Density gradient liquid preparation device, density gradient liquid preparation method, particle size distribution measurement system and particle size distribution measurement method

Abstract

This density gradient liquid preparation apparatus is for preparing a density gradient liquid composed of a predetermined solution in a measurement cell for a centrifugal sedimentation-type particle size distribution measurement device, wherein the solution is supplied from an injection port such that the density thereof increases stepwise or continuously while the injection port for injecting the solution is positioned at the bottom of the measurement cell placed at a predetermined position.

Description

[Technical field]

[0001] The present invention relates to a density gradient liquid preparation device and a density gradient liquid preparation method for preparing a density gradient liquid in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, and a particle size distribution measurement system and a particle size distribution measurement method using these. [Background technology]

[0002] In the line start method using a centrifugal sedimentation type particle size distribution measurement device, a measurement sample is poured into a sucrose density gradient solution prepared in a measurement cell, which is then rotated to apply centrifugal force, thereby separating each particle contained in the measurement sample by particle size within the measurement cell (for example, Patent Document 1).

[0003] Conventionally, as a density gradient liquid preparation device for preparing such a density gradient liquid in a measurement cell, a device is known in which a solution injection needle is inserted into the measurement cell and the injection port at the tip of the needle is gradually moved from the bottom upward to inject sucrose solution so that its density gradually decreases. However, in this type of density gradient liquid preparation device, it is necessary to raise the position of the solution injection needle according to the water level of the injected sucrose solution, so that it is necessary to continuously measure the water level of the sucrose solution using a water level sensor. Therefore, if the measurement cell is relatively small compared to the water level sensor, such as a cuvette cell, it is not possible to measure the water level of the sucrose solution, and it is not possible to prepare a density gradient liquid.

[0004] In the past, a method for manually injecting a sucrose solution into a measurement cell using a syringe has been known as a method for preparing a density gradient solution without using a water level sensor. In this method, a low-density sucrose solution is first injected into the measurement cell, and then sucrose solutions with gradually increasing density are successively injected into the bottom of the measurement cell, thereby forming higher-density sucrose solution layers below the lower-density sucrose solution layers, thereby preparing a density gradient solution. However, this method requires the injection needle to be inserted and removed many times to inject the sucrose solution from the bottom of the measurement cell, which causes a problem of disturbance in the prepared density gradient solution. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] WO2018 / 092573 publication Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention has been made in consideration of the above-mentioned problems, and its main objective is to provide a density gradient liquid preparation device that can prepare a less turbulent density gradient liquid in a small measurement cell without using a water level sensor. [Means for solving the problem]

[0007] That is, the density gradient liquid preparation device of the present invention prepares a density gradient liquid consisting of a specified solution in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, and is characterized in that an injection port for injecting the solution is located at the bottom of the measurement cell placed at a specified position, and the solution is supplied from the injection port so that its density increases stepwise or continuously.

[0008] With such a device, by injecting a solution so that the density increases with the inlet positioned at the bottom of the measurement cell, it is possible to successively create higher density solution layers below lower density solution layers. Therefore, since there is no need to move the inlet when injecting the solution, a density gradient liquid can be created in a small measurement cell without using a water level sensor. In addition, because solutions with different densities are supplied from the inlet, which is located at the bottom of the measurement cell, there is no need to repeatedly insert and remove the injection needle forming the inlet into and from the measurement cell when preparing a density gradient solution, and this operation can be completed only once. Therefore, a clean density gradient solution with little disturbance can be prepared in a small measurement cell. In the present invention, the phrase "a state in which the injection port is located at the bottom of the measurement cell" means not only a state in which the injection port is in contact with the bottom of the measurement cell, but also a state in which the injection port is separated from the bottom of the measurement cell within a range in which a solution having a higher density can be introduced under the solution already supplied into the measurement cell.

[0009] A specific configuration of the density gradient liquid preparation device includes a solution preparation unit that prepares solutions having different densities and supplies them to the injection port, and the solution preparation unit supplies the solutions to the injection port so that their densities increase stepwise or continuously.

[0010] In this case, it is preferable that the solution preparation unit prepares the solutions having different densities by changing the mixing ratio of a plurality of solutions having known densities. In this way, for example, if at least two solutions with known densities are prepared, it is possible to prepare three or more solutions with different densities by changing the mixing ratio and mixing them, thereby eliminating the need to prepare a large number of solutions with adjusted densities in advance.

[0011] A specific configuration of the solution preparation unit includes a plurality of micropumps that respectively deliver the plurality of solutions of known density, a mixing unit that mixes the plurality of solutions of known density delivered from each of the micropumps, and a control unit that controls the amount of liquid delivered from each of the micropumps, and the control unit prepares the plurality of solutions with different densities by changing the ratio of the amount of liquid delivered from each of the micropumps. With this configuration, by controlling the amount of each solution of known density delivered by the micropump, the density can be controlled with high precision even if the measurement cell is small and the amount of density gradient solution produced is small.

[0012] When using a tubing pump as a micropump, for example, the tube may become worn out after long-term use, and the relationship between the rotation speed of the roller squeezing the tube and the amount of liquid delivered may become unstable. In such a case, the amount of density gradient liquid prepared in the measurement cell may differ from the target value, and if such a measurement cell is used in the line start method, the starting position of the sedimentation of the sample may change, resulting in a decrease in measurement accuracy. For this reason, it is preferable that the control unit further includes a calibration unit that acquires actual values ​​of the amount of liquid delivered by each of the plurality of micropumps of the known-density solution, and calibrates the plurality of micropumps based on the actual values ​​of the amount of liquid delivered.

[0013] It is preferable that the density gradient liquid preparation apparatus has a solution preparation unit that prepares the solution by mixing two known-density solutions having different densities, and the mixing unit includes a first flow path through which the first known-density solution flows, a second flow path through which the second known-density solution flows, and a junction flow path where the first flow path and the second flow path merge, and that the first flow path and the second flow path are formed symmetrically to each other across the junction flow path. In this way, turbulence can be generated in the junction flow path where the first flow path and the second flow path meet, thereby enabling the first solution with known density and the second solution with known density to be thoroughly mixed together.

[0014] In order to ensure that the first and second known-density solutions are mixed more thoroughly at the confluence, it is preferable that the total amount of liquid delivered by each of the micropumps is constant, and that the cross-sectional areas of the first flow path, the second flow path, and the confluence flow path in the mixing section are identical to each other. In this way, the pipeline resistance and viscous force act more easily, and the first and second known-density solutions are more likely to mix together. In other words, if the cross-sectional area of ​​the confluence flow path is too large compared to the first and second flow paths, there is a risk that the solutions of known density will not mix properly and will reach the injection port in a separated state, but by making the cross-sectional areas of the flow paths the same, the pipeline resistance between the tube and the solution and the viscous force between the solutions are increased, making it easier to generate vortexes in the confluence flow path.

[0015] It is also preferable that the density gradient liquid preparation apparatus further comprises a holding mechanism in which the injection port is formed at the tip of a straight tubular solution injection section and which holds the solution injection section so that it can slide straight along its tubular axis. With this configuration, after the solution has been injected into the measurement cell from the injection port, the solution injection part can be pulled straight out from the measurement cell, making it possible to prepare a density gradient solution with less turbulence.

[0016] The density gradient liquid preparation method of the present invention is a method for preparing a density gradient liquid consisting of a specified solution in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, characterized in that an injection port for injecting the solution is positioned at the bottom of the measurement cell placed at a specified position, and the solution is supplied from the injection port so that its density increases stepwise or continuously.

[0017] Such a density gradient preparation method can achieve the same effects as the density gradient liquid preparation apparatus of the present invention described above.

[0018] The particle size distribution measurement system of the present invention is characterized by comprising the density gradient fluid preparation apparatus of the present invention described above, and a centrifugal sedimentation type particle size distribution measurement apparatus that performs particle size distribution measurement by a line start method using the density gradient fluid prepared by the density gradient fluid preparation apparatus.

[0019] The particle size distribution measuring method of the present invention is characterized in that it measures particle size distribution by a line start method using a density gradient liquid prepared by the above-mentioned density gradient liquid preparation method of the present invention and a centrifugal sedimentation type particle size distribution measuring device.

[0020] Such a particle size distribution measuring system and particle size distribution measuring method can achieve the same effects as the density gradient liquid preparation apparatus of the present invention described above. Effect of the Invention

[0021] According to the present invention configured in this manner, it is possible to provide a density gradient fluid preparation device that can prepare a less turbulent density gradient fluid in a small measurement cell without using a water level sensor. [Brief description of the drawings]

[0022] [Figure 1] FIG. 1 is a perspective view showing a schematic configuration of a particle size distribution measuring system according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a front view of the density gradient solution preparation apparatus according to the embodiment. [Diagram 3] FIG. 2 shows a density gradient fluid prepared by the density gradient fluid preparation device of the same embodiment. [Figure 4] FIG. 2 is a plan view showing the configuration of a mixing unit of the density gradient fluid preparation apparatus according to the embodiment. [Diagram 5] FIG. 4 is a functional block diagram of a control unit of the solution preparation unit according to the embodiment. [Figure 6] 5A to 5C are diagrams for explaining the mixing ratios of sucrose solutions with known densities prepared by the solution preparation unit of the embodiment. [Figure 7] FIG. 4 is a diagram for explaining the operation of the density gradient solution preparation apparatus according to the embodiment. [Figure 8] FIG. 13 is a front view of a density gradient solution preparation device according to another embodiment. [Explanation of symbols]

[0023] 100 ···Density gradient liquid preparation device 3. Solution injection section 311...Inlet 4...Solution preparation section C Measuring cell DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] A density gradient liquid preparation apparatus 100 according to the present invention will be described below with reference to the drawings.

[0025] As shown in Fig. 1, the density gradient preparation apparatus 100 of this embodiment is used together with a centrifugal sedimentation type particle size distribution measuring apparatus 200 to constitute a particle size distribution measuring system 300. The density gradient preparation apparatus 100 is for preparing a density gradient solution composed of a sucrose solution in a measurement cell C (here, a rectangular parallelepiped cuvette cell having a square cross section) used in the particle size distribution measuring apparatus 200, and the particle size distribution measuring apparatus 200 measures the particle size distribution of a measurement sample by a line start method using the prepared density gradient solution. The density gradient preparation apparatus 100 will be described in detail below.

[0026] 1 and 2, the density gradient liquid preparation apparatus 100 includes a rectangular parallelepiped housing 1, a cell mounting section 2 on which a measurement cell C is placed, which is provided on one side surface 11 (hereinafter referred to as the front surface) of the housing 1, a solution injection section 3 having an injection port 311 for injecting a sucrose solution into the measurement cell C placed on the cell mounting section 2, and a solution preparation section 4 for preparing a sucrose solution of a desired density and supplying it to the injection port 311. With the injection port 311 positioned in the measurement cell C, the density gradient liquid preparation apparatus 100 injects a sucrose solution from the injection port 311 while changing its density, thereby preparing a density gradient liquid in the measurement cell C whose density increases from top to bottom in the vertical direction, as shown in FIG.

[0027] Thus, the density gradient solution preparation apparatus 100 is configured to supply sucrose solution from the injection port 311 of the solution injection section 3 so that its density increases stepwise, with the injection port 311 positioned at the bottom of the measurement cell C (i.e., with the injection port 311 fixed in position without movement). The specific configuration of each section will be described below.

[0028] The cell mounting portion 2 is provided at the lower part of the front surface 11 of the housing 1 so as to protrude from the front surface 11. The cell mounting portion 2 has a horizontal, planar cell mounting surface 21 on which the measurement cell C is placed.

[0029] The solution injection part 3 is provided directly above the cell mounting surface 21 in front view. Specifically, as shown in Figs. 2 and 3, the solution injection part 3 has a straight tube shape (straight thin tube shape) inside which the sucrose solution flows, and more specifically, is a liquid injection needle. An injection port 311 for injecting the sucrose solution into the measurement cell C is formed at the tip 31 of the solution injection part 3. The solution injection part 3 is held by a holding mechanism 5 provided on the front surface 11 of the housing 1 with the tip 31 facing straight down (i.e., the tube axis direction and the up-down direction coincide).

[0030] The holding mechanism 5 is configured to hold the solution injection part 3 so that it can slide straight along the vertical direction with the tip part 31 facing downward. Specifically, the holding mechanism 5 includes a holding block 51 to which the base end part 32 of the solution injection part 3 is connected, and a linear guide 52 that guides the holding block 51 along the tube axis direction of the solution injection part 3 (here, the vertical direction).

[0031] The holding block 51 is a block having a circular shape when viewed from the front. As shown in Fig. 4, an internal flow path 511 through which the sucrose solution flows is formed inside the holding block 51. The downstream end of this internal flow path 511 opens to the bottom surface of the holding block 51, thereby forming an outlet 51о through which the sucrose solution is led to the solution injecting unit 3. The base end 32 of the solution injecting unit 3 is attached so as to communicate with this outlet 51о.

[0032] The linear guide 52 includes, for example, a guide rail (not shown) that extends straight in the vertical direction within the housing 1, and a slide member 521 that slides along the guide rail. The holding block 51 is attached to the slide member 521.

[0033] The holding mechanism 5 is also provided with an operation unit 53 for vertically moving the solution injection unit 3. Specifically, the operation unit 53 is configured with a convex portion provided on the surface of the front side of the holding block 51.

[0034] The solution preparation unit 4 prepares a sucrose solution of a desired density by mixing a plurality of (here, two) sucrose solutions 41 with known densities (hereinafter, referred to as sucrose solutions with known densities), and supplies this to the solution injection unit 3. Specifically, the solution preparation unit 4 prepares sucrose solutions with gradually increasing densities and supplies this to the solution injection unit 3.

[0035] More specifically, as shown in FIG. 2, the solution preparation unit 4 includes a first sucrose solution of known density 41a having a predetermined first density, a second sucrose solution of known density 41b having a second density higher than the first density, a first micropump 42a and a second micropump 42b for pumping the sucrose solutions of known density 41a, 41b, respectively, a mixer 43 for mixing the sucrose solutions of known density 41a, 41b pumped from the micropumps 42a, 42b and supplying the mixed solution to the solution injection unit 3, and a control unit 44.

[0036] As shown in FIG. 2, each of the sucrose solutions 41a and 41b with known densities is contained in a container, and is placed on the cell placement surface 21 of the housing 1 with the measurement cell C interposed therebetween.

[0037] Each of the micropumps 42a, 42b is installed above the container on the front surface 11 of the housing 1, and sucks out the sucrose solutions 41a, 41b of known density from the respective containers through tubes and sends the liquid to the mixing unit 43. This micropump is, for example, a so-called roller pump (tubing pump) that includes a soft tube (such as a silicon tube) through which the liquid flows and a rotating roller that squeezes the tube, and sends out the liquid by squeezing the tube with the rotating roller.

[0038] The mixing section 43 includes a first flow path 431 through which the first sucrose solution with known density 41a delivered from the first micropump 42a flows, a second flow path 432 through which the second sucrose solution with known density 41b delivered from the second micropump 42b flows, and a junction flow path 433 where the first flow path 431 and the second flow path 432 join. The sucrose solutions with known density 41a and 41b delivered from the respective micropumps join at the junction flow path 433 and are mixed.

[0039] As shown in Fig. 4, the first flow path 431, the second flow path 432, and the junction flow path 433 are configured by the internal flow path 511 formed inside the holding block 51. In a front view, the junction flow path 433 is formed straight along the vertical direction, and the first flow path 431 and the second flow path 432 are formed to be symmetrical with respect to each other with the junction flow path 433 in between. Here, the first flow path 431, the second flow path 432, and the junction flow path 433 are connected to each other to form a T-shape or a Y-shape. The first flow path 431, the second flow path 432, and the junction flow path 433 are formed so that their respective flow path cross-sectional areas are the same.

[0040] The control unit 44 is a general-purpose or dedicated computer equipped with a CPU, a memory, an input / output interface, etc., and is provided inside the housing 1. The control unit 44 at least performs the functions of an input receiving unit 441, a storage unit 442, a pump control unit 443, and a calibration unit 444, as shown in Fig. 5, by causing the CPU and peripheral devices to cooperate with each other in accordance with a predetermined program stored in a predetermined area of ​​the memory.

[0041] The input receiving unit 441 receives various input signals from the user. For example, the input receiving unit 441 receives an input signal indicating the start of preparation of a sucrose solution from the user. The input receiving unit 441 also receives from the user actual values ​​of the amount of liquid delivered by each of the pumps 42a and 42b.

[0042] The storage unit 442 is set in a predetermined area of ​​the memory, and stores in advance the mixing ratio data indicating the mixing ratio of each of the known-density sucrose solutions 41a, 41b, or an equivalent ratio (for example, the liquid delivery amount and / or the ratio of each of the micro pumps 42a, 42b, the number of rotations of the rollers of each of the micro pumps 42a, 42b and / or the ratio of each of the micro pumps 42a, 42b, etc.). As shown in FIG. 6, for example, this mixing ratio data indicates the relationship between the elapsed time from the start of preparation of the sucrose solution and the mixing ratio of each of the known-density sucrose solutions 41a, 41b, and here, the ratio of the second known-density sucrose solution 41b, which has a higher density, is set to increase stepwise (here, 11 steps) over time. The storage unit 442 also stores pump performance data indicating the relationship between the number of rotations of the rollers of each of the micro pumps 42a, 42b and the liquid delivery amount.

[0043] The pump control unit 443 operates each of the micro pumps 42a, 42b by referring to the mixing ratio data and pump performance data stored in the memory unit 442. Specifically, the pump control unit 443 controls the roller rotation speed and the ratio of each of the micro pumps 42a, 42b so that the roller rotation speed and the ratio correspond to the mixing ratio indicated by the mixing ratio data. Here, the pump control unit 443 controls each of the micro pumps 42a, 42b so that the total amount of liquid delivered by each of the micro pumps 42a, 42b is constant regardless of the mixing ratio.

[0044] The calibration unit 444 calibrates the liquid delivery amount of each micropump 42a, 42b. Specifically, when the calibration unit 444 acquires the actual value of the liquid delivery amount of each micropump 42a, 42b from the input reception unit 441, the calibration unit 444 compares the actual value with the liquid delivery amount of each micropump 42a, 42b indicated by the pump performance data. Then, the pump performance data is updated so that the liquid delivery amount indicated by the pump performance data matches the actual value of the liquid delivery amount. Note that the actual value of the liquid delivery amount of each micropump may be measured by any method, for example, by the user weighing the reduction amount of each sucrose solution 41a, 41b of known density contained in the solution.

[0045] Next, the operation of preparing a density gradient fluid by the density gradient fluid preparation apparatus 100 will be described with reference to FIG.

[0046] First, the user sets the first known-density sucrose solution 41a, the second known-density sucrose solution 41b, and the measurement cell C on the cell placement surface 21, and presses down the operation part 53 of the holding mechanism 5 with a finger to place the inlet 311 in the measurement cell C (FIG. 7(a)). With the inlet 311 positioned at the bottom of the measurement cell C, a predetermined start button provided on the density gradient solution preparation device 100 is turned on to start preparation of the sucrose solution by the solution preparation part 4. The solution preparation part 4 first prepares a sucrose solution with a low density (only the first known-density sucrose solution 41a) and supplies it to the solution injection part 3 (FIG. 7(b)). Then, the solution preparation part 4 reduces the proportion of the amount of the first known-density sucrose solution 41a sent and simultaneously increases the proportion of the amount of the second known-density sucrose solution 41b sent, and supplies the sucrose solution to the solution injection part 3 with a gradually increasing density (FIG. 7(c)). Then, when a predetermined amount of density gradient liquid has been prepared in the measurement cell C, the user pushes up the operating part 53 of the holding mechanism 5 with his / her finger and pulls the solution injection part 3 straight out from the measurement cell C (Figure 7(d)).

[0047] According to the density gradient liquid preparation device 100 of the present embodiment configured as described above, by injecting a solution so that the density becomes high with the inlet 311 positioned at the bottom of the measurement cell C, a higher density solution layer can be successively created under a lower density solution layer. Therefore, since there is no need to move the inlet 311 when injecting a solution, a density gradient liquid can be prepared in the small measurement cell C without using a water level sensor. In addition, since solutions with different densities are supplied from the inlet 311 with the inlet 311 positioned at the bottom of the measurement cell C, there is no need to insert and remove the injection needle forming the inlet 311 into and from the measurement cell C many times when preparing a density gradient liquid, and the operation can be completed only once. Therefore, a clean density gradient liquid with little disturbance can be prepared in the small measurement cell C.

[0048] The present invention is not limited to the above-described embodiment.

[0049] For example, in the above embodiment, the sucrose solution is supplied from the inlet 311 so that its density increases stepwise, but this is not limited thereto. In other embodiments, the sucrose solution may be supplied from the inlet 311 so that its density increases continuously.

[0050] In the above embodiment, the density gradient solution is a sucrose solution, but this is not limiting, and in other embodiments, the density gradient solution may be other solutions, such as halocarbons.

[0051] In addition, the density gradient solution preparation apparatus 100 of other embodiments may not include the solution preparation unit 4. In this case, the density gradient solution preparation apparatus 100 may include a plurality of sucrose solutions with different densities that have been prepared in advance, and these sucrose solutions may be supplied to the inlet 311 in the order of decreasing density.

[0052] In the above embodiment, the solution injection part 3 is raised and lowered by operating the operation part 53 of the holding mechanism 5 with a finger, but this is not limited thereto. In other embodiments, the solution injection part 3 may be configured to be raised and lowered automatically.

[0053] In the above embodiment, the solution injection part 3 is slidably moved relative to the measurement cell C, but this is not limited thereto. In other embodiments, the cell mounting part 2 may be configured so that the solution injection part 3 is fixed and the measurement cell C is slidably moved relative to the solution injection part 3.

[0054] The density gradient liquid preparation apparatus 100 in the above embodiment is used together with the particle size distribution measuring apparatus 200, but is not limited to this and may be used alone. Furthermore, the measurement cell C is not limited to a cuvette cell and may be of another type.

[0055] 8, the density gradient solution preparation apparatus 100 may include a washing mechanism 6 for washing the flow path through which the sucrose solution flows. As shown in FIG. 8, the washing mechanism 6 includes washing solutions 61a, 61b (specifically, pure water) placed on the cell mounting surface 21, micropumps 42a, 42b for sucking up the washing solution 61 and supplying it to the injection port 311, switching valves (specifically, three-way valves) 62a, 62b for switching the suction ports of the micropumps 42a, 42b between the washing solutions 61a, 61b and the sucrose solutions of known density 41a, 41b, and a control unit 44 for controlling the operations of the micropumps 42a, 42b and the switching valves 62a, 62b.

[0056] The cleaning mechanism 6 cleans the flow path through which the sucrose solution flows before the density gradient solution preparation operation of the density gradient solution preparation device 100 starts or after the density gradient solution preparation operation ends. Specifically, the control unit 44 controls the switching valves 62a, 62b to switch the suction ports of the micropumps 42a, 42b from the sucrose solutions of known density 41a, 41b to the cleaning solutions 61a, 61b. The control unit 44 then rotates the rollers of the micropumps 42a, 42b to suck up the cleaning solution, supplies it to the solution injection unit 3, and ejects it from the injection port 311. In this way, the cleaning mechanism 6 cleans the flow path through which the sucrose solution flows.

[0057] Furthermore, the present invention is not limited to the above-described embodiment, and it goes without saying that various modifications are possible without departing from the spirit and scope of the present invention. [Industrial Applicability]

[0058] According to the density gradient fluid preparation device of the present invention, a density gradient fluid with little turbulence can be prepared in a small measurement cell without using a water level sensor.

Claims

1. A density gradient liquid made of a predetermined solution is prepared in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, an inlet for injecting the solution; a solution preparation unit that prepares the solutions having different densities and supplies the solutions to the inlet; A density gradient solution preparation device in which, with the injection port positioned at the bottom of the measurement cell placed at a predetermined position, the solution preparation unit supplies the solution to the injection port so that its density increases stepwise.

2. 2. The density gradient solution producing apparatus according to claim 1, wherein the solution preparation section prepares the solutions having different densities by changing a mixing ratio of a plurality of solutions having known densities.

3. The solution preparation unit is A plurality of micropumps for pumping the plurality of solutions having known densities, respectively; a mixing unit that mixes the plurality of solutions of known density pumped from each of the micropumps; a control unit for controlling the amount of liquid delivered by each of the micropumps; 3. The density gradient solution producing apparatus according to claim 2, wherein the control unit prepares a plurality of solutions having different densities by changing a ratio of the liquid delivery rates of the micropumps.

4. 4. The density gradient liquid preparation apparatus according to claim 3, further comprising a calibration unit, wherein the control unit acquires actual values ​​of the amount of liquid delivered by each of the plurality of micropumps of a solution of known density, and calibrates the plurality of micropumps based on the actual values ​​of the amount of liquid delivered.

5. the solution preparation unit prepares the solution by mixing two solutions of known density having different densities, The mixing section is a first flow path through which the first solution having a known density flows; a second flow path through which the second solution having a known density flows; a junction flow path where the first flow path and the second flow path join together, 4. The density gradient liquid preparation apparatus according to claim 3, wherein the first flow path and the second flow path are formed symmetrically to each other with the junction flow path in between.

6. The total amount of liquid delivered by each of the micropumps is constant; 6. The density gradient liquid preparation apparatus according to claim 5, wherein the first flow path, the second flow path and the merging flow path have the same flow path cross-sectional area.

7. The injection port is formed at the tip of a solution injection part having a straight tube shape, 2. The density gradient solution preparation apparatus according to claim 1, further comprising a holding mechanism that holds the solution injection section so that the solution injection section can slide along its axial direction.

8. A method for preparing a density gradient solution of a predetermined solution in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, comprising: A method for preparing a density gradient solution, comprising: positioning an inlet for injecting the solution at the bottom of the measurement cell placed at a predetermined position; and supplying the solution from the inlet so that its density increases stepwise.

9. The density gradient liquid preparation apparatus according to claim 1 , and a centrifugal sedimentation type particle size distribution measuring device that performs particle size distribution measurement by a line start method using the density gradient liquid prepared by the density gradient liquid preparation device.

10. A method for measuring particle size distribution, comprising the steps of: measuring particle size distribution by a line start method using a density gradient liquid prepared by the density gradient liquid preparation method according to claim 8 and a centrifugal sedimentation type particle size distribution measuring device.

11. A method for preparing a density gradient solution made of a predetermined solution in a measurement cell for a centrifugal sedimentation type particle size distribution measurement device, comprising: an injection port for injecting the solution, the injection port being formed at a tip end of a straight tubular solution injection section; a holding mechanism for holding the solution injection part so as to be slidable along the tube axis direction with a tip portion of the solution injection part facing downward, the holding mechanism including a linear guide for guiding the solution injection part along the tube axis direction; a solution preparation unit that prepares the solutions having different densities and supplies the solutions to the inlet; A density gradient liquid preparation device in which, with the injection port positioned at the bottom of the measurement cell placed at a predetermined position, the solution preparation unit supplies the solution to the injection port so that the density of the solution increases stepwise or continuously.

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