internal space located on the opposite side of the opening.
2. The micro-storage container according to claim 1, wherein the main body member is integrally formed with the wall portion forming the internal space, and has an outer wall portion whose lower end is located lower than the lower cylindrical portion, and the outer wall portion is configured to be self-supporting with the lower end as the bottom.
3. The micro-storage container according to claim 2, wherein the lower cylindrical portion has a narrow diameter region having a diameter dimension of 1 / 2 or less of the maximum diameter dimension in the internal space, and the narrow diameter region extends in the axial direction such that it has an axial dimension of 30% or more of the axial length in the internal space.
4. The micro-storage container according to claim 3, wherein the lower cylindrical portion has a gently sloping portion located in the axial middle of the internal space and inclined with respect to the direction perpendicular to the axis, and a steeply sloping portion located below the gently sloping portion and inclined at a steeper angle than the gently sloping portion with respect to the direction perpendicular to the axis.
5. The micro-storage container according to claim 4, wherein the main body member is provided with a tapered wall portion that forms the lower cylindrical portion on the inside of the outer wall portion, and a gap is formed between the outer wall portion and the tapered wall portion.
6. The micro-storage container according to claim 5, wherein the bottom of the internal space is located above the lower end of the outer wall.
7. The micro-storage container according to claim 6, wherein the sealing member seals the opening of the main body member by contacting the outer and inner surfaces of the main body member.
8. The micro-storage container according to claim 3, wherein a separating agent is held in the internal space, and when 100 μL of blood sample is added to the internal space and centrifuged at a rotational speed of 3000 G using an angle rotor for 10 minutes, the thinnest part of the separation layer formed is 0.50 mm or more in thickness.
9. The micro-storage container according to claim 8, wherein the inner surface forming the internal space is coated with a blood clot adhesion prevention agent.
Citation Information
Patent Citations
Specimen collection and separation instrument
WO2016147748A1