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

Abstract

Provided is a density gradient liquid production apparatus that produces a density gradient liquid within a measurement cell for a centrifugal-precipitation-type particle diameter distribution measurement device, the density gradient liquid production apparatus comprising: a first solution preparation unit that mixes a plurality of first reference solutions having mutually different concentrations of a flocculation-inhibiting component for inhibiting flocculation of particles, to prepare a first solution having a prescribed target concentration and a first density; a second solution preparation unit that mixes a plurality of second reference solutions having mutually different concentrations of the flocculation-inhibiting component to prepare a second solution having the target concentration and a second density different from the first density; and a mixed solution preparation unit that mixes the first solution and the second solution to thereby generate a mixed solution having the target concentration, and that varies the density of the mixed solution and supplies the mixed solution into the measurement cell.

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 the same.

Background Art

[0002] In the line start method using a centrifugal sedimentation type particle size distribution measurement device, a measurement sample is injected into a sucrose density gradient liquid prepared in a measurement cell, and this is rotated to apply a centrifugal force, so that each particle contained in the measurement sample is separated by particle size in the measurement cell.

[0003] Conventionally, the preparation of the density gradient liquid in the measurement cell has been performed using a density gradient liquid preparation device. As such a density gradient liquid preparation device, for example, sucrose solutions having different densities are prepared by mixing two sucrose solutions having different densities at different ratios, and this is supplied to the measurement cell so that the density gradually increases to prepare a density gradient liquid (for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Incidentally, the density gradient solution used in the line-start method needs to be prepared by adjusting its pH as far away from the isoelectric point as possible for each sample type and particle size, so that the particles contained in the injected sample do not aggregate in the solution. Conventionally, to prepare a density gradient solution with a target pH (hereinafter also referred to as target pH), multiple sucrose solutions with the target pH are prepared manually using pH adjusting agents such as acidic or alkaline solutions, and these are then set in a density gradient solution preparation device to produce a density gradient solution with the target pH. However, with this method, for example, when measuring many samples of different types or particle sizes, or when conducting experiments with varying pH values ​​of the density gradient solution, the user has to prepare a huge number of sucrose solutions with different densities and pH levels manually for each of the multiple density gradient solutions with different pH values ​​to be prepared, which is extremely inefficient. The same problem can be said when suppressing particle aggregation by adjusting the concentration of surfactant in the density gradient solution.

[0006] This invention has been made in view of the above problems, and its main objective is to provide a density gradient liquid preparation device that can efficiently prepare multiple density gradient liquids with different concentrations of aggregation-inhibiting components. [Means for solving the problem]

[0007] In other words, the density gradient liquid preparation apparatus according to the present invention prepares a density gradient liquid in a measuring cell for a centrifugal sedimentation type particle size distribution measuring apparatus, and is characterized by comprising: a first solution preparation unit that mixes a plurality of first reference solutions having different concentrations of aggregation-inhibiting components to prepare a first solution having a predetermined target concentration and a first density; a second solution preparation unit that mixes a plurality of second reference solutions having different concentrations of the aggregation-inhibiting components to prepare a second solution having the target concentration and a second density different from the first density; and a mixed solution preparation unit that mixes the first solution and the second solution to generate a mixed solution of the target concentration and changes its density before supplying it into the measuring cell.

[0008] With this method, by mixing multiple reference solutions with different concentrations of agglutination-inhibiting components, a first solution and a second solution with the target concentration can be prepared, and a density gradient solution with the target concentration can be created in the measurement cell using these solutions. This allows for the efficient creation of multiple density gradient solutions with different concentrations of agglutination-inhibiting components. In other words, using the density gradient solution preparation device of the present invention, the user does not need to individually prepare the first solution and the second solution by adjusting the concentration of the agglutination-inhibiting component according to the desired density gradient solution concentration. Instead, by preparing at least two first reference solutions and two second reference solutions with different concentrations of agglutination-inhibiting components for preparing the first and second solutions respectively, a density gradient solution with any desired concentration of agglutination-inhibiting component can be created using these solutions. This allows for the efficient creation of multiple density gradient solutions with different concentrations of agglutination-inhibiting components. Specifically, this aggregation-inhibiting component is hydrogen ions (H), which are components that determine the pH of a solution. + ) and surfactants, etc.

[0009] Preferably, the first solution preparation unit prepares the first solution by mixing a plurality of first reference solutions having equal densities, and the second solution preparation unit prepares the second solution by mixing a plurality of second reference solutions having equal densities. In this way, it is not necessary to adjust the mixing ratio of each reference solution so that the first and second solutions reach their respective target densities, making it easier to prepare the first and second solutions.

[0010] The density gradient liquid preparation apparatus is configured such that the aggregation-inhibiting component is hydrogen ions (H + Preferably, the first solution preparation unit prepares the first solution by mixing the acidic first standard solution and the alkaline first standard solution, and the second solution preparation unit prepares the second solution by mixing the acidic second standard solution and the alkaline second standard solution. In this way, density gradient solutions with acidic, neutral, and alkaline pH values ​​can be prepared.

[0011] A specific configuration of the density gradient liquid preparation apparatus includes a first solution preparation unit and a second solution preparation unit, each comprising a plurality of primary pumps for supplying a plurality of the standard solutions, and a primary mixing unit for mixing the standard solutions supplied from each primary pump. By changing the ratio of the supply volumes from each primary pump, a solution with a desired concentration of aggregation-inhibiting components can be prepared.

[0012] A specific configuration of the density gradient liquid preparation apparatus includes a target concentration acquisition unit that obtains the target concentration value from the user, and a primary pump control unit that controls the rotation speed of the primary pumps provided in the first solution preparation unit and the second solution preparation unit, respectively, according to the acquired target concentration value.

[0013] A specific configuration of the density gradient liquid preparation apparatus includes a mixed solution preparation unit comprising two secondary pumps that deliver the first solution and the second solution respectively, and a secondary mixing unit that mixes the first solution and the second solution delivered from each secondary pump, thereby changing the density of the resulting mixed solution by changing the ratio of the liquid delivery amounts from each secondary pump.

[0014] In order to prepare the required amount of density gradient liquid according to the capacity of the measurement cell, it is preferable to further include a cell capacity acquisition unit that obtains the capacity of the measurement cell from the user, and a secondary pump control unit that controls the rotation speed of each secondary pump according to the acquired capacity of the measurement cell.

[0015] Furthermore, it is preferable that both the primary pump and the secondary pump in the density gradient liquid preparation apparatus are micropumps. With this configuration, the flow rates of each reference solution, the first solution, and the second solution can be controlled by a micropump, allowing for precise control of the density and aggregation-inhibiting component concentration even when the measurement cell has a small capacity and the amount of density gradient solution prepared is small.

[0016] The method for producing a density gradient liquid of the present invention is a method for producing a density gradient liquid in a measurement cell for a centrifugal sedimentation type particle size distribution measuring device, comprising: a first solution preparation step of mixing a plurality of first reference solutions having different concentrations of an aggregation suppressing component to prepare a first solution having a predetermined target concentration and a first density; a second solution preparation step of mixing a plurality of second reference solutions having different concentrations of the aggregation suppressing component to prepare a second solution having the target concentration and a second density different from the first density; and a mixed solution preparation step of mixing the first solution and the second solution to generate a mixed solution having the target concentration and supplying the mixed solution into the measurement cell while changing its density.

[0017] With such a method for producing a density gradient, the same operational effects as those of the density gradient liquid production device of the present invention described above can be achieved.

[0018] The particle size distribution measurement system of the present invention is characterized by comprising the density gradient liquid production device of the present invention described above and a centrifugal sedimentation type particle size distribution measuring device that measures the particle size distribution by the line start method using the density gradient liquid produced by the density gradient liquid production device.

[0019] The particle size distribution measurement method of the present invention is characterized by measuring the particle size distribution by the line start method using the density gradient liquid produced by the method for producing a density gradient liquid of the present invention described above and a centrifugal sedimentation type particle size distribution measuring device.

[0020] With such a particle size distribution measurement system and particle size distribution measurement method, the same operational effects as those of the density gradient liquid production device of the present invention described above can be achieved.

Effects of the Invention

[0021] According to the present invention configured as described above, a density gradient liquid production device capable of efficiently producing a plurality of density gradient liquids having different concentrations of an aggregation suppressing component can be provided.

Brief Description of the Drawings

[0022] [Figure 1] A diagram schematically showing the configuration of the density gradient liquid preparation apparatus of this embodiment. [Figure 2] A functional block diagram of the density gradient liquid preparation apparatus of this embodiment. [Figure 3] A diagram for explaining the operation of the density gradient liquid preparation apparatus of this embodiment. [Figure 4] A diagram schematically showing the configuration of the density gradient liquid preparation apparatus of another embodiment. [Figure 5] A functional block diagram of the density gradient liquid preparation apparatus of another embodiment.

Explanation of Reference Numerals

[0023] 100 ··· Density gradient liquid preparation apparatus 1 ··· First solution preparation unit 11a, b ··· First reference sucrose solution (first reference solution) 2 ··· Second solution preparation unit 21a, b ··· Second reference sucrose solution (second reference solution) 3 ··· Mixed solution preparation unit 31 ··· First sucrose solution 32 ··· Second sucrose solution C ··· Measurement cell

Mode for Carrying Out the Invention

[0024] The 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 liquid preparation apparatus 100 of this embodiment is used together with a centrifugal sedimentation type particle size distribution measurement apparatus 200 to constitute a particle size distribution measurement system 300. The density gradient liquid preparation apparatus 100 prepares a density gradient liquid composed of a sucrose solution in a measurement cell C (for example, a cuboid cell having a rectangular cross section, etc.) used in the particle size distribution measurement apparatus 200, and the particle size distribution measurement apparatus 200 measures the particle size distribution of a measurement sample by the line start method using the prepared density gradient liquid.

[0026] However, this density gradient liquid preparation device 100 prepares hydrogen ions (H) according to the sample being measured. + The system is configured to receive a target concentration (hereinafter also referred to as the target hydrogen ion concentration) from the user and to produce a density gradient solution with the target hydrogen ion concentration by mixing multiple sucrose solutions with different hydrogen ion concentrations and densities.

[0027] Specifically, as shown in Figure 1, the density gradient liquid preparation apparatus 100 includes a first solution preparation unit 1 that mixes multiple sucrose solutions to prepare a first sucrose solution 31 with a target hydrogen ion concentration and a first density; a second solution preparation unit 2 that mixes multiple sucrose solutions to prepare a second sucrose solution 32 with a target hydrogen ion concentration and a second density higher than the first density; a mixed solution preparation unit 3 that mixes the prepared first sucrose solution 31 and second sucrose solution 32 to generate a mixed sucrose solution with a target hydrogen ion concentration and changes its density before supplying it into the measurement cell C; and a control unit 4 that controls each solution preparation unit.

[0028] (1st solution preparation section 1) The first solution preparation unit 1 prepares a first sucrose solution 31 by mixing several (in this case, two) sucrose solutions 11a and 11b (hereinafter also referred to as the first standard sucrose solution) whose hydrogen ion concentration and density are known, and supplies this to the mixed solution preparation unit 3.

[0029] Specifically, the first solution preparation unit 1 comprises two types of first standard sucrose solutions 11a and 11b having different hydrogen ion concentrations and both having a first density, two primary pumps 12a and 12b that deliver each of the first standard sucrose solutions 11a and 11b, and a primary mixing unit 13 that mixes the first standard sucrose solutions 11a and 11b delivered from the primary pumps 12a and 12b and supplies the mixture to the mixed solution preparation unit 3. In this embodiment, one of the two types of first standard sucrose solutions 11a and 11b is an acidic solution with a pH of less than 7, and the other is an alkaline solution with a pH greater than 7. The first solution preparation unit 1 is configured to prepare a first sucrose solution 31 with a desired pH by changing the ratio of the liquid delivery amounts from the primary pumps 12a and 12b based on a control signal received from the control unit 4.

[0030] Each primary pump 12a and 12b draws out the respective first standard sucrose solutions 11a and 11b contained in the containers via a tube and sends them to the primary mixing unit 13. These primary pumps 12a and 12b are capable of continuously supplying minute amounts of solution and are micropumps such as roller pumps (tubing pumps) that supply the solution by squeezing a flexible tube (such as a silicone tube) through which the solution flows with a rotating roller.

[0031] The primary mixing section 13 comprises multiple primary branch channels 131a and 131b through which the first standard sucrose solutions 11a and 11b supplied from the respective primary pumps 12a and 12b flow, and a primary confluence channel 132 through which the primary branch channels 131a and 131b merge. The first standard sucrose solutions 11a and 11b supplied from the respective primary pumps 12a and 12b are mixed by merging in the primary confluence channel 132 to form a first sucrose solution 31 having a target hydrogen ion concentration and a first density.

[0032] (Second solution preparation section 2) The second solution preparation unit 2 prepares a second sucrose solution 32 by mixing several (in this case, two) sucrose solutions 21a and 21b (hereinafter also referred to as the second standard sucrose solution) whose hydrogen ion concentration and density are known, and supplies this to the mixed solution preparation unit 3.

[0033] Specifically, the second solution preparation unit 2 comprises two types of second standard sucrose solutions 21a and 21b having different hydrogen ion concentrations and both having second density, two primary pumps 22a and 22b that each pump one of the second standard sucrose solutions 21a and 21b, and a primary mixing unit that mixes the second standard sucrose solutions 21a and 21b pumped from each primary pump 22a and 22b and supplies the mixture to the mixed solution preparation unit 3. In this embodiment, one of the two types of second standard sucrose solutions 21a and 21b is an acidic solution with a pH of less than 7, and the other is an alkaline solution with a pH greater than 7. The second solution preparation unit 2 is configured to prepare a second sucrose solution 32 with a desired hydrogen ion concentration by changing the ratio of the liquid volume pumped by each primary pump 22a and 22b based on a control signal received from the control unit 4. The configuration of the primary pumps 22a, 22b and primary mixing unit 23 in the second solution preparation unit 2 is the same as the configuration of the primary pumps 12a, 12b and primary mixing unit 13 in the first solution preparation unit 1 described above, and a detailed explanation is omitted here.

[0034] (Mixed solution preparation section 3) The mixed solution preparation unit 3 includes a first sucrose solution 31 (target hydrogen ion concentration and first density) supplied from the first solution preparation unit 1, a second sucrose solution 32 (target hydrogen ion concentration and second density) supplied from the second solution preparation unit 2, a plurality (in this case, two) of secondary pumps 33a and 33b that supply the first sucrose solution 31 and the second sucrose solution 32 respectively, and a secondary mixing unit 34 that mixes the first sucrose solution 31 and the second sucrose solution 32 supplied from each of the secondary pumps 33a and 33b and supplies the mixed sucrose solution to the measurement cell C. The mixed solution preparation unit 3 is configured to change the density of the generated mixed sucrose solution by changing the ratio of the liquid supply amounts from each of the secondary pumps 33a and 33b based on control signals received from the control unit 4. In this embodiment, the first sucrose solution 31 supplied from the first solution preparation unit 1 and the second sucrose solution 32 supplied from the second solution preparation unit 2 are each contained within containers.

[0035] Each of the secondary pumps 33a and 33b draws out the first sucrose solution 31 and the second sucrose solution 32 contained in the containers via tubes and delivers them to the secondary mixing unit 34. These secondary pumps 33a and 33b are capable of continuously delivering minute amounts of solution and, like the primary pumps, are micropumps such as roller pumps.

[0036] The secondary mixing section 34 comprises a plurality of secondary branch channels 341a and 341b through which the first sucrose solution 31 and the second sucrose solution 32, respectively, supplied from the secondary pumps 33a and 33b, flow, and a secondary confluence channel 342 through which the secondary branch channels 341a and 341b merge. The first sucrose solution 31 and the second sucrose solution 32 supplied from the secondary pumps 33a and 33b are mixed by merging in the secondary confluence channel 342. A solution inlet is provided at the downstream end of this secondary confluence channel 342 for injecting the mixed solution into a measuring cell C placed at a predetermined position.

[0037] (Control Unit 4) The control unit 4 is a general-purpose or dedicated computer equipped with a CPU, memory, and input / output interfaces. This control unit 4, by coordinating the CPU and peripheral devices according to a predetermined program stored in a predetermined area of ​​memory, performs at least the functions of a target hydrogen ion concentration acquisition unit 41, a first storage unit 42, a primary pump control unit 43, a cell capacity acquisition unit 44, a second storage unit 45, and a secondary pump control unit 46, as shown in Figure 2.

[0038] The target hydrogen ion concentration acquisition unit 41 acquires the target hydrogen ion concentration value entered by the user. The user enters this target hydrogen ion concentration value using an input means such as a keyboard or touch panel. Once the target hydrogen ion concentration acquisition unit 41 acquires the target hydrogen ion concentration value, it transmits it to the primary pump control unit 43.

[0039] The first storage unit 42 is set in a predetermined area of ​​the memory and pre-stores first mixing ratio data that shows the relationship between the mixing ratio of each first reference sucrose solution 11a, 11b, or an equivalent ratio (for example, the amount of liquid delivered by each primary pump 12a, 12b and / or its ratio, the rotation speed of the rollers of each primary pump 12a, 12b and / or its ratio, etc.) and the hydrogen ion concentration value of the first sucrose solution 31 after mixing. Similarly, the first storage unit 42 pre-stores second mixing ratio data that shows the relationship between the mixing ratio of each second reference sucrose solution 21a, 21b, or an equivalent ratio (for example, the amount of liquid delivered by each primary pump 22a, 22b and / or its ratio, the rotation speed of the rollers of each primary pump 22a, 22b and / or its ratio, etc.) and the hydrogen ion concentration value of the second sucrose solution 32 after mixing. The first storage unit 42 also stores primary pump performance data showing the relationship between the amount of rotation of the rollers of each primary pump 12, 22 and the amount of fluid delivered.

[0040] When the primary pump control unit 43 obtains the target hydrogen ion concentration value from the target hydrogen ion concentration value acquisition unit, it refers to the first mixing ratio data, the second mixing ratio data, and the primary pump performance data stored in the first storage unit 42, and operates the primary pumps 12 and 22 provided in the first solution preparation unit 1 and the second solution preparation unit 2, respectively. Specifically, it controls the roller rotation speed and ratio of each primary pump 12 and 22 to correspond to the mixing ratio indicated by each mixing ratio data. Here, the primary pump control unit 43 controls each primary pump 12 and 22 to adjust predetermined amounts of the first sucrose solution 31 and the second sucrose solution 32, respectively, as set in advance by the user.

[0041] The cell capacity acquisition unit 44 acquires the capacity value of the measurement cell C entered by the user. The user inputs this capacity value using an input means such as a keyboard or touch panel. Once the cell capacity acquisition unit 44 acquires the cell capacity value, it transmits it to the secondary pump control unit 46.

[0042] The second storage unit 45 is set in a predetermined area of ​​the memory and pre-stores density gradient data that shows the time change of the mixing ratio of the first sucrose solution 31 and the second sucrose solution 32, or an equivalent ratio (for example, the amount of liquid delivered by each secondary pump 33a, 33b and / or their ratio, the rotation speed of the rollers of each secondary pump 33a, 33b and / or their ratio, etc.). This density gradient data shows, for example, the relationship between the elapsed time since the start of preparation of the mixed solution and the mixing ratio of the first sucrose solution 31 and the second sucrose solution 32, and is set, for example, so that the density of the mixed solution increases (or decreases) over time. The second storage unit 45 also stores secondary pump performance data that shows the relationship between the amount of rotation of the rollers of each secondary pump 33a, 33b and the amount of liquid delivered.

[0043] When the secondary pump control unit 46 obtains the cell capacity value from the cell capacity acquisition unit 44, it refers to the density gradient data and secondary pump performance data stored in the second storage unit 45 and operates each of the secondary pumps 33a and 33b. Specifically, it controls the roller rotation speed and ratio of each secondary pump 33a and 33b to correspond to the mixing ratio indicated by each density gradient data. Here, the secondary pump control unit 46 controls each of the secondary pumps 33a and 33b so that the total amount of the mixed solution to be adjusted does not exceed the cell capacity value.

[0044] Next, the operation of creating a density gradient liquid using this density gradient liquid preparation device 100 will be explained with reference to Figure 3.

[0045] First, the user prepares two types of first standard sucrose solutions 11a and 11b and two types of second standard sucrose solutions 21a and 21b, whose hydrogen ion concentration and density have been pre-adjusted to predetermined values, and sets them in the designated positions on the density gradient liquid preparation device 100 (Figure 3(a)). Next, the user operates, for example, the control panel on the density gradient liquid preparation device 100 to input the target hydrogen ion concentration value and the cell volume value, and then turns on the density gradient liquid preparation start button to start the preparation of the density gradient liquid. Then, the first solution preparation unit 1 first mixes the two first standard sucrose solutions 11a and 11b to prepare a first sucrose solution 31 that has the target hydrogen ion concentration and the first density, and supplies this to the container of the mixing and adjustment unit. Simultaneously, the second solution preparation unit 2 mixes the two second standard sucrose solutions 21a and 21b to prepare a second sucrose solution 32 that has the target hydrogen ion concentration and second density, and supplies this to the container of the mixing and adjusting unit (Figure 3(b)). Once the first solution preparation unit 1 and the second solution preparation unit 2 have prepared a predetermined amount or more of the first sucrose solution 31 and the second sucrose solution 32, the mixed solution preparation unit 3 then prepares a mixed solution with the target hydrogen ion concentration and supplies this to the measurement cell C (Figure 3(c)). Specifically, the mixed solution is supplied to the measurement cell C while changing its density by mixing the first sucrose solution 31 and the second sucrose solution 32 at different mixing ratios. The mixed solution preparation unit 3 terminates the preparation of the mixed solution when the total volume of the prepared mixed solution reaches the cell capacity value.

[0046] With the density gradient liquid preparation apparatus 100 of this embodiment configured in this way, a first sucrose solution 31 and a second sucrose solution 32 with a target hydrogen ion concentration can be prepared by mixing multiple reference sucrose solutions with different hydrogen ion concentrations, and a density gradient liquid with a target hydrogen ion concentration can be prepared in the measurement cell C using these solutions. This allows for the efficient preparation of multiple density gradient liquids with different hydrogen ion concentrations. In other words, using this density gradient liquid preparation apparatus 100, the user does not need to individually prepare the first sucrose solution 31 and the second sucrose solution 32 by adjusting their hydrogen ion concentrations according to the hydrogen ion concentration of the density gradient liquid to be prepared. Instead, by preparing at least two reference sucrose solutions with different hydrogen ion concentrations for preparing the first sucrose solution 31 and the second sucrose solution 32, the user can prepare a density gradient liquid of any desired hydrogen ion concentration using these solutions. This allows for the efficient preparation of multiple density gradient liquids with different hydrogen ion concentrations.

[0047] However, the present invention is not limited to the embodiments described above.

[0048] For example, in the density gradient liquid preparation apparatus 100 of the above embodiment, the first sucrose solution 31 and the second sucrose solution 32 prepared by the first solution preparation unit 1 and the second solution preparation unit 2 are temporarily stored in a container provided by the mixed solution preparation unit 3, and then drawn out by secondary pumps 33a and 33b to prepare a mixed solution, but the apparatus is not limited to this. In other embodiments of the density gradient liquid preparation apparatus 100, as shown in Figure 4, the primary mixing units 13 and 23 provided by the first solution preparation unit 1 and the second solution preparation unit 2 may be configured to directly supply the prepared first sucrose solution 31 and the second sucrose solution 32 to the secondary pumps 33a and 33b provided by the mixed solution preparation unit 3. In this case, the mixed solution preparation unit 3 may not be equipped with secondary pumps 33a and 33b, and the first sucrose solution 31 and the second sucrose solution 32 prepared in the respective primary mixing units 13 and 23 may be directly supplied to the respective secondary branch channels 341a and 341b without going through the secondary pumps 33a and 33b.

[0049] In another embodiment, the density gradient liquid preparation apparatus 100 may be configured to acquire the hydrogen ion concentration value of each reference sucrose solution and the target hydrogen ion concentration value based on user input, and to control the primary pumps 12 and 22 based on these acquired hydrogen ion concentration values ​​of each reference sucrose solution and the target hydrogen ion concentration value. In this case, the control unit 4 may further function as a reference hydrogen ion concentration value acquisition unit 47, which acquires the respective hydrogen ion concentration values ​​of the first reference sucrose solutions 11a and 11b and the second reference sucrose solutions 21a and 21b, as shown in Figure 5.

[0050] Furthermore, while the density gradient liquid preparation apparatus 100 of the above embodiment received a target hydrogen ion concentration value from the user and prepared a density gradient liquid with the target hydrogen ion concentration, it is not limited to this. In other embodiments, it may be configured to receive a target pH value from the user and prepare a density gradient liquid with that target pH value.

[0051] Furthermore, while the density gradient liquid preparation apparatus 100 of the above embodiment prepares a density gradient liquid with a target hydrogen ion concentration, with hydrogen ions as the aggregation-inhibiting component, it is not limited to this. In other embodiments of the density gradient liquid preparation apparatus 100, the aggregation-inhibiting component may be a surfactant, and it may prepare a density gradient liquid containing a predetermined target concentration of surfactant. In this case, the first solution preparation unit 1 and the second solution preparation unit 2 may prepare the first sucrose solution 31 and the second sucrose solution 32 by mixing a plurality of reference sucrose solutions with known surfactant concentrations and densities.

[0052] Furthermore, although the density gradient liquid in the above embodiment was composed of a sucrose solution, it is not limited to this. In other embodiments, the density gradient liquid may be composed of other solutions, such as halocarbons.

[0053] The density gradient liquid preparation apparatus 100 in the above embodiment was used together with the particle size distribution measuring apparatus 200, but it is not limited to this and may be used alone. Also, the measuring cell C is not limited to a cuvette cell and may be of other types.

[0054] In the above embodiment, the pumps provided in the first solution preparation unit 1, the second solution preparation unit 2, and the mixed solution preparation unit 3 were micropumps capable of delivering small amounts of liquid, but they are not limited to this and may be of other types.

[0055] In the above embodiment, the two types of standard sucrose solutions mixed in the first solution preparation unit 1 and the second solution preparation unit 2 were one acidic and the other alkaline, but are not limited to this. In other embodiments, the standard sucrose solutions mixed in the first solution preparation unit 1 and the second solution preparation unit 2 may be acidic, neutral, or alkaline, as long as they have different hydrogen ion concentrations.

[0056] Furthermore, in the above embodiment, multiple reference sucrose solutions of equal density were mixed in the first solution preparation unit 1 and the second solution preparation unit 2, but this is not limited to this. In other embodiments, the first sucrose solution 31 and the second sucrose solution 32 may be prepared by mixing multiple reference sucrose solutions of different densities in the first solution preparation unit 1 and the second solution preparation unit 2, respectively.

[0057] Furthermore, in the above embodiment, the first solution preparation unit 1, the second solution preparation unit 2, the mixed solution preparation unit 3, and the control unit 4 were provided in a single device, but this is not limited to that. In other embodiments, they may be provided in separate devices.

[0058] Furthermore, it goes without saying that the present invention is not limited to the embodiments described above, and various modifications are possible without departing from its spirit. [Industrial applicability]

[0059] According to the density gradient liquid preparation apparatus of the present invention described above, multiple density gradient liquids with different concentrations of aggregation-inhibiting components can be efficiently prepared.

Claims

1. This method involves creating a density gradient liquid in a measuring cell for a centrifugal sedimentation type particle size distribution analyzer. A first solution preparation unit mixes multiple first reference solutions having different concentrations of aggregation-inhibiting components that suppress particle aggregation, to prepare a first solution that has a predetermined target concentration and a first density. A second solution preparation unit mixes a plurality of second reference solutions having different concentrations of the aggregation-inhibiting component to prepare a second solution having the target concentration and a second density different from the first density, A density gradient liquid preparation apparatus comprising a mixed solution preparation unit that mixes the first solution and the second solution to produce a mixed solution of the target concentration, and supplies the mixed solution to the measuring cell with a changed density.

2. The first solution preparation unit prepares the first solution by mixing a plurality of first reference solutions having equal densities. The density gradient liquid preparation apparatus according to claim 1, wherein the second solution preparation unit prepares the second solution by mixing a plurality of the second reference solutions having equal densities.

3. The density gradient liquid preparation apparatus according to claim 1 or 2, wherein the aggregation-inhibiting component is at least one of hydrogen ions or a surfactant.

4. The aggregation-inhibiting component is a hydrogen ion, The first solution preparation unit prepares the first solution by mixing the acidic first standard solution and the alkaline first standard solution. The density gradient liquid preparation apparatus according to claim 3, wherein the second solution preparation unit prepares the second solution by mixing the acidic second standard solution and the alkaline second standard solution.

5. The first solution preparation unit and the second solution preparation unit each, Multiple primary pumps for each of the multiple reference solutions, The system includes a primary mixing unit that mixes the reference solution supplied from each of the primary pumps, The density gradient liquid preparation apparatus according to any one of claims 1 to 4, wherein the solution having a desired concentration of coagulation-inhibiting component is prepared by changing the ratio of the liquid flow rates of each primary pump.

6. A target concentration acquisition unit that obtains the value of the target concentration from the user, The density gradient liquid preparation apparatus according to claim 5, further comprising a primary pump control unit that controls the rotation speed of the primary pumps provided in the first solution preparation unit and the second solution preparation unit, respectively, according to the acquired target concentration value.

7. The mixed solution preparation unit, Two secondary pumps for delivering the first solution and the second solution, The system includes a secondary mixing unit that mixes the first solution and the second solution supplied from each of the secondary pumps, The density gradient liquid preparation apparatus according to any one of claims 1 to 6, wherein the density of the mixed solution produced is changed by changing the ratio of the liquid flow rates of each of the secondary pumps.

8. A cell capacity acquisition unit that obtains the capacity of the measurement cell from the user, The density gradient liquid preparation apparatus according to claim 7, further comprising a secondary pump control unit that controls the rotation speed of each secondary pump according to the acquired capacity of the measurement cell.

9. The density gradient liquid preparation apparatus according to claim 7 or 8, referencing claim 5 or 6, wherein the primary pump and the secondary pump are micropumps.

10. A method for preparing a density gradient liquid in a measuring cell for a centrifugal sedimentation type particle size distribution analyzer, A first solution preparation step involves mixing multiple first reference solutions having different concentrations of aggregation-inhibiting components that suppress particle aggregation, to prepare a first solution that has a predetermined target concentration and a first density. A second solution preparation step involves mixing a plurality of second reference solutions having different concentrations of the aggregation-inhibiting component to prepare a second solution having the target concentration and a second density different from the first density, A method for producing a density gradient liquid, comprising a mixed solution preparation step of mixing the first solution and the second solution to produce a mixed solution of the target concentration, and supplying the mixed solution to the measuring cell with a changed density.

11. A density gradient liquid preparation apparatus according to any one of claims 1 to 9, A particle size distribution measurement system comprising a centrifugal sedimentation type particle size distribution measuring device that performs particle size distribution measurement using the line start method with respect to the density gradient liquid prepared by the density gradient liquid preparation device.

12. A particle size distribution measurement method that uses a density gradient liquid prepared by the density gradient liquid preparation method described in claim 10 and a centrifugal sedimentation type particle size distribution measuring device to measure the particle size distribution by the line start method.

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