Liquid dispensing device and filter media

Abstract

The present invention provides a liquid dispensing device and filter material that can obtain a suitable filtrate for measurement even from minute samples. [Solution] A liquid dispensing device comprising: a storage chamber configured to store liquid inside; a filter disposed in the storage chamber; a storage container for storing the filtrate after the liquid has passed through the filter; a flow path for guiding the filtrate from the storage chamber to the storage container; and a pressure loading mechanism for applying positive pressure to the liquid stored in the storage chamber, wherein the filter comprises a fiber filter and a resin filter disposed downstream of the fiber filter in the direction of liquid flow, and the resin filter is a porous body having multiple holes, and the holes have a sloping structure in which the diameter of the holes decreases toward the downstream side.

Description

Technical Field

[0001] The present invention relates to a liquid discharge device for filtering and collecting a small amount of liquid and a filter medium for filtering the liquid.

Background Art

[0002] When analyzing and measuring a biological sample, centrifugation or filter filtration is performed to remove contaminants and substances that interfere with the measurement contained therein. For example, when the biological sample is blood collected from a person, plasma or serum excluding the cell (blood cell) component in the blood is often used. This plasma or serum is obtained by centrifuging whole blood with a centrifuge to separate blood cells. In addition, various techniques for obtaining plasma or serum by filter filtration without using a centrifuge have been proposed.

[0003] As this filter filtration technique, a technique of using glass fiber filter paper or a combination of glass fiber filter paper and a resin porous membrane as a filter to filter blood is widely known (see, for example, Patent Documents 1 to 4).

[0004] To perform filter filtration, a container for collecting the filtered liquid (filtrate) is required. However, in order to improve the efficiency of the filtration operation and simplify the storage of the filtrate until the subsequent measurement operation, a blood filter provided with a receiving tank for storing the filtrate integrally or detachably has been proposed (see, for example, Patent Documents 4 to 8). These include a holder main body and a lid attached to the upper surface of the holder main body. The blood sucked from the blood inlet formed in the holder main body passes through the filter housed in the holder main body from below to above and reaches the upper surface of the filter while being filtered. Then, the filtrate on the upper surface of the filter is introduced into the receiving tank through a nozzle provided inside the lid. According to this, the filtrate can be easily stored without separately preparing a container for collecting and storing the filtrate.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Application Publication No. 9-196911 [Patent Document 2] Japanese Patent Publication No. 2003-43031 [Patent Document 3] Japanese Patent Publication No. 2006-38512 [Patent Document 4] Japanese Patent Application Publication No. 11-38002 [Patent Document 5] Japanese Patent Application Publication No. 10-185780 [Patent Document 6] Japanese Patent Publication No. 2000-180444 [Patent Document 7] Japanese Patent Publication No. 2008-232785 [Patent Document 8] Japanese Patent Publication No. 2019-49458 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] In recent years, there has been a trend towards further reducing the amount of sample collected from subjects in order to minimize the invasiveness and physical burden on patients and other subjects during sample collection. However, with filter filtration, some liquid remains in the filter medium, so as the amount of sample collected from subjects decreases, it becomes difficult to obtain the amount of filtrate necessary for measurement.

[0007] While it is possible to increase the volume of filtrate by applying an external force during filtration, such as pressure filtration or suction filtration, and by increasing the applied external force, this presents a problem: the solid components captured by the filter are more easily destroyed, potentially resulting in a filtrate unsuitable for measurement. For example, if the sample is whole blood, hemolysis is more likely to occur.

[0008] Furthermore, in order to discharge the liquid components held in the filter material from the filter, external pressure must be continuously applied, which in some cases increases the probability of air bubbles being introduced into the filtrate. Even if air bubbles (foaming) are present in the stored filtrate, it is generally not possible to easily add an antifoaming agent considering the impact on the measurement. However, since the amount of filtrate obtained from a small amount of sample is even smaller, if air bubbles remain, it is often difficult to eliminate the inclusion of air bubbles when dispensing the amount of filtrate required for measurement. Air bubbles in the measurement sample can lead to measurement errors, so if the measurement sample cannot be dispensed from the filtrate without air bubbles being introduced, it may affect the reliability of the measurement results.

[0009] The present invention provides a liquid dispensing device and filter material that can obtain a suitable filtrate for measurement even from a minute amount of sample. [Means for solving the problem]

[0010] The liquid dispensing device according to claim 1 comprises a storage chamber configured to store liquid inside, a filter disposed in the storage chamber, a storage container for storing the filtrate after the liquid has passed through the filter, a flow path for guiding the filtrate from the storage chamber to the storage container, and a pressure loading mechanism for applying positive pressure to the liquid stored in the storage chamber, wherein the filter comprises a fiber filter and a resin filter disposed downstream of the fiber filter along the direction of liquid flow, and the resin filter is a porous body having a plurality of holes, and the holes have a gradient structure in which the diameter of the holes decreases toward the downstream side.

[0011] In the liquid discharge device configured as described above, when pressure is applied to the liquid introduced into the storage chamber, filtration of the liquid through the filter is promoted, and the filtrate (the substance to be measured) can be injected from the storage chamber through the flow path into the storage container.

[0012] The liquid dispensing device according to claim 2 is characterized in that, in the liquid dispensing device according to claim 1, the resin filter is made up of multiple layers stacked together. In the liquid dispensing device configured as described above, the liquid to be filtered passes through a resin filter having a gradient structure two or more times.

[0013] The liquid dispensing device according to claim 3 is the liquid dispensing device according to claim 1 or 2, characterized in that the pressure loading mechanism is a piston fitted into the storage chamber and movably formed within the storage chamber. In the liquid dispensing device configured as described above, a piston applies pressure to the liquid stored in the storage chamber.

[0014] The liquid dispensing device according to claim 4 is a liquid dispensing device according to claim 1 or 2, further comprising a metering pin that is movable relative to the storage container while in contact with the wall surface of the storage container, wherein at least a portion of the flow path is formed in the metering pin, and a recess is formed in the contact surface where the metering pin and the wall surface of the storage container abut, with the recess extending toward the metering pin side or toward the storage container side, and the metering pin is configured to be movable between a first position in which the recess is open to the inside of the storage container, a second position in which a sealed space is formed by the recess and the wall surface of the storage container, and a third position in which the recess is open to the outside of the storage container. In the liquid dispensing device configured as described above, when moving from the first position through the second position to the third position, the filtrate stored in the storage container flows into the recess, and the filtrate, having a volume equal to the region of the recess formed on the contact surface between the metering pin and the wall of the storage container, moves from the inside to the outside of the storage container. This enables quantitative sampling of the filtrate.

[0015] The liquid dispensing device according to claim 5 is characterized in that, in the liquid dispensing device according to claim 4, the recess is formed on the side surface of the metering pin. In the liquid dispensing device configured as described above, liquid is introduced into a recess formed on the side of the metering pin, thereby sealing a predetermined volume of filtrate between the metering pin and the wall of the storage container and quantitatively collecting it.

[0016] The liquid ejection device according to claim 6 is the liquid ejection device according to claim 5, wherein when the depression of the metering pin moves from the first position to the third position via the second position, the liquid having the volume of the region surrounded by the depression and the wall surface of the storage container is configured to move from the inside to the outside of the storage container.

[0017] The liquid ejection device according to claim 7 is the liquid ejection device according to claim 5, wherein an upper end portion of the depression of the metering pin has an inclined portion whose diameter gradually decreases downward. In the liquid ejection device configured as described above, even when bubbles are entrapped in the depression of the metering pin when quantitatively collecting the filtrate, the bubbles escape upward due to the inclined portion at the upper end portion of the depression.

[0018] The liquid ejection device according to claim 8 is the liquid ejection device according to claim 7, wherein a lower end portion of the depression of the metering pin has an inclined portion whose diameter gradually increases downward. In the liquid ejection device configured as described above, the inclined portion at the lower end portion of the depression prevents the filtrate inside the depression from remaining in the depression.

[0019] The liquid ejection device according to claim 9 is the liquid ejection device according to claim 5, wherein the metering pin is inserted into a through hole formed in the bottom surface of the storage container, the metering pin is configured to be movable in the vertical direction through the through hole, and when the metering pin moves in the vertical direction through the through hole, the metering pin is configured to move between the first position, the second position, and the third position. In the liquid ejection device configured as described above, when the depression of the metering pin moves downward through the through hole from above, the filtrate stored in the storage container flows into the depression, and the filtrate having the volume of the region surrounded by the depression and the through hole moves from the inside to the outside of the storage container.

[0020] The liquid dispensing device according to claim 10 is the liquid dispensing device according to claim 9, wherein the storage container has a limiting portion that restricts the downward movement of the quantitative pin, and when the downward movement of the quantitative pin is restricted by the limiting portion, the upper end of the recess is located above the upper end of the through hole. In the liquid dispensing device configured as described above, when quantitative sampling of the filtrate is not performed, the quantitative pin is held in the storage container such that the recess of the quantitative pin is positioned above the upper end of the through-hole. In other words, the position of the quantitative pin is maintained with the filtrate from the storage container entering the recess of the quantitative pin.

[0021] The liquid dispensing device according to claim 11 is characterized in that, in the liquid dispensing device according to claim 10, the quantitative pin is configured to be switchable between a first state in which downward movement is restricted by the limiting portion and a second state in which downward movement is not restricted by the limiting portion. In the liquid dispensing device configured as described above, the quantitative pin is kept in the first state when quantitative sampling of the filtrate is not performed, and the quantitative pin is switched to the second state when quantitative sampling of the filtrate is performed.

[0022] The liquid dispensing device according to claim 12 is characterized in that, in the liquid dispensing device according to claim 10, it has a positioning unit that positions the quantitative pin in the first state. In the liquid dispensing device configured as described above, the quantitative pin is positioned in the first state when quantitative sampling of the filtrate is not performed.

[0023] The liquid dispensing device according to claim 13 is the liquid dispensing device according to claim 4, wherein the metering pin is configured to be rotatable relative to the storage container, and when the metering pin rotates relative to the storage container, the metering pin is configured to move between the first position, the second position, and the third position. In the liquid dispensing device configured as described above, when the metering pin rotates relative to the storage container, the filtrate stored in the storage container flows into the depression, and the filtrate, having a volume in the region enclosed by the depression and the storage container, moves from the inside to the outside of the storage container.

[0024] The liquid dispensing device according to claim 14 is a liquid dispensing device according to claim 3, characterized in that a cylindrical projection is formed on the bottom surface of the storage container, a communication hole is formed in the metering pin so as to penetrate the metering pin in the vertical direction, and the projection is configured to be inserted into the communication hole. In the liquid dispensing device configured as described above, the protrusion formed on the bottom surface of the storage container is inserted into the communication hole, thereby raising the water level of the filtrate flowing into the bottom surface of the storage container.

[0025] The liquid dispensing device according to claim 15 is characterized in that, in the liquid dispensing device according to claim 14, a gap is formed between the outer circumference of the protruding portion and the communication hole, and the outer circumference of the metering pin and the storage container are in contact. In the liquid dispensing device configured as described above, the filtrate that flows into the bottom of the storage container is introduced between the outer circumference of the protrusion and the communication hole without entering between the outer circumference of the metering pin and the storage container.

[0026] The liquid dispensing device according to claim 16 is characterized in that, in the liquid dispensing device according to claim 14, the outer circumference of the protruding portion and the communication hole are in contact, and a gap is formed between the outer circumference of the metering pin and the storage container. In the liquid dispensing device configured as described above, the filtrate that flows into the bottom of the storage container is introduced between the outer circumference of the metering pin and the storage container without entering the space between the outer circumference of the protrusion and the communication hole.

[0027] The liquid dispensing device according to claim 17 is characterized in that, in the liquid dispensing device according to claim 13, a discharge hole for discharging the liquid to the outside of the storage container is formed on the side surface of the storage container. In the liquid dispensing device configured as described above, the filtrate that flows into the bottom of the storage container is discharged to the outside of the storage container through a discharge hole formed on the side of the storage container.

[0028] The liquid dispensing device according to claim 18 is characterized in that, in the liquid dispensing device according to claim 17, the discharge hole is formed at the third position in a position that communicates with the recess. In the liquid dispensing device configured as described above, the discharge hole communicates with the recess at the third position, thereby discharging the filtrate to the outside of the storage container.

[0029] The liquid dispensing device according to claim 19 is characterized in that, in the liquid dispensing device according to claim 13, the recess is formed on the wall surface of the storage container. In the liquid dispensing device configured as described above, a predetermined volume of filtrate is sealed between the metering pin and the wall of the storage container by flowing the filtrate into a recess formed in the wall of the storage container, thereby enabling quantitative sampling.

[0030] The liquid dispensing device according to claim 20 is the liquid dispensing device according to claim 19, characterized in that a groove opening into the interior of the storage container is formed on the side surface of the metering pin, a discharge hole for communicating the liquid with the outside of the storage container is opened on the side surface of the metering pin at a position different from the position where the groove is formed in the circumferential direction of the metering pin, at the first position the recess is open to the interior of the storage container through the groove, and at the third position the recess is open to the outside of the storage container through the discharge hole. In the liquid dispensing device configured as described above, grooves and discharge holes are formed at different positions in the circumferential direction on the side surface of the metering pin. By rotating the metering pin relative to the storage container, the device switches between a position where the recess opens into the storage container through the groove and a position where the recess opens to the outside of the storage container through the discharge hole.

[0031] The filter material according to claim 21 comprises a fiber filter and a resin filter disposed downstream of the fiber filter in the direction of liquid flow, wherein the resin filter is a porous body having a plurality of pores, the pores have a gradient structure in which the pore diameter decreases toward the downstream side, and the resin filter is made up of multiple layers stacked together. The filter material according to claim 22 is characterized in that, in the filter material according to claim 21, the liquid to be filtered is blood. Therefore, plasma or serum is obtained by filtration. [Effects of the Invention]

[0032] According to the liquid dispensing device of the present invention, even with a small amount of liquid, a filtrate can be obtained with a good recovery rate, and the destruction of solid components excluded by filtration during the filtration process can be suppressed. As a result, an appropriate amount of sample in a suitable state can be obtained. Furthermore, according to the filter material of the present invention, if this filter material is used when, for example, a small amount of blood is pressure filtered, the destruction (hemolysis) of solids captured by the filter material can be suppressed while obtaining a filtrate with a good recovery rate. [Brief explanation of the drawing]

[0033] [Figure 1] This is a cross-sectional view showing the entire liquid dispensing device. [Figure 2] This is a perspective view showing the entire liquid dispensing device. [Figure 3] This is a perspective view of a storage container. [Figure 4] This is a cross-sectional view of the storage container taken along line AA in Figure 3. [Figure 5] This is a cross-sectional view of the storage container taken along line BB in Figure 3. [Figure 6] This is a perspective view of a syringe. [Figure 7] This is a cross-sectional view of the syringe cut along the CC line in Figure 6. [Figure 8] This is a magnified view of the filter in the syringe body. [Figure 9] This is a perspective view of the piston. [Figure 10] This is a cross-sectional view showing the state of the filtrate before quantitative sampling. [Figure 11] This is a perspective view showing the positional relationship between the storage container and the syringe in the state shown in Figure 10. [Figure 12] This is a cross-sectional view showing the process of quantitatively sampling the filtrate. [Figure 13] This is a perspective view showing the positional relationship between the storage container and the syringe in the state shown in Figure 12. [Figure 14] This is a cross-sectional view showing the state after quantitative sampling of the filtrate. [Figure 15] This is a perspective view showing another embodiment of the storage container and syringe. [Figure 16] This is a cross-sectional view showing another embodiment of the storage container and syringe. [Figure 17] This is a perspective view showing another embodiment of the storage container and syringe. [Figure 18] This is a cross-sectional view showing another embodiment of the storage container and syringe. [Figure 19] This is a cross-sectional view showing another embodiment of the storage container and syringe. [Figure 20] This is a cross-sectional view showing another embodiment of the storage container and syringe. [Figure 21] This figure shows another embodiment of the quantitative pin. [Figure 22] This figure shows another embodiment of the quantitative pin. [Figure 23] This figure shows another embodiment of the quantitative pin. [Figure 24] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 25] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 26] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 27] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 28] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 29] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 30] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 31] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 32] This is a cross-sectional view showing another embodiment of the liquid dispensing device. [Figure 33] This figure shows another embodiment of a storage container and syringe. [Figure 34] This figure shows another embodiment of a storage container and syringe. [Modes for carrying out the invention]

[0034] Embodiments of the present invention will be described below with reference to the drawings shown as an example. Figure 1 is a cross-sectional view showing the entire liquid dispensing device 1. Figure 2 is a perspective view showing the entire liquid dispensing device 1. The liquid dispensing device 1 is a device for quantitatively collecting filtrate. In this embodiment, a device for quantitatively collecting plasma after separating it from blood using a filter will be described as an example. In other words, in this embodiment, blood is used as the liquid and plasma as the filtrate. As shown in Figures 1 and 2, the liquid dispensing device 1 includes a storage container 10 for storing the filtrate before quantitative collection, a syringe 20 for injecting the filtrate into the storage container 10 and for quantitatively collecting the filtrate, a recovery tube 30 for collecting the quantitatively collected filtrate, a filter 40 for separating a part of the components of the liquid (blood) injected into the syringe 20, and a piston 50 for applying pressure to the liquid injected into the syringe 20.

[0035] Figure 3 is a perspective view of the storage container 10. The storage container 10 is made of resin or the like and has a cylindrical shape with an upward opening. The storage container 10 has a cylindrical container body 11, an inclined portion 12 whose diameter gradually decreases below the container body 11, a circular flange 13 extending outward from the upper end of the side surface of the container body 11, and a circular flange 14 extending outward from the side surface of the lower end of the inclined portion 12.

[0036] Figure 4 is a cross-sectional view of the storage container 10 taken along line AA in Figure 3. Figure 5 is a cross-sectional view of the storage container 10 taken along line BB in Figure 3. The container body 11 has a cylindrical liquid storage space inside. The inclined portion 12 is formed below the container body 11 and is continuous with the container body 11. The interior of the inclined portion 12 has a conical liquid storage space formed so that the diameter gradually decreases downwards. At the lower end of the inclined portion 12, a through hole 15 with a circular cross-section is formed so as to penetrate vertically through the bottom surface of the storage container 10. A circular opening 16 is formed at the upper end of the container body 11. Two notches 17 are formed inside the opening 16. The notches 17 have a rectangular cross-sectional shape in plan view and side view and are formed from the upper end of the container body 11 to a predetermined height position. In other words, the circular opening 16 has a rectangular shape that protrudes radially outward at the positions of the two notches 17 on the circumference. The two notches 17 are formed at opposite positions on the circumference of the opening 16, that is, 180° apart. Two projections 18 are formed at positions adjacent to each notch 17 in the circumferential direction, projecting upward from the upper surface of the container body 11. The projections 18 have a rectangular cross-sectional shape in both plan and side views. The projections 18 are formed only on one side of the notch 17 in the circumferential direction, and not on the other side. It can also be said that the inner wall on one side of the notch 17 extends vertically upward beyond the upper surface of the container body 11 (flange 13). Furthermore, a projection 19 is formed at a position midway between the two notches 17 (projections 18) in the circumferential direction (approximately 90° apart from the notches 17), projecting upward from the upper surface of the container body 11. The projections 19 have a rectangular cross-sectional shape in both plan and side views.

[0037] Figure 6 is a perspective view of the syringe 20. Figure 7 is a cross-sectional view of the syringe 20 taken along the CC line in Figure 6. The syringe 20 is made of resin or the like. The syringe 20 has a syringe body 21 with a cylindrical shape that opens upward, a cylindrical metering pin 22 that extends downward from the bottom surface of the syringe body 21, and a circular flange 23 that extends outward at the upper end of the syringe body 21. The metering pin 22 has a circular cross-sectional shape in plan view. The outer diameter of the metering pin 22 is formed to be approximately the same as (slightly smaller than) the inner diameter of the through hole 15 formed in the bottom surface of the storage container 10. The lower end of the metering pin 22 is inserted into the through hole 15 from above. The metering pin 22 is configured to be movable in the vertical direction within the through hole 15.

[0038] Two projections 24 are formed on the outer circumference of the syringe body 21, projecting outwards. The projections 24 have a rectangular cross-sectional shape in both plan and side views. The two projections 24 are formed on opposite sides of the circular opening 25 in a plan view, i.e., 180° apart. The external dimensions of the projections 24 are formed to be approximately the same as (slightly smaller than) the dimensions of the notch 17 formed on the inside of the container body 11 of the storage container 10. When the projections 24 are inserted into the notch 17, they are configured to slide vertically within the notch 17. This allows the syringe 20 to move vertically along the notch 17 relative to the storage container 10. Furthermore, when the projections 24 are positioned above the container body 11 (flange 13) of the storage container 10, the bottom surface of the projections 24 abuts against the top surface of the container body 11, allowing the syringe 20 to rotate horizontally on the container body 11.

[0039] A circular opening 25 is located at the upper end of the syringe body 21. The syringe body 21 is configured to allow liquid to be injected into the syringe 20 from above the opening 25. A circular communication hole 26 is formed in the center of the bottom surface of the syringe body 21. The communication hole 26 penetrates vertically through the center of the bottom surface of the syringe body 21 and diagonally crosses the metering pin 22, opening on the side of the metering pin 22. When liquid is injected into the syringe 20, the communication hole 26 functions as a liquid channel that guides the filtrate from the bottom surface of the syringe body 21 through the metering pin 22 to the storage container 10. As shown in Figure 1, a filter 40 is placed in the space below the opening 25 of the syringe body 21, and a piston 50 is placed above the filter 40. The space formed between the upper surface of the filter 40 and the lower surface of the piston 50 functions as a storage chamber 28 in which the liquid before filtration can be stored.

[0040] A recess 27 is formed on the side of the quantitative pin 22 below the exit of the communication hole 26. The recess 27 is a portion of the quantitative pin 22 whose volume is reduced by a predetermined volume compared to the case where the outer shape of the quantitative pin 22 was assumed to be a perfect cylinder. As will be described in detail later, when the recess 27 moves from top to bottom through the through hole 15 formed in the bottom surface of the storage container 10, the filtrate having a volume in the region enclosed by the recess 27 and the inner wall of the through hole 15 moves from the inside to the outside of the storage container 10. By designing the recess 27 to have a predetermined volume, filtrate of a predetermined volume can be moved from the storage container 10 to the recovery tube 30. The predetermined volume is, for example, 20 μl. As shown in the partially enlarged view of Figure 7, the upper end of the recess 27 has a linear inclined portion 27A in side view that gradually decreases in diameter toward the bottom. The lower end of the recess 27 has a linear inclined portion 27B in side view that gradually increases in diameter toward the bottom. Between the inclined portion 27A and the inclined portion 27B, an arc-shaped intermediate portion 27C is formed in a side view. The inclined portion 27A and the inclined portion 27B are inclined at an angle θ with respect to the vertical direction.

[0041] The recovery tube 30 has a cylindrical shape with an upward opening. The recovery tube 30 is positioned below the syringe 20. The upper end of the recovery tube 30 is detachably attached to the outside of the lower end of the storage container 10. When the filtrate is quantitatively collected by the syringe 20 with the recovery tube 30 attached to the storage container 10, the filtrate that flows out of the syringe 20 is collected by the recovery tube 30. The inside of the recovery tube 30 is pre-filled with a chemical solution, and the filtrate quantitatively collected by the syringe 20 and the chemical solution filled inside the recovery tube 30 are mixed inside the recovery tube 30. As shown in Figure 1, etc., a flange 31 extending outward is formed on the outer circumference of the recovery tube 30. When the liquid dispensing device 1 is placed on a rack or the like, the bottom surface of the flange 31 can support the liquid dispensing device 1.

[0042] A cylindrical filter 40 is positioned in the center of the bottom surface of the syringe body 21. The filter 40 is positioned to block the communication hole 26 on the bottom surface of the syringe body 21 from above. The liquid injected into the syringe 20 passes through the filter 40 before being introduced into the communication hole 26. The filter 40 is a device for separating a portion of the liquid's components (solids). By injecting the filtrate into the communication hole 26 via the filter 40, some of the components in the liquid remain in the filter 40 and are not introduced into the communication hole 26. In this embodiment, the filter 40 extracts only plasma from the blood, and the plasma is injected into the communication hole 26 as filtrate.

[0043] The internal volume of the syringe body 21 is sized to be suitable for filtering minute amounts of liquid. A minute amount is, for example, 80 μL to 2000 μL, sometimes 100 μL to 1000 μL, and preferably 150 μL to 500 μL. The internal volume of the syringe body 21 and the outer diameter (area) of the filter 40 are designed according to the liquid volume. For example, if the amount of liquid to be introduced is approximately 200 μL to 300 μL, the planar cross-sectional area of ​​the filter 40 should be 20 to 50 mm². 2 The inner diameter of the syringe body 21, the size of the communication hole 26, and the outer diameter of the filter 40 are specified so that the shape is approximately (for example, a circle with a diameter of 5 to 8 mm).

[0044] Figure 8 is an enlarged view of the filter 40 in a state where it is placed on the syringe body 21. The filter 40 comprises a fiber filter 40a and a resin filter 40b. The resin filter 40b is disposed on the bottom side of the syringe body 21, and the fiber filter 40a is disposed on the upper surface of the resin filter 40b. It can also be said that the resin filter 40b is positioned downstream of the fiber filter 40a in the direction of liquid flow. The fiber filter 40a is formed by intertwining fibers and molded into a sheet shape. This fiber filter 40a has voids (pores) between the intertwined fibers. The filter 40 may also be fixed inside the storage chamber 28 as appropriate. Existing fixing methods can be used, for example, ultrasonic welding, heat welding, fixing with adhesives such as hot melt adhesives and double-sided tape, and even fitting it inside the storage chamber using a sealing member, but are not limited to these.

[0045] When filtering blood, it is conceivable to use a filter that performs selective filtration on the surface of the filter material without allowing blood cells to pass through (a resin filter with a pore size smaller than that of blood cells). However, if such a filter is used without further consideration, blood cells will accumulate on the filter surface, causing clogging and preventing further filtration. Furthermore, if a strong external force is applied while the filter is clogged, the blood cells will be destroyed and hemolysis will occur. On the other hand, if the filter pore size is increased to prevent hemolysis, the blood cells will slip through the filter, resulting in poor filtration. Therefore, in this embodiment, a fiber filter 40a is provided as a pre-treatment filter in front of (upper side of) the resin filter 40b, which prevents the passage of solids based on the pore size.

[0046] The fiber filter 40a is designed to capture blood cells and reduce the number of blood cells that reach the resin filter 40b. Because the fiber filter 40a is formed by intertwining fibers, solid matter is captured by getting caught in the fibers. As a result, solid matter is captured from the permeating liquid not only on the surface but also in the thickness direction of the fiber filter 40a. In other words, blood cells are adsorbed and filtered throughout the entire filter material. By using such a fiber filter 40a, blood cells can be captured with varying degrees of density, and a corresponding amount of blood cells can be captured according to the filter volume, significantly reducing the amount of blood cells that reach the resin filter 40b. This suppresses congestion of blood cells in the resin filter 40b, and consequently suppresses the occurrence of hemolysis caused by this congestion.

[0047] Examples of fibers that make up the fiber filter 40a include glass fibers, resin fibers (e.g., polyolefin fibers, polyester fibers, polyamide fibers, etc.), and natural fibers (e.g., cotton, linen, silk, wool, etc.). Of these, a highly rigid fiber is selected that can form a filter in which the voids are not easily crushed even when pressure is applied to the liquid introduced into the syringe body 21. Glass fibers are preferred.

[0048] The fiber filter 40a has pore sizes (voids) that prevent clogging on its surface. A retained particle size of approximately 0.3 to 10 μm, particularly 0.5 to 5 μm, and even more preferably 0.6 to 3.5 μm, is preferred. The retained particle size represents the size of the retained particles and pore size, and in the case of the fiber filter 40a, it is an estimated value for particle retention performance. The fiber diameter has an average value of, for example, 2 μm or more and 10 μm or less, preferably 3 μm or more and 5 μm or less. This fiber diameter can be calculated by averaging the values ​​of 10 randomly measured fibers within the field of view under optical microscope observation, for each fiber recognized as a single fiber. The basis weight is, for example, 90 g / m². 2 More than 150g / m 2 Preferably 100 g / m 2 More than 140g / m 2The following applies: The thickness of the fiber filter 40a is, for example, 200 μm or more and 1000 μm or less, preferably 300 μm or more and 800 μm or less.

[0049] Various known methods can be applied to the manufacturing method of the fiber filter 40a. Examples of such methods include, but are not limited to, the dry method, wet method, spunbond method, thermal bond method, chemical bond method, stitch bond method, needle punch method, melt blow method, spunlace method, and steam jet method.

[0050] Since the volume of the fiber filter 40a is involved in the capture of blood cells, multiple fiber filters 40a are stacked and used as appropriate, depending on the amount of blood to be filtered and the amount of blood cells that can be captured per unit volume. The stacking thickness varies depending on the type of fiber filter 40a used, the filtration area, the amount of blood to be filtered, etc., but for example, it is 1 mm or more and 10 mm or less, preferably 1.8 mm or more and 6 mm or less.

[0051] When stacking fiber filters 40a, two or more identical filters may be stacked, or different filters may be stacked. By stacking multiple fiber filters 40a, a consistent effect can be obtained even when using filters with variations in pore size and retained particle size. Furthermore, when stacking different fiber filters 40a, it is desirable to place the filter with a smaller median void diameter at the bottom of the syringe body 21, and place the filter with a relatively larger median void diameter above it. Various commercially available fiber filters 40a can be used. An appropriate fiber filter 40a can be selected according to the amount of blood to be filtered, the pressure applied, the filtration area, etc.

[0052] As described above, in order to obtain the required amount of filtrate from a small amount of liquid, external pressure is applied to discharge the liquid held in the filter 40 from the filter 40. The filter 40 is configured to be suitable for pressurized filtration. The applied pressure is preferably positive and low, within the range that can secure the required amount of filtrate, for example, it may be 50 kPa or less, preferably 40 kPa or less, and more preferably 30 kPa or less. As described above, there is no particular lower limit to the applied pressure, but for example, it may be 10 kPa or more, and even more preferably 5 kPa or more.

[0053] When filtration is performed under external pressure, hemolysis is more likely to occur compared to filtration without external pressure. Therefore, as mentioned above, it is preferable that red blood cells are captured in a relatively dispersed state within the filter. Furthermore, it is desirable that filtration with the resin filter 40b is performed after most of the red blood cells have been removed by the fiber filter 40a.

[0054] A simple way to select an appropriate fiber filter 40a is to supply whole blood onto the fiber filter 40a and experimentally confirm that it is dark reddish-black in the thickness direction (entire area) of the filter. This confirms that it is suitable for volumetric filtration of whole blood. For example, if blood cells accumulate on the surface of the fiber filter, only the area near the surface will be colored, while if most of the blood cells pass through, there will be almost no coloring in the thickness direction, so such a fiber filter can be judged as unsuitable. Fiber filters can be selected simply through such a simple experiment.

[0055] When a glass fiber filter is used for the fiber filter 40a, the fiber filter 40a may be coated with a polymer material (including oligomers) to prevent protein adsorption to the glass fibers and component elution from the glass fibers. Examples of polymer materials used to coat the surface of the glass fibers include hydrocarbon resins, acrylate resins, amide resins, silicon resins, fluororesins, and polymer electrolytes. Specifically, examples of acrylate resins include polymethyl methacrylate (PMMA), polyhydroxyethyl methacrylate (PHEMA), and polymethoxyethyl acrylate (PMEA); examples of amide resins include polyamide 6, polyamide 12, and polyamide 66; and examples of hydrocarbon resins include polystyrene, but are not limited to these. Examples of silicon resins include polydimethylsiloxane, polyalkylphenylsiloxane, and modified silicon resins; and examples of fluororesins include polytetrafluoroethylene and tetrafluoroethylene-perfluoroalkyl vinyl ether copolymers, but are not limited to these.

[0056] As polymer electrolytes, those with dissociating groups in their repeating units are the most common. Common natural polymer electrolytes include pectin (polygalacturonic acid), alginates (alginic acid), and carboxymethylcellulose. Common synthetic polymer electrolytes include those with anionic groups such as carboxylates, phosphonates, and sulfonates, such as acrylic acid resins, polystyrene sulfonic acid resins, polystyrene sulfinic acid resins, and their salts, as well as those with cationic groups such as primary, secondary, and quaternary ammonium compounds, such as polyallylamine resins, polyvinylpyrimidine resins, and polyethyleneimine resins. Specifically, examples of anionic polymer electrolytes include sodium polyacrylate and sodium polystyrene sulfonate, and examples of cationic polymer electrolytes include polydiallyldimethylammonium chloride, but are not limited to these.

[0057] Furthermore, conventional polymer coating methods such as immersion, coating, and spraying can be used to coat the surface of the glass fibers with polymer materials. Specifically, methods such as immersing the glass fiber filter paper in a polymer solution or spraying the polymer solution onto the glass fiber filter paper, as described later, are possible, but immersing the glass fiber filter paper in a polymer solution is preferred in that it uniformly coats the surface of the glass fibers.

[0058] Furthermore, the glass fibers may be cleaned with acid before coating the surface of the glass fibers with a polymer material. Organic acids are particularly preferred as the acid used. It is preferable that the surface of the fiber filter 40a be hydrophilic. For this reason, the fiber filter 40a may be coated with a hydrophilic polymer material, or a hydrophilization treatment may be performed on the fiber filter 40a coated with a polymer material or on the fiber filter 40a itself. Examples of hydrophilization methods include, but are not limited to, hydrophilization by corona treatment or plasma treatment.

[0059] The resin filter 40b is a porous body having open pores, and has a gradient structure in which the cross-sectional area of ​​the pores in the planar direction gradually decreases in diameter from the surface to the back surface (from upstream to downstream). It suppresses the permeation of blood cells even more effectively than the fiber filter 40a. Preferably, two or more of these resin filters 40b are used in stacked form. In this case, the liquid to be filtered passes through the gradient structure two or more times. The material of the resin filter 40b can be, for example, epoxy resin, polycarbonate resin, nitrocellulose resin, cellulose acetate resin, nylon resin, polysulfone resin, fluororesin, etc. Preferably, it is polysulfone resin, cellulose acetate resin, etc., and particularly preferably polysulfone resin.

[0060] The resin filter 40b has numerous openings formed on its front and back surfaces, and also has a gradient structure in the thickness direction, resulting in a significant difference in pore size between the front and back surfaces. In other words, the pore size in the filter thickness direction has a wide distribution. There are no particular restrictions on the openings on the front side, as long as the pore size is large enough for blood cells to enter. On the other hand, most of the openings on the back side have a pore size that prevents blood cells from passing through.

[0061] The diameter of the pores in the back surface opening does not necessarily need to be smaller than that of red blood cells, as long as red blood cells cannot pass through, but it is preferable that it be smaller than the general outer diameter of red blood cells. On the other hand, considering fluid resistance, a larger pore diameter is preferable. Specifically, the pore diameter is, for example, 0.10 μm or more and 13.00 μm or less, preferably 0.50 μm or more and 12.00 μm or less, and even more preferably 0.80 μm or more and 11.00 μm or less.

[0062] Figure 9 is a perspective view of the piston 50. The piston 50 is positioned above the syringe 20 and functions as a pressure loading mechanism that applies positive pressure to the liquid stored in the storage chamber 28. The piston 50 has a piston body 51 inserted inside the syringe body 21 of the syringe 20, a flat plate portion 52 that can be pressed from above, a cylindrical shaft 53 connecting the piston body 51 and the flat plate portion 52, and an engaging portion 54 that engages with the flange 23 of the syringe 20. The piston body 51 has a circular outer shape in plan view. The outer diameter of the piston body 51 is formed to be approximately the same as (slightly smaller than) the inner diameter of the syringe body 21 of the syringe 20. The flat plate portion 52 is roughly circular in plan view and has a larger outer shape in plan view than the storage container 10 and the syringe 20. The engaging portion 54 has a vertical portion 54A that extends vertically downward from the bottom surface of the flat plate portion 52 and a claw portion 54B that extends radially inward from the lower end of the vertical portion 54A. The claw portion 54B has a flat surface on the upper side and an inclined portion on the lower side. The inclined portion is gradually inclined upward toward the radially inward side. When the piston 50 is pressed downward toward the flange 23, force is applied to the inclined portion, causing the engaging portion 54 to elastically deform radially outward, and the flange 23 engages between the flat plate portion 52 and the engaging portion 54.

[0063] The operation of each component when quantitatively sampling the filtrate using the liquid dispensing device 1 will be explained below with reference to Figures 10 to 14. Figure 10 is a cross-sectional view showing the state before quantitative sampling of the filtrate, and Figure 11 is a perspective view showing the positional relationship between the storage container 10 and the syringe 20 in that state. Figure 12 is a cross-sectional view showing the state during quantitative sampling of the filtrate, and Figure 13 is a perspective view showing the positional relationship between the storage container 10 and the syringe 20 in that state. Figure 14 is a cross-sectional view showing the state after quantitative sampling of the filtrate.

[0064] In the state shown in Figures 10 and 11, the bottom surface of the projection 24 that protrudes outward from the syringe body 21 of the syringe 20 is positioned on the upper surface of the container body 11 (flange 13) of the storage container 10. At this time, the side surface of the projection 24 is in contact with the side surface of the projection 19 that protrudes upward from the container body 11, as shown in Figure 11. Because the projection 24 and projection 19 are in contact, the syringe 20 cannot rotate any further counterclockwise from the state shown in Figure 11. In other words, the projection 19 positions the syringe 20 horizontally relative to the storage container 10. In this state, even if the syringe 20 is pressed downward against the storage container 10, the downward movement of the syringe 20 (metering pin 22) is restricted because the bottom surface of the projection 24 is in contact with the upper surface of the container body 11. The state of the syringe 20 (metering pin 22) when its downward movement is restricted is called the first state.

[0065] With the downward movement of the syringe 20 restricted (first state), liquid is injected into the syringe 20 from above. After injecting the liquid, the piston body 51 of the piston 50 is placed on the upper opening 25 of the syringe body 21, and a downward force is applied to the syringe body 21 from above (flat plate portion 52) of the piston 50. The engagement portion 54 of the piston 50 elastically deforms, causing the flange 23 to lock between the flat plate portion 52 and the engagement portion 54. Figures 10 and 11 show the state in which the flange 23 is locked between the flat plate portion 52 and the engagement portion 54. As the piston 50 is fixed to the syringe 20 in a downward-pressurized state, a sealed space is formed between the bottom surface of the piston body 51 and the inner wall of the syringe body 21, pressurizing the liquid injected into the syringe 20. This facilitates the liquid's passage through the filter 40. At this time, the downward movement of the syringe 20 is restricted by the projection 24, so even if a downward force is applied to the syringe 20 from the piston 50, the syringe 20 will not move downward relative to the storage container 10. The liquid (filtrate) that has passed through the filter 40 is discharged to the outside of the syringe 20 through the communication hole 26 via the inside of the syringe body 21. The outlet of the communication hole 26 is formed on the side of the metering pin 22, and since the metering pin 22 is inserted into the container body 11 of the storage container 10, the filtrate discharged from the communication hole 26 is injected into the container body 11 and stored inside the container body 11. When the syringe 20 is in the first state, the upper end of the recess 27 formed below the metering pin 22 is located above the upper end of the through hole 15 of the storage container 10. Also, the lower end of the recess 27 is located above the lower end of the through hole 15 of the storage container 10. Furthermore, the upper end of the recess 27 is located below the liquid level of the filtrate stored in the container body 11 of the storage container 10. In other words, the recess 27 is open to the inside of the storage container 10. The position of the syringe 20 relative to the storage container 10 at this time is called the first position.

[0066] Figures 12 and 13 show the state after the cylinder 20 has been rotated relative to the storage container 10 from the state shown in Figures 10 and 11. After the filtrate has been stored in the storage container 10, the syringe 20 is rotated approximately 90° horizontally (clockwise in Figure 13) relative to the storage container 10. By rotating the cylinder 20, the projection 24 that was in contact with projection 19 moves away from projection 19 and comes into contact with projection 18. When projection 24 comes into contact with projection 18, projection 24 is positioned to overlap with the notch 17 in a plan view. In this state, projection 24 does not interfere with the upper surface of the container body 11, so it becomes possible to move the syringe 20 downward relative to the storage container 10. When the syringe 20 moves downward relative to the storage container 10, the filtrate that has flowed into the recess 27 of the metering pin 22 is surrounded by the recess 27 and the inner wall of the through hole 15 in the state shown in Figure 12. In other words, a sealed space is formed when the recess 27 and the inner wall surface of the through-hole 15 of the storage container 10 come into contact, and the filtrate having the same volume as this sealed space is sealed. The position of the syringe 20 relative to the storage container 10 at this time is called the second position.

[0067] When the syringe 20 is moved further downward relative to the storage container 10 from the state shown in Figures 12 and 13, the bottom surface of the projection 24 comes into contact with the bottom surface of the notch 17. Figure 14 shows the state in which the bottom surface of the projection 24 comes into contact with the bottom surface of the notch 17. When the bottom surface of the projection 24 comes into contact with the bottom surface of the notch 17, the lower end of the inclined portion 27B of the recess 27 is located below the lower end of the through hole 15 formed in the storage container 10. As a result, the area enclosed by the recess 27 and the inner wall of the through hole 15 is opened downward, and the filtrate that was sealed between the recess 27 and the inner wall of the through hole 15 is injected into the recovery tube 30. In other words, the recess 27 is open to the outside of the storage container 10. The position of the syringe 20 relative to the storage container 10 at this time is called the third position. Since the syringe 20 is moved downward while the filtrate is sealed, the filtrate is discharged toward the recovery tube 30. As a result, the filtrate having the volume of the region enclosed by the recess 27 and the inner wall of the through hole 15 is moved from the storage container 10 to the recovery tube 30. The state of the syringe 20 (metering pin 22) when the projection 24 overlaps with the notch 17 and the downward movement of the syringe 20 (metering pin 22) is not restricted is called the second state.

[0068] As described above, in the liquid dispensing device 1 of the present invention, when the quantitative pin 22 moves from top to bottom while in contact with the wall surface of the through hole 15 of the storage container 10, and the recess 27 moves from the first position to the third position via the second position, the filtrate having the volume of the region enclosed by the recess 27 and the through hole 15 can be moved from the inside to the outside of the storage container 10. By setting the recess 27 to a predetermined volume, the syringe 20 is moved downward while the filtrate is sealed, so that the filtrate of a predetermined volume can be dispensed and quantitatively collected. By forming an inclined portion 27A at the upper end of the recess 27, even if air bubbles are trapped in the recess 27, the air bubbles can be released upward. Furthermore, by forming an inclined portion 27B at the lower end of the recess 27, the downward discharge of the filtrate into the recess 27 can be further promoted. In other words, by adopting the above configuration, the filtrate can be quantitatively collected with high accuracy. The projection 24 of the syringe 20 contacts the upper surface of the container body 11 of the storage container 10, thereby functioning as a limiting part that restricts the downward movement of the metering pin 22 (syringe 20). When the downward movement of the metering pin 22 is restricted (when quantitative sampling of filtrate is not performed), the upper end of the recess 27 is positioned above the upper end of the through hole 15, so that the filtrate stored in the storage container 10 flows into the area enclosed by the recess 27 and the inner wall of the through hole 15. The state of the metering pin 22 can be switched between a first state in which the projection 24 of the metering pin 22 contacts the upper surface of the flange 13 and restricts the downward movement of the metering pin 22, and a second state in which the projection 24 of the metering pin 22 overlaps with the notch 17 and the downward movement of the metering pin 22 is not restricted. This allows the quantitative pin 22 to be switched to a first state when injecting the filtrate into the storage container 10 or when applying pressure to the liquid with the piston 50, and to be switched to a second state only when quantitatively sampling the filtrate. The projection 19 formed on the upper surface of the container body 11 functions as a positioning part that positions the quantitative pin 22 in the first state. When quantitative sampling of the filtrate is not performed, the projection 19 can be used to position the quantitative pin 22 in the first state. Even when pressure is applied to the liquid with the piston 50 while the downward movement of the quantitative pin 22 is restricted, the syringe 20 can be prevented from moving downward relative to the storage container 10.

[0069] Figure 15 is a perspective view showing another embodiment of the storage container and syringe, and Figure 16 is a cross-sectional view. In this embodiment, the only differences from the above-described embodiment are that the storage container 10 has been changed to a storage container 110, the syringe 20 has been changed to a syringe 120, and a spacer 130 has been added. The other configurations are the same as those of the above-described embodiment. Below, only the differences from the above-described embodiment will be explained. The storage container 110 differs from the storage container 10 only in that it does not have the notches 17, protrusions 18 and 19. The syringe 120 differs from the syringe 20 only in that it does not have the protrusions 24. In this embodiment, instead of forming the notches 17, protrusions 18, protrusions 19 and 24, a spacer 130 separate from the storage container 110 and syringe 120 is provided. Figure 15 shows the spacer 130 removed from the syringe 120, and Figure 16 shows the spacer 130 attached to the syringe 120. The spacer 130 is preferably made of a flexible material such as resin. The spacer 130 has an annular gripping portion 131 with a cavity in the center, an annular spacer body 132 with a cavity in the center and a part cut out, and a connecting portion 133 that connects the gripping portion 131 and the spacer body 132. The spacer body 132 has an inner diameter that is approximately the same as (slightly larger than) the outer diameter of the syringe body 121 of the syringe 120. By elastically deforming the cut-out portion of the spacer body 132 to spread it outward, the spacer body 132 can be attached to and detached from the outer circumference of the syringe body 121. When the spacer body 132 is attached to the outer circumference of the syringe body 121, the spacer body 132 fills the vertical space between the storage container 110 and the syringe 120, as shown in Figure 16. In other words, if you try to move the syringe 120 downward relative to the storage container 110 from the state shown in Figure 16, the spacer 130 interferes between the storage container 110 and the syringe 120, restricting the downward movement of the syringe 120. As described above, in this embodiment, the spacer 130 functions as a limiting part that restricts the downward movement of the metering pin. When the spacer 130 is attached to the syringe 120, the syringe 120 enters a first state in which its downward movement is restricted by the limiting part.Furthermore, when the spacer 130 is removed from the syringe 120, the syringe 120 enters a second state in which its downward movement is not restricted by the limiting part. The device is configured to allow switching between the first and second states by attaching and detaching the spacer 130.

[0070] Figure 17 is a perspective view showing yet another embodiment of the storage container and syringe, and Figures 18, 19, and 20 are cross-sectional views. In this embodiment, the only differences from the above-described embodiment are that the storage container 10 has been changed to a storage container 210 and the syringe 20 has been changed to a syringe 220; the other configurations are the same as those of the above-described embodiment. Below, only the differences from the above-described embodiment will be explained. Compared to the storage container 10, the storage container 210 differs in that it does not have a notch 17 and a projection 19, and has a flange 211 that has a different shape from the flange 13. Compared to the syringe 20, the syringe 220 differs in that it does not have a projection 24, and at the upper end of the syringe 220, it has a projection 221 that protrudes downward from the bottom surface of a circular flange 223 that extends outward, and an engaging portion 222 is formed at the lower end of the projection 221. The flange 211 of the storage container 210 has an arc-shaped cross-section in a side view, as shown in Figure 18, etc. The projections 221 are formed at two locations on the bottom surface of the flange 223, separated by 180°. The engaging portion 222 has a bottom surface 222A configured to abut against the top surface of the flange 211 of the storage container 210, a top surface 222B configured to abut against the bottom surface of the flange 211 of the storage container 210, and a connecting surface 222C that connects the bottom surface 222A and the top surface 222B with an arc-shaped curved surface. The projections 221 and the engaging portion 222 are preferably made of a flexible material such as resin. In the state shown in Figures 17 and 18, the bottom surface 222A of the engaging portion 222 of the syringe 220 is in contact with the top surface of the storage container 210, and in this state, the downward movement of the syringe 220 is restricted. When the syringe 220 is pressed downward with a force greater than a certain amount, the projection 221 and the engaging portion 222 elastically deform, and the connecting surface 222C of the engaging portion 222 overcomes the arc-shaped side surface of the flange 211 of the storage container 210. As a result, as shown in Figure 19, the upper surface 222B of the engaging portion 222 comes into contact with the bottom surface of the flange 211. In this state, the syringe 220 can descend until the bottom surface of the flange 223 comes into contact with the top surface of the storage container 210. Figure 20 shows the state in which the bottom surface of the flange 223 of the syringe 220 comes into contact with the top surface of the storage container 210. As described above, in this embodiment, the projection 221 and the engaging portion 222 function as limiting parts that restrict the downward movement of the metering pin.When the engaging portion 222 of the syringe 220 comes into contact with the upper surface of the storage container 210, the syringe 220 enters a first state in which its downward movement is restricted by the limiting portion. When the engaging portion 222 moves over the side surface of the flange 211, the syringe 220 enters a second state in which its downward movement is not restricted by the limiting portion. The first and second states can be switched by engaging or disengaging the engaging portion 222 with the flange 223.

[0071] Figures 21 to 23 show another embodiment of the quantitative pin. The quantitative pin 322 shown in Figure 21 has a recess 327. The recess 327 is formed in an arc shape in a side view from the upper end to the lower end. The quantitative pin 422 shown in Figure 22 has a recess 427. The recess 427 is formed in an arc shape in a side view from the upper end to the lower end. Furthermore, unlike recesses 27 and 327, the recess 427 is formed so that its diameter decreases over the entire circumference of the quantitative pin 422. The recess 427 has the same cross-sectional shape regardless of where it is cut when cut vertically along a line passing through the center of the quantitative pin 422. The quantitative pin 522 shown in Figure 23 has a recess 527. The upper end of the recess 527 has a linear inclined portion 527A in a side view where the diameter gradually decreases downwards, and the lower end of the recess 527 has a linear inclined portion 527B in a side view where the diameter gradually increases downwards. Between the inclined portion 527A and the inclined portion 527B, an arc-shaped intermediate portion 527C is formed in a side view. Also, similar to the recess 427, the recess 527 has the same cross-sectional shape regardless of the position at which it is cut when cut vertically along a line passing through the center of the quantitative pin 522.

[0072] Figures 24 to 28 are cross-sectional views showing another embodiment of the liquid dispensing device. The liquid dispensing device 600 in this embodiment comprises a storage container 610, a syringe 620, a recovery tube 630, a filter 640, and a piston 650. The syringe 620 has a syringe body 621 with a cylindrical shape that opens upward and a cylindrical metering pin 622 that extends downward from the bottom surface of the syringe body 621. The recovery tube 630, filter 640, and piston 650 differ in shape from the recovery tube 30, filter 40, and piston 50, but have the same function, so their description is omitted. The storage container 610 differs from the storage container 10 in the following respects. The storage container 610 does not have a through hole formed on its bottom surface, and a cylindrical projection 611 is formed that protrudes upward from the bottom surface. In addition, a discharge hole 612 for discharging filtrate to the outside is provided on the side surface of the storage container 610. Syringe 620 differs from syringe 20 in the following respects: A communication hole 623 for discharging the liquid injected into the syringe body 621 to the storage container 610 is formed so as to penetrate vertically through the center of the metering pin 622. In addition, a communication hole 624 is formed in the metering pin 622, which penetrates the side wall surface of the metering pin 622 from the communication hole 623 and communicates with the outside of syringe 620. Furthermore, when syringe 620 is moved downward relative to the storage container 610, syringe 620 is configured to be rotatable relative to the storage container 610.

[0073] The operation of each component when quantitatively sampling filtrate using the liquid dispensing device 600 will be explained below, with reference to Figures 24 to 28, focusing on the differences from the liquid dispensing device 1. Figure 24 is a cross-sectional view showing the state before quantitative sampling of filtrate. In the state shown in Figure 24, the syringe 620 is restricted from moving downward relative to the storage container 610. In this state, after injecting liquid into the syringe body 621 from above, the piston 650 is placed on the syringe body 621, and a downward force is applied to the piston 650 from above. As a result, the liquid passes through the filter 640, is discharged downward from the syringe 620 via the communication hole 623, and is introduced into the storage container 610. A protrusion 611 is located directly below the communication hole 623, and the filtrate is stored at the bottom of the storage container 610 around the protrusion 611. After introducing the filtrate from the syringe 620 into the storage container 610, the syringe 620 is rotated horizontally relative to the storage container 610. This allows the syringe 620 to move downward relative to the storage container 610. Figure 25 shows the syringe 620 in the downward position. In the state shown in Figure 25, the protrusion 611 of the storage container 610 is inserted into the communication hole 623 of the syringe 620. Here, the inner diameter of the communication hole 623 is formed to be slightly larger than the outer diameter of the protrusion 611, and a gap is formed between the protrusion 611 and the communication hole 623 through which filtrate can flow. On the other hand, the outer diameter of the metering pin 622 and the inner diameter of the lower end of the storage container 610 are formed to be almost the same, and the outer circumference of the metering pin 622 is in contact with the storage container 610, and the filtrate is not allowed to flow between the outer circumference of the metering pin 622 and the storage container 610. As the protrusion 611 is inserted into the communication hole 623, the filtrate flows between the outer circumference of the protrusion 611 and the inner circumference of the communication hole 623 of the metering pin 622, as shown by the arrow in the blowout in Figure 25, and the water level gradually rises. Figure 26 shows the syringe 620 moved downward until the lower end of the metering pin 622 contacts the bottom surface of the storage container 610. As shown by the arrow in the blowout in Figure 26, the filtrate flows out of the metering pin 622 through the communication hole 624 from the communication hole 623. A recess 625 is formed on the outer circumference of the metering pin 622, and the filtrate flows between the recess 625 and the storage container 610. In this state, the recess 625 can be said to be open to the inside of the storage container 610.In other words, the position of the syringe 620 relative to the storage container 610 at this time is the first position.

[0074] After the recess 625 is filled with filtrate, the syringe 620 is rotated horizontally relative to the storage container 610. The recess 625 is not formed around the entire circumference of the metering pin 622, but only on a portion of it. Also, the wall surface of the storage container 610 has a radial gap between it and the metering pin 622 at the rotation position shown in Figure 26, but is configured to be in close contact with the metering pin 622 at the position shown in Figure 27. When the syringe 620 is rotated to a predetermined angle, it moves to a position where the recess 625 is hidden at the rear, as shown in Figure 27. At this time, the filtrate that has flowed into the recess 625 is sealed by the recess 625 and the wall surface of the storage container 610. In other words, a sealed space is formed by the recess 625 and the inner wall surface of the storage container 610, and filtrate with the same volume as the volume of this sealed space is sealed. The position of the syringe 620 relative to the storage container 610 at this time is the second position. If the syringe 620 is rotated further from the state shown in Figure 27, the recess 625 will be in a position to communicate with the discharge hole 612 formed in the storage container 610, as shown in Figure 28. As a result, the area enclosed by the recess 625 and the inner wall of the storage container 610 will be opened to the side, and the filtrate will be injected into the recovery tube 630. In other words, the recess 625 is open to the outside of the storage container 610. The position of the syringe 620 relative to the storage container 610 at this time is the third position. At this time, the lower end of the discharge hole 612 is located below the lower end of the recess 625. As described above, with the liquid dispensing device 600, by rotating the syringe 620 horizontally relative to the storage container 610 while it is in contact with the storage container 610, a predetermined volume of filtrate can be dispensed and quantitatively collected, similar to the storage container 10.

[0075] Figures 29 to 32 are cross-sectional views showing another embodiment of the liquid dispensing device. The liquid dispensing device 700 in this embodiment comprises a storage container 710, a syringe 720, a recovery tube 730, a filter 740, and a piston 750. The syringe 720 has a syringe body 721 with a cylindrical shape that opens upward and a cylindrical metering pin 722 that extends downward from the bottom surface of the syringe body 721. The recovery tube 730, filter 740, and piston 750 differ in shape from the recovery tube 30, filter 40, and piston 50, but have the same function, so their description is omitted. The storage container 710 differs from the storage container 10 in the following respects. The storage container 710 does not have a through hole formed on its bottom surface, and a cylindrical projection 711 is formed that protrudes upward from the bottom surface. In addition, a discharge hole 712 for discharging filtrate to the outside is provided on the side surface of the storage container 710. Syringe 720 differs from syringe 20 in the following respects: A communication hole 723 for discharging the filtrate injected into the syringe body 721 to the storage container 710 is formed so as to penetrate vertically through the center of the metering pin 722. In addition, when syringe 720 is moved downward relative to the storage container 710, syringe 720 is configured to be rotatable relative to the storage container 710.

[0076] The operation of each component when quantitatively sampling filtrate using the liquid dispensing device 700 will be explained below, with reference to Figures 29 to 32, focusing on the differences from the liquid dispensing device 1. Figure 29 is a cross-sectional view showing the state before quantitative sampling of filtrate. In the state shown in Figure 29, the syringe 720 is restricted from moving downward relative to the storage container 710. In this state, after injecting liquid into the syringe body 721 from above, the piston 750 is placed on the syringe body 721, and a downward force is applied to the piston 750 from above. As a result, the liquid passes through the filter 740, is discharged downward from the syringe 720 via the communication hole 723, and is introduced into the storage container 710. A protrusion 711 is located directly below the communication hole 723, and the filtrate is stored at the bottom of the storage container 710 around the protrusion 711. After introducing the filtrate from the syringe 720 into the storage container 710, the syringe 720 is rotated horizontally relative to the storage container 710. This allows the syringe 720 to move downward relative to the storage container 710. Figure 30 shows the syringe 720 in the downward position. In the state shown in Figure 30, the protrusion 711 of the storage container 710 is inserted into the communication hole 723 of the syringe 720. Here, the inner diameter of the communication hole 723 and the outer diameter of the protrusion 711 are formed to be almost the same (the inner circumference of the communication hole 723 and the outer circumference of the protrusion 711 are in contact), and the system is configured so that filtrate does not flow between the protrusion 711 and the communication hole 723. On the other hand, a gap is formed between the outer circumference of the metering pin 722 and the inner wall of the lower end of the storage container 710. As the protrusion 711 is inserted into the communication hole 723, filtrate flows between the outer circumference of the metering pin 722 and the inner wall of the lower end of the storage container 710, as shown by the arrow in the blowout in Figure 30, and the water level gradually rises. A recess 724 is formed on the outer circumference of the quantitative pin 722, and the filtrate flows between the recess 724 and the storage container 710. In this state, the recess 724 can be said to be open to the inside of the storage container 710. In other words, the position of the syringe 720 relative to the storage container 710 at this time is the first position.

[0077] After the recess 724 is filled with filtrate, the syringe 720 is rotated horizontally relative to the storage container 710. The recess 724 is not formed around the entire circumference of the metering pin 722, but only on a portion of it. Also, the wall surface of the storage container 710 has a radial gap between it and the metering pin 722 at the rotation position shown in Figure 30, but is configured to be in close contact with the metering pin 722 at the position shown in Figure 31. When the syringe 720 is rotated to a predetermined angle, it moves to a position where the recess 724 is hidden at the rear, as shown in Figure 31. At this time, the filtrate that has flowed into the recess 724 is sealed by the recess 724 and the wall surface of the storage container 710. In other words, a sealed space is formed by the recess 724 and the inner wall surface of the storage container 710, and the filtrate having the same volume as this sealed space is sealed. The position of the syringe 720 relative to the storage container 710 at this time is the second position. If the syringe 720 is rotated further from the state shown in Figure 31, the recess 724 will be in a position to communicate with the discharge hole 712 formed in the storage container 710, as shown in Figure 32. As a result, the area enclosed by the recess 724 and the inner wall of the storage container 710 will be opened to the side, and the filtrate will be injected into the recovery tube 730. In other words, the recess 724 is open to the outside of the storage container 710. At this time, the position of the syringe 720 relative to the storage container 710 is the third position. At this time, the lower end of the discharge hole 712 is located below the lower end of the recess 724. As described above, with the liquid dispensing device 700, by rotating the syringe 720 horizontally while it is in contact with the storage container 710, a predetermined volume of filtrate can be dispensed and quantitatively collected, similar to the storage container 10.

[0078] Figure 33 is a plan view and a cross-sectional view taken along the DD line showing another embodiment of the storage container and syringe (metering pin). Figure 34 is a plan view and a cross-sectional view taken along the EE line showing the syringe from Figure 33 rotated relative to the storage container. The storage container 810 and syringe 820 in this embodiment differ from previous embodiments in that the recess is formed on the wall surface of the storage container 810 rather than on the syringe 820. A through-hole 811 with a circular cross-sectional shape is formed so as to penetrate vertically through the bottom surface of the storage container 810. A recess 812 is formed on the inner wall of the through-hole 811, recessed toward the outside (storage container side). The recess 812 is a portion that increases the volume of the through-hole 811 by a predetermined volume compared to the case where the inner wall of the through-hole 811 was assumed to be a perfect cylinder. The syringe 820 is inserted into the through-hole 811 so as to abut against the inner wall of the through-hole 811. The syringe 820 is configured to be rotatable and movable vertically relative to the storage container 810. A groove 821 is formed on the side of the syringe 820 at a predetermined position in the circumferential direction. The groove 821 has an arc-shaped cross-section when viewed from above. The groove 821 opens into the interior of the storage container 810 at the top and extends to a predetermined position in the vertical direction. A discharge hole 822 is formed on the side of the syringe 820 at a position different from the groove 821 in the circumferential direction. The opening of the discharge hole 822 is located at the opposite position (180° apart) from the groove 821 in the circumferential direction. The discharge hole 822 has an L-shape when viewed in cross-section, extends horizontally inward from the side of the syringe 820, and extends downward from the center of the syringe 820 to communicate with the outside of the storage container 810.

[0079] In the state shown in Figure 33, the groove 821 is positioned to communicate with the recess 812. The filtrate injected into the storage container 810 flows into the recess 812 via the groove 821. In this state, the recess 812 can be said to be open to the inside of the storage container 810 via the groove 821. In other words, the position of the syringe 820 relative to the storage container 810 at this time is the first position. After the recess 812 is filled with filtrate, when the syringe 820 is rotated by a predetermined angle, the recess 812 is positioned so that it does not communicate with either the groove 821 or the discharge hole 822. In other words, a sealed space is formed by the recess 812 and the outer wall surface of the syringe 820, and the filtrate having the same volume as this sealed space is sealed. The position of the syringe 820 relative to the storage container 810 at this time is the second position. When the syringe 820 is rotated further, as shown in Figure 34, the recess 812 is positioned to communicate with the discharge hole 822. As a result, the area enclosed by the recess 812 and the outer wall surface of the syringe 820 is open to the outside of the storage container 810 through the discharge hole 822. In this state, the filtrate flows out to the outside of the storage container 810 through the discharge hole 822. The position of the syringe 820 relative to the storage container 810 at this time is the third position. As described above, by rotating the syringe 820 horizontally while it is in contact with the storage container 810, a predetermined volume of filtrate can be discharged and quantitatively collected, similar to the storage container 10.

[0080] In the above embodiment, plasma was used as an example of filtrate, but the filtrate is not limited to plasma. For example, the present invention can be applied when quantitatively collecting filtrate from various liquids such as pharmaceuticals, chemicals, and beverages. Furthermore, although an example of separating blood cells from blood using a filter has been described, the invention is not limited to this. It can also be used as a filter to separate specific components from liquids other than blood. In addition, the liquid dispensing device can be configured without using a piston.

[0081] In the above embodiment, a configuration in which a quantitative pin 22 is formed at the tip of the syringe 20 was described, but the present invention is not limited to such a configuration. Other structures are not particularly limited as long as the structure involves moving a quantitative pin that has a recess formed in it relative to the storage container. For example, it is also possible to have a structure in which the quantitative pin is directly installed relative to the storage container without providing a syringe. In that case, for example, a limiting part such as a protrusion is formed on the quantitative pin, and the downward movement of the quantitative pin relative to the storage container is restricted by bringing the limiting part of the quantitative pin into contact with the storage container.

[0082] In the above embodiment, recesses 27, 327, 427, and 527 were given as examples of the shape of the recesses of the quantitative pin, but the shape of the recesses is not limited to these. Even when the entire recess is formed in an arc shape, as in recesses 327 and 427, the upper end of the recess may have a sloping portion where the diameter gradually decreases downwards, and the lower end of the recess may have a sloping portion where the diameter gradually increases downwards. Recesses 427 and 527 were formed so that they have the same shape regardless of where they are cut in the vertical direction, but the shape may differ depending on the cutting position. It is also possible to form the recess by dividing it into multiple parts. In any case, the recesses should be formed so that the total volume of the recesses equals a predetermined volume. The volumes of the recesses described in the embodiment are also merely examples.

[0083] In the above embodiment, the projection 24 of the syringe 20, the spacer 130, the projection 221 of the syringe 220, and the engaging portion 222 were exemplified as limiting parts that restrict the downward movement of the quantitative pin. However, the structure of the limiting part is not limited to the structure described above. As long as the structure can restrict the downward movement of the quantitative pin, it is possible to adopt a structure other than the above as the limiting part.

[0084] In the above embodiment, a projection 19 is exemplified as a positioning part for positioning the quantitative pin in a first state, but the structure of the positioning part is not limited to a projection 19. As long as the structure positions the quantitative pin in a first state, it is possible to use a structure other than the above as the positioning part. The spacer 130 and projection 221 function as both a limiting part and a positioning part. It is also possible to use a structure in which claws or the like are provided on the positioning part to fix the quantitative pin so that it does not move from the first state.

[0085] In the above embodiment, an example was described in which the filtrate quantitatively collected with the quantitative pin 22 is collected in the collection tube 30, but the present invention is not limited to this. The collection tube 30 can be omitted, and the filtrate can be collected using a structure other than a collection tube. Furthermore, an example was described in which the collection tube 30 is pre-filled with a chemical solution and the collected filtrate and the chemical solution are mixed inside the collection tube, but mixing the collected filtrate with the chemical solution, that is, pre-filling the collection tube 30 with the chemical solution, is not essential.

[0086] In the above embodiment, embodiments were described in which a recess is formed on the side surface of the quantitative pin (syringe) and in which a recess is formed on the inner wall of the through-hole of the storage container into which the quantitative pin is inserted. In other words, a recess is formed on the contact surface where the side surface of the quantitative pin and the wall surface of the storage container come into contact, and the recess is recessed toward the quantitative pin or the storage container. By moving the recess from a position where it is open to the inside of the storage container, through a sealed position, to a position where it is open to the outside of the storage container, a filtrate of a predetermined volume can be discharged and quantitatively collected.

[0087] It goes without saying that the present invention is not limited to the embodiments described above. It goes without saying that those skilled in the art will understand this, - Applying the mutually interchangeable members and configurations disclosed in the above embodiments by appropriately changing their combinations. • Although not disclosed in the above embodiments, it is possible to appropriately substitute and apply known components and components that are mutually interchangeable with those disclosed in the above embodiments, by changing their combinations. • Although not disclosed in the above embodiments, the members and components that a person skilled in the art could conceive of as substitutes for the members and components disclosed in the above embodiments based on prior art, etc., may be appropriately substituted, and their combinations may be modified and applied. This is disclosed as one embodiment of the present invention. [Examples]

[0088] The present invention will be further described in detail by the following examples, but the present invention is not limited to these examples.

[0089] (Method for evaluating filtration performance) A plastic container was prepared, which had a bottomed cylindrical body with a through hole formed in the center of its base, and a protruding cylindrical outlet connected to the through hole, and the filter was placed inside it.

[0090] Furthermore, a pressurized sealed container with an openable and closable design was prepared, and the aforementioned plastic container was placed inside it. The pressurized sealed container is designed to be pressurized with compressed air, and a pressure gauge is connected to measure the pressure. In addition, a holding section is provided inside the pressurized sealed container to hold the plastic container, and the contained plastic container is held with its outlet facing downwards. After introducing blood onto the filter from above the plastic container, the pressurized sealed container was sealed and pressurized to perform pressurized filtration, and the filtered filtrate was collected to evaluate the filter performance.

[0091] Furthermore, a vacuum-sealed container configured to allow for pressure reduction was prepared. A pressure gauge for measuring pressure was connected to this container. In addition, a holding section for holding a plastic container was provided in the internal space, and the contained plastic container was held with its outlet facing downwards. After introducing blood onto the filter from above the plastic container, the vacuum-sealed container was sealed, the pressure was reduced, and suction filtration was performed. The filtered filtrate was collected and the filter performance was evaluated.

[0092] The fiber filter and resin filter were punched out into circles of a predetermined size using a leather punch. Then, the resin filter and fiber filter, each punched out to cover the through-hole in the bottom (for example, 7 mm in diameter), were layered in that order onto the plastic container. The layered filters were properly secured to prevent them from floating.

[0093] A glass fiber filter was used for the fiber filter. The glass fiber filter is primarily intended for volumetric filtration (depth filter), and when whole blood is filtered through the fiber filter, red blood cells are captured by becoming entangled in the fibers. On the other hand, the resin filter selectively filters red blood cells according to the pore size, and has open pores to trap solid matter depending on whether or not it can pass through the open pores. A polysulfone resin membrane with a gradient structure in which the opening diameter gradually decreases from the front to the back surface was used.

[0094] The bottom layer of the resin filter was secured to the bottom of the plastic container by appropriately attaching donut-shaped pieces of double-sided tape (outer diameter 7 mm, inner diameter 5 mm) to the underside of the bottom layer of resin filter, with the inner diameter ring being larger than the through-hole. Since liquid does not permeate the areas where the double-sided tape is attached, the diameter of the filter when the resin filter is secured using double-sided tape is the inner diameter of the donut-shaped double-sided tape.

[0095] (Example 1) The above plastic container contains a glass fiber filter (particle size retention 2.7~3.0 μm, basis weight 133~138 g / m²). 2Six glass fiber filters and two resin filters (thickness 330±20μm, back surface aperture diameter approximately 0.8~3.5μm) were stacked (total thickness approximately 5mm), and placed in a pressurized sealed container. 200μL of whole blood was supplied onto the glass fiber filter and pressure filtration was performed at a pressure of 30kPa. The aperture diameter on the back surface of the resin filter was measured randomly at 20 locations within the field of view under an optical microscope. The basis weight was determined by measuring the weight of the punched-out filter. The filtrate (plasma) collected in the recovery container was visually assessed for the degree of hemolysis (presence or absence) and blood cell permeability, and the plasma volume was measured. The results are shown in Table 1. (Example 2) The test was conducted in the same manner as in Example 1, except that the number of layers of resin filter was changed to three. The results are shown in Table 1. (Comparative Example 1) The test was conducted in the same manner as in Example 1, except that the number of layers of resin filter was set to one. The results are shown in Table 1. [Table 1]

[0096] As can be seen from Table 1, the filter material with a filter configuration consisting of multiple layers of resin filters showed a tendency to suppress hemolysis and also suppress the permeation of blood cells. In other words, even with a very small amount of blood sample as 200 μL, it was shown that by using this filter configuration, it is possible to obtain several tens of μL of filtrate (plasma) of appropriate quality for measurement. Furthermore, it was shown that the amount of plasma recovered can be further improved by pre-treating the glass fiber filter with a polymer to make it hydrophilic (data not shown).

[0097] (Examples 3-5) Except for not using adhesive tape to attach the resin filter, pressurized filtration was performed according to the filtration performance evaluation method described above. Since adhesive tape was not used, in Examples 3 to 5, the outer diameter of the resin filter (a circle with a diameter of 7 mm) became the filter diameter. The pressurized pressures were 30 kPa, 20 kPa, and 10 kPa. Other details were the same as in Example 1. The degree of hemolysis (presence or absence) in the filtrate (plasma) obtained by pressurized filtration was visually determined, and the plasma volume was measured. The test was performed multiple times. The results are shown in Table 2. (Comparative Example 4 to Comparative Example 6) The tests were conducted according to the filtration performance evaluation method described above, except that adhesive tape was not used to attach the resin filter. Since adhesive tape was not used, in Comparative Examples 4 to 6, the outer diameter of the resin filter (a circle with a diameter of 7 mm) became the filter diameter. In addition, in Comparative Examples 4 to 6, a vacuum-sealed container was used instead of a pressurized sealed container, and vacuum filtration was performed. The negative pressures applied were 30 kPa, 20 kPa, and 10 kPa. Other than that, the same procedure as in Example 1 was followed. The degree of hemolysis (presence or absence) of the recovered filtrate (plasma) was visually determined, and the plasma volume was measured. The test was performed multiple times. The results are shown in Table 2.

[0098] As can be seen from Table 2, when negative pressure was applied, clear hemolysis was observed under all conditions, indicating that hemolysis was more likely to occur with negative pressure than with pressure filtration. Furthermore, reducing the suction pressure did not improve hemolysis, and the amount of filtrate recovered was significantly reduced (Table 2 shows the minimum and maximum recovered amounts). In addition, a tendency to generate air bubbles during filtration was observed. From this, it was shown that pressure filtration is more useful than suction filtration when filtering whole blood. [Table 2]

[0099] (Examples 6, 7) Except for not using adhesive tape to attach the resin filter, pressurized filtration was performed according to the filtration performance evaluation method described above. Since adhesive tape was not used, in Examples 6 and 7, the outer diameter of the resin filter (a circle with a diameter of 7 mm) became the filter diameter. Other aspects were the same as in Example 1. The degree of hemolysis in the filtrate (plasma) obtained by pressurized filtration was visually assessed, and the plasma volume was measured. The test was performed multiple times. The results are shown in Table 3.

[0100] (Comparative Example 5) The tests were conducted according to the filtration performance evaluation method described above, except that adhesive tape was not used to attach the resin filter. Since adhesive tape was not used, in Comparative Example 5, the outer diameter of the resin filter (a circle with a diameter of 7 mm) became the filter diameter. The tests were conducted in the same manner as in Example 1, except that the number of layers of resin filter was one. The degree of hemolysis in the recovered filtrate (plasma) was visually determined, and the plasma volume was measured. The tests were performed multiple times. The results are shown in Table 3.

[0101] Regarding the degree of hemolysis, samples showing clear hemolysis were rated "×", samples showing visible hemolysis were rated "△", and samples where no hemolysis was visible were rated "〇". As can be seen from Table 3, it was shown that by using a filter configuration combining a fiber filter and a resin filter and performing pressurized filtration at the appropriate pressure, a sufficient amount of plasma (e.g., 20 μL or more) can be recovered even from a small amount of blood (in Table 3, the recovered amounts are the minimum and maximum recoverable amounts). When the amount of plasma recovered is large, even if some air bubbles are mixed in, it is possible to collect the appropriate amount (required amount) of sample by avoiding the air bubbles present on the liquid surface, and the effect of the mixed air bubbles can be ignored.

[0102] Furthermore, it was shown that, given the same total thickness of fiber filters, a configuration with multiple layers of resin filters tended to improve the degree of hemolysis. Therefore, when performing tests (measurements) that are more sensitive to (greatly affected by) hemolysis, increasing the total thickness of the fiber filters and layering these fiber filters on top of multiple layers of resin filters during blood filtration can yield plasma samples with sufficiently suppressed hemolysis, suitable for such tests. [Table 3] [Explanation of Symbols]

[0103] 1...Liquid dispensing device, 10...Storage container, 11...Container body, 12...Inclined section, 13...Flange, 14...Flange, 15...Through hole, 16...Opening, 17...Notch, 18...Protrusion, 19...Protrusion, 20...Syringe, 21...Syringe body, 22...Measuring pin, 23...Flange, 24...Protrusion, 25...Opening, 26...Communication hole, 27...Recess, 28...Storage chamber, 30...Recovery tube, 31...Flange, 40...Filter, 40a...Fiber filter, 40b...Resin filter Ruta, 50...piston, 51...piston body, 52...flat plate part, 53...shaft, 54...engaging part, 110...storage container, 120...syringe, 121...syringe body, 130...spacer, 131...gripping part, 132...spacer body, 133...connecting part, 210...storage container, 211...flange, 220...syringe, 221...projection, 222...engaging part, 322...metering pin, 327...recess, 422...metering pin, 427...recess, 522...metering pin, 527...recess.

Claims

1. A storage chamber configured to store liquid inside, A filter installed in the aforementioned storage chamber, A storage container for storing the filtrate after the liquid has passed through the filter, A channel for guiding the filtrate from the storage chamber to the storage container, The system includes a pressure loading mechanism that applies positive pressure to the liquid stored in the storage chamber, The filter comprises a fiber filter and a resin filter positioned downstream of the fiber filter along the direction of liquid flow. The aforementioned resin filter is a porous body having multiple pores, The liquid dispensing device is characterized in that the hole has a sloping structure in which the hole diameter decreases toward the downstream side.

2. The liquid dispensing device according to claim 1, characterized in that the resin filter is made up of multiple layers stacked together.

3. The liquid dispensing device according to claim 1 or 2, characterized in that the pressure loading mechanism is a piston fitted into the storage chamber and movably formed within the storage chamber.

4. The storage container is further equipped with a quantitative pin that is movable relative to the storage container while in contact with the wall surface of the storage container, At least a portion of the flow path is formed in the quantitative pin, A recess is formed in the contact surface where the quantitative pin and the wall surface of the storage container come into contact, with the recess extending toward either the quantitative pin side or the storage container side. The liquid dispensing device according to claim 1 or 2, characterized in that the quantitative pin is configured to be movable between a first position in which the recess opens into the interior of the storage container, a second position in which a sealed space is formed by the recess and the wall surface of the storage container, and a third position in which the recess opens to the outside of the storage container.

5. The liquid dispensing device according to claim 4, characterized in that the recess is formed on the side surface of the quantitative pin.

6. The liquid dispensing device according to claim 5, characterized in that when the recess of the quantitative pin moves from a first position through a second position to the third position, the liquid having a volume in the region enclosed by the recess and the wall surface of the storage container moves from the inside to the outside of the storage container.

7. The liquid dispensing device according to claim 5, characterized in that the upper end of the recess of the quantitative pin has an inclined portion whose diameter gradually decreases downward.

8. The liquid dispensing device according to claim 7, characterized in that the lower end of the recess of the quantitative pin has an inclined portion whose diameter gradually increases downward.

9. The quantitative pin is inserted into a through hole formed in the bottom surface of the storage container. The quantitative pin is configured to be movable vertically through the through hole. The liquid dispensing device according to claim 5, characterized in that the metering pin is configured to move between the first position, the second position and the third position when the metering pin moves vertically through the through hole.

10. The storage container has a limiting portion that restricts the downward movement of the quantitative pin. The liquid dispensing device according to claim 9, characterized in that when the downward movement of the quantitative pin is restricted by the limiting portion, the upper end of the recess is positioned above the upper end of the through hole.

11. The liquid dispensing device according to claim 10, characterized in that the quantitative pin is configured to be switchable between a first state in which downward movement is restricted by the limiting portion and a second state in which downward movement is not restricted by the limiting portion.

12. The liquid dispensing device according to claim 11, having a positioning unit for positioning the quantitative pin in the first state.

13. The quantitative pin is configured to be rotatable relative to the storage container. The liquid dispensing device according to claim 4, characterized in that the metering pin is configured to move between the first position, the second position and the third position when the metering pin rotates relative to the storage container.

14. A cylindrical projection is formed on the bottom surface of the storage container, projecting upward. The quantitative pin has a communication hole formed to penetrate the quantitative pin in the vertical direction. The liquid dispensing device according to claim 13, characterized in that the protruding portion is configured to be inserted into the communication hole.

15. A gap is formed between the outer circumference of the protruding portion and the communication hole. The liquid dispensing device according to claim 14, characterized in that the outer circumference of the quantitative pin and the storage container are in contact.

16. The outer circumference of the protruding portion and the communication hole are in contact with each other. The liquid dispensing device according to claim 14, characterized in that a gap is formed between the outer circumference of the quantitative pin and the storage container.

17. The liquid dispensing device according to claim 13, characterized in that a discharge hole for discharging the liquid to the outside of the storage container is formed on the side surface of the storage container.

18. The liquid dispensing device according to claim 17, characterized in that the discharge hole is formed at the third position in a position that communicates with the recess.

19. The liquid dispensing device according to claim 13, characterized in that the recess is formed on the wall surface of the storage container.

20. A groove is formed on the side of the quantitative pin, which opens into the inside of the storage container. On the side surface of the quantitative pin, a discharge hole is opened at a position different from the position where the groove is formed in the circumferential direction of the quantitative pin, allowing the liquid to communicate with the outside of the storage container. At the first position, the recess is open to the inside of the storage container via the groove, The liquid dispensing device according to claim 19, characterized in that, at the third position, the recess is open to the outside of the storage container through the discharge hole.

21. It comprises a fiber filter and a resin filter positioned downstream of the fiber filter along the direction of liquid flow, The aforementioned resin filter is a porous body having multiple pores, The hole has a gradient structure in which the hole diameter decreases toward the downstream side. The aforementioned resin filter is characterized by being made up of multiple layers stacked together.

22. The filter material according to claim 21, characterized in that the liquid is blood.

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