How to design a platelet production device

Abstract

Provided is a method for designing a large-scale platelet production device that uses reciprocating agitating blades, whereby the platelet production efficiency is not reduced by enlarging the size of the small-scale production device so as to satisfy geometric similarity conditions based on the shape of the small-scale production device. [Solution] The design method of a platelet manufacturing apparatus of the present invention is characterized in that, when designing a new mixing device with a specified production capacity greater than a specified range, which is mixed with a reciprocating mixing blade 3, based on the shape of the basic mixing device having a production capacity within a specified range designed to achieve a specified platelet production efficiency, the shape of the new mixing device is designed to be larger than the shape of the basic mixing device so as to satisfy the geometric similarity condition, and a new mixing blade 4 is designed to be added above the mixing blade provided on the basic mixing device.

Description

[Technical field]

[0001] The present invention relates to a method for designing a platelet manufacturing apparatus (production apparatus), and in particular to a method for designing a large-scale platelet manufacturing apparatus (agitation apparatus) using a reciprocating agitator blade, with the production capacity scaled up based on a small-scale manufacturing apparatus. [Background technology]

[0002] (1. Description of a conventional platelet manufacturing device)

[0003] A method for manufacturing (producing) platelets from cultured megakaryocytes has been developed, and it has been found that the platelet production efficiency (or platelet count) can be increased by culturing megakaryocytes while stirring the culture solution by reciprocating an impeller placed in a culture vessel.

[0004] Furthermore, in the culture of megakaryocytes, the turbulent energy and shear stress within the culture vessel are of great importance, and the number and shape of the reciprocating agitator blades, as well as their fixed position relative to the drive shaft, are set so that these turbulent energies become predetermined turbulent energies that result in optimal platelet production efficiency.

[0005] For example, Fig. 5 shows a reciprocating stirring device designed to increase the production efficiency of platelets. 1 is, for example, a cylindrical culture vessel with a bottom, 2 is a reciprocating drive shaft vertically or horizontally installed in the culture vessel, and 3 is a single reciprocating stirring blade or blades provided on the drive shaft 2 at a predetermined distance apart in multiple stages.

[0006] The drive shaft 2 is provided so as to be reciprocated in an axial direction, for example, in a vertical direction or a horizontal direction, by a reciprocating drive device (not shown).

[0007] The shape of each of the stirring blades 3 is not particularly limited, but may be made of various shapes such as circular, elliptical, rectangular, etc., and in addition to flat plate-shaped plates, there are also plate-shaped plates that are bent halfway.

[0008] Further, each of the agitating blades 3 may be provided so that its surface is perpendicular to the reciprocating direction of the drive shaft 2, or may be provided so as to be inclined at a predetermined angle.

[0009] Furthermore, the agitating blade 3 may have one or more openings formed therein.

[0010] (2. How to design a large-scale mixing device from a small-scale mixing device)

[0011] Furthermore, when designing (manufacturing) an agitator to increase production capacity (scale up), in addition to a method of designing a new device, for example, the shape of a small-scale agitator set to increase platelet production efficiency can be designed to be larger so as to satisfy the geometric similarity condition, thereby making it possible to maintain the same platelet production efficiency as a small-scale agitator even in a large-scale agitator vessel.

[0012] That is, for example, the shape of the agitator, for example, the shape (including size) of the culture vessel and the shape of the agitator means (the number and shape (including size) of the agitator blades, and the fixed position relative to the drive shaft, etc.) are designed so that the agitator has a small production capacity of, for example, 500 mL of the culture vessel, and has an optimal platelet production efficiency as desired.

[0013] In addition, a mixing device with a small production capacity of 500 mL that has been designed and used in the past with the desired optimum platelet production efficiency may be used.

[0014] When the production capacity is increased from 500 mL, the shape of the 500 mL stirring device can be enlarged so as to satisfy the geometric similarity condition, thereby making it possible to maintain the desired optimal platelet production efficiency, thereby facilitating the scale-up of the platelet production apparatus.

[0015] For example, methods for producing platelets are disclosed in Patent Documents 1 and 2. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] Patent No. 6856537 [Patent Document 2] Patent No. 7153276 Summary of the Invention [Problem to be solved by the invention]

[0017] However, for example, when the production capacity of the culture vessel at the laboratory level was 500 mL to 3 L, the desired optimal platelet production efficiency could be maintained under geometric scale conditions by enlarging the shape of the stirring device, for example, the shape of the culture vessel and the shape of the stirring means, etc. However, when the capacity required for practical use was 8 L or more, 10 L or more, or 45 L or more, a decrease in platelet production efficiency was confirmed although functionality was maintained.

[0018] In order to find the cause, the inventors of the present application used CFD simulation to compare scale-up factors during scale-up in bioreactors.

[0019] In other words, based on a mixer with a production capacity of 2.4 L (VerMES3) designed with the shape of the culture vessel (cylindrical vessel with a bottom) and the shape of the mixing means (two tiers of elliptical mixing blades spaced apart by a desired distance) that would optimize the desired platelet production efficiency, the flow pattern, turbulence energy, and shear stress states were simulated in a mixer with a production capacity of 8 L (VerMES10) and a mixer with a production capacity of 45 L (VerMES50), which were enlarged under geometric similarity conditions.

[0020] As a result, when a mixing device with a production capacity of 2.4 L was scaled up under the geometric similarity conditions as described above, as shown in Figure 6 showing the flow patterns, when the production capacity was 8 L and 45 L, a part A where the flow stagnates was generated in the upper part of the tank, and moreover, it was found that the part where the flow stagnates increases in the upper part of the tank as the production capacity increases.

[0021] As shown in Figures 7 and 10, which show the turbulent energy, the turbulent energy was roughly consistent regardless of the production capacity when the liquid level was between 60% and 70%. However, at levels above 60% or 70%, there was an area A in the upper part of the tank where the turbulent energy was significantly lower for production capacities of 8 L and 45 L compared to when the production capacity was 2.4 L. Moreover, it was found that as the production capacity increased, the area in the upper part of the tank where the turbulent energy was lower increased.

[0022] Furthermore, as shown in Figures 8 and 9, which show the shear stress, the shear stress is roughly consistent regardless of the production capacity up to a liquid level of about 60% to 70%. However, at levels above 60% or 70%, a region A appears in the upper part of the tank where the shear stress is significantly lower for production capacities of 8 L and 45 L compared to when the production capacity is 2.4 L. Moreover, it was found that as the production capacity increases, the region where the shear stress decreases increases in the upper part of the tank.

[0023] From the above, it was found that when the production capacity exceeds a certain size, the volume of the upper part of the vessel, where the shear stress and turbulent energy are low, which are essential for platelet production, increases according to the scale.

[0024] This region represents a loss in production volume, and as a result, the amount of platelet production decreases as the scale is increased. Therefore, there is a need for a device that can apply the physical stress necessary for platelet production to this region regardless of scale.

[0025] The present invention is based on the above findings. [Means for solving the problem]

[0026] In order to achieve the above object, the method for designing a platelet production apparatus of the present invention is to, based on the shape of a basic agitator having a production capacity within a predetermined range designed to achieve a predetermined platelet production efficiency, design a new agitator having a production capacity larger than the predetermined range, which is agitated by a reciprocating agitator impeller, by designing the shape of the new agitator to be larger based on the shape of the basic agitator so as to satisfy a geometric similarity condition, and to add a new agitator impeller above the agitator impeller provided on the basic agitator. The shape of the stirring device is determined by the shape of the culture vessel, the shape of the reciprocating stirring blade of the stirring means consisting of a drive shaft and a reciprocating stirring blade fixed to the drive shaft, and the position of the reciprocating stirring blade fixed to the drive shaft. It is characterized by the above.

[0030] In addition, within the above-mentioned range More than The production capacity of The above Prescribed Within range Based on the shape of a small-scale mixing device with production capacity, the geometric similarity conditions are met. , which is greater than the production capacity of the small-scale mixing device Large-scale mixing equipment multiple, design The small-scale mixing device and each of the Turbulence energy versus liquid level for large-scale mixing equipment Value of , or shear stress The production capacity of the large-scale mixing device is determined when the value of the two is compared and the deviation exceeds a specified amount or exceeds a specified deviation rate. The present invention is characterized in that the above-mentioned is set as follows.

[0031] The production capacity within the predetermined range is greater than 0 L and equal to or less than 3 L, and the production capacity greater than the predetermined range is equal to or greater than 8 L.

[0032] The additional impeller is characterized in that it is an elliptical or rectangular impeller fixed to the drive shaft so as to cross the impeller below it.

[0033] The additional impeller is also characterized in that the direction of the major axis of the additional impeller crosses the direction of the major axis of the impeller below it within a predetermined range.

[0034] Furthermore, when multiple agitating blades are added, the direction of the long diameter of each of the added agitating blades is arranged so as to intersect within a predetermined range with respect to the direction of the long diameter of the agitating blade below it.

[0035] In addition, when the basic stirring device has multiple stirring blades, the direction of the long diameter of each stirring blade except for the lowest stirring blade is arranged to intersect within a predetermined range with respect to the direction of the long diameter of the stirring blade below, and the direction of the long diameter of the additional stirring blade is arranged to intersect within a predetermined range with respect to the direction of the long diameter of the stirring blade below it.

[0036] In addition, when the basic stirring device has multiple stirring blades, the direction of the long diameter of each stirring blade except the lowest stirring blade is arranged to intersect with the direction of the long diameter of the stirring blade below within a predetermined range, and when the additional stirring blades are multiple, the direction of the long diameter of each added stirring blade is arranged to intersect with the direction of the long diameter of the stirring blade below within a predetermined range.

[0037] The predetermined range is 10° to 170°.

[0038] The diameter of the impeller added above is characterized in that it is the same as or larger than the diameter of the impeller below the impeller being added.

[0039] In addition, when an impeller is added to the basic mixing device that is a two-stage impeller, the diameter of the impeller between the added impeller and the lowest impeller is set to the diameter of the added impeller. The range is 100 to 50%. Or, the diameter of the stirring blade at the lowest stage is in the range of 100 to 50%. Ta It is characterized by: Effect of the Invention

[0040] According to the present invention, there is an advantage that a large-scale culture apparatus can be designed based on the shape of a small-scale culture apparatus while maintaining optimal platelet production efficiency.

[0041] In addition, when designing a mixing apparatus with a practical large-scale production capacity, there is no need to redesign it from scratch, but rather, there is an advantage in that a large-scale mixing apparatus can be designed simply by enlarging it based on the shape of a small-scale mixing apparatus under geometric similarity conditions and adding mixing blades. [Brief description of the drawings]

[0042] [Figure 1] FIG. 1 is an explanatory diagram of a method for designing an apparatus for producing platelets of the present invention. [Diagram 2] FIG. 13 is a diagram showing the relationship between the liquid level and the turbulence energy when the number of stirring blades and the production capacity are changed. [Diagram 3] FIG. 13 is a diagram showing the relationship between the liquid level and the shear stress when the number of stirring blades and the production capacity are changed. [Figure 4] FIG. 2 is a cross-sectional view for explaining a method for designing the platelet production apparatus of the present invention. [Diagram 5] FIG. 1 is an explanatory diagram of a conventional method for designing a platelet production device. [Figure 6] FIG. 1 is a diagram showing flow patterns of various mixing devices designed in the past. [Figure 7] FIG. 1 is a diagram showing turbulent energy in a culture apparatus of each of the conventionally designed stirring devices. [Figure 8] FIG. 1 is a diagram showing the shear stress in the culture apparatus of each of the conventionally designed stirring devices. [Figure 9] FIG. 1 is a diagram showing the relationship between the liquid level and the shear stress of each of the conventionally designed mixing devices. [Figure 10] FIG. 1 is a diagram showing the relationship between the liquid level and turbulent energy of each of the conventionally designed mixing devices. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0043] Examples of modes for carrying out the present invention are given below. EXAMPLES

[0044] A first embodiment of the present invention will be described with reference to Figures 1 to 4. Note that the same parts as those in the conventional description are given the same reference numerals and the description thereof will be omitted.

[0045] (3. Description of Overall Structure)

[0046] As a result of various experiments, it was found that when a large-scale platelet production apparatus is designed based on a small-scale agitator, and the production capacity of the large-scale agitator is in the laboratory level range of 3 L or less, the optimal platelet production efficiency can be maintained by designing the small-scale designed shape of the agitator (e.g., the shape of the culture vessel and the shape of the agitator means) to be larger so as to satisfy the geometric similarity condition, so that the optimal platelet production efficiency can be maintained.

[0047] However, for example, when designing a culture apparatus for a production vessel exceeding 3L (large scale), for example, 8L or more, 10L or more, or 45L or more, which are practical levels, based on the shape of an agitator with a production capacity of 3L or less (small scale), in the present invention, the shape of the agitator designed for the small scale (for example, the shape of the culture vessel and the shape of the agitator means) that can optimize the platelet production efficiency as desired is set, and the size is increased under geometric similarity conditions. Furthermore, as shown in Figure 1, an additional reciprocating agitator blade 4 is fixed to the drive shaft 2 above the uppermost agitator blade 3 of the agitator 1 for the small scale, thereby compensating for the reduced turbulent energy and shear stress and optimizing the platelet production efficiency (platelet count).

[0048] The number of the additional stirring blades 4 may be one or more.

[0049] The position where the stirring blade 4 is added to the drive shaft 2 is preferably fixed at a location above the liquid level where the deviation rate described later becomes high, for example, at a location where the liquid level is 60% or 70% or higher.

[0050] Figure 2 shows the relationship between liquid level and shear stress, using CFD simulation, in an agitator with a production capacity of 2.4 L using a two-stage agitator impeller, an agitator with a production capacity of 8 L that is enlarged based on the shape of the 2.4 L agitator so as to satisfy the geometric similarity condition, an agitator with a production capacity of 45 L, and a culture apparatus with a production capacity of 45 L and a three-stage impeller with an additional agitator impeller 4 on top.

[0051] As can be seen from Figure 2, in the case of a mixing device with a production capacity of 45 L and two-stage impellers, the shear stress is significantly reduced when the liquid level is 60% to 70% or higher, compared to the shear stress of a small-scale culture device with a production capacity of 2.4 L and two-stage impellers. However, by using three-stage impellers, the shear stress can be restored to approximately the same level as that of a small-scale culture device with a production capacity of 2.4 L, despite the large-scale culture device with a production capacity of 45 L.

[0052] FIG. 3 is a diagram showing the relationship between the liquid level and turbulence energy in a 2.4 L production capacity agitator using a two-stage impeller, an 8 L production capacity agitator that is enlarged based on the shape of the 2.4 L agitator so as to satisfy the geometric similarity condition, an 45 L production capacity agitator, and a 45 L production capacity culture apparatus with a three-stage impeller with an additional impeller on top, using CFD simulation.

[0053] In this case, as with shear stress, in comparison with the turbulent energy of a culture apparatus with a production capacity of 2.4 L and two-stage impeller, in the case of a production capacity of 45 L and two-stage impeller, the turbulent energy is significantly reduced when the liquid level is 60% to 70% or more. However, by using three-stage impellers, it is found that the shear stress can be restored to approximately the same level.

[0054] In addition, as long as each of the agitating blades is a reciprocating agitating blade, there are no particular limitations on the shape, etc., and there are various shapes of plate bodies, such as circular, elliptical, rectangular, etc., as well as plate bodies that are entirely flat and plate bodies that are bent in the middle.

[0055] In addition, as to the production capacity below which a scaled-up mixing device can be designed based only on the geometric similarity condition, and the production capacity above which a mixing impeller should be added, for example, based on the shape of a mixing device that can optimize the platelet production efficiency at a certain scale, multiple mixing devices of a scale larger than the certain scale are designed so as to satisfy the geometric similarity condition, and the mixing device of the certain scale (hereinafter referred to as "small scale") and each mixing device of a scale larger than the certain scale (hereinafter referred to as "large scale") are experimentally or simulated to obtain flow diagrams, turbulent energy values, and shear stress values ​​for the liquid levels of each mixing device, and from the obtained diagrams, values, etc., it is determined, for example, when a predetermined amount has dissociated (or a predetermined dissociation rate has been reached), that a production capacity below that is designed based only on the geometric similarity condition, and that a mixing impeller should be added for a production capacity above that (or larger).

[0056] When the deviation rate or the like is equal to or greater than a predetermined value, two or three or more stirring blades may be added as necessary.

[0057] For example, when the production capacity of a large-scale mixing device is greater than 0 L and less than 3 L, it is designed based only on geometric similarity conditions.

[0058] In addition, when the production capacity of the small-scale mixing equipment is 3 L or less and the production capacity of the large-scale mixing equipment is 8 L or more, 10 L or more, or 45 L or more, the mixing equipment is designed to have an additional mixing blade.

[0059] In addition, when successively designing larger-scale agitation apparatuses, such as designing a medium-scale agitation apparatus with a larger production capacity based on a small-scale agitation apparatus and then designing a large-scale agitation apparatus with an even larger production capacity based on this designed medium-scale agitation apparatus, in addition to designing based on the agitation apparatus immediately preceding it, it is also possible to design the agitation apparatus based on the agitation apparatus designed before the immediately preceding agitation apparatus.

[0060] That is, for example, when a small-scale agitator has a production capacity of 3 L or less and a large-scale agitator has a production capacity of 5 L, if a large-scale agitator with a larger production capacity, for example, 8 L or more, is designed based on this 5 L agitator, it may be designed based on the 5 L agitator, or it may be designed based on a small-scale agitator of 3 L or less that serves as the basis for the design of the 5 L agitator.

[0061] (4. Description of the mixing blades to be added)

[0062] Furthermore, it is preferable that the additional agitator blades are arranged so as not to impede the circulating flow at the top of the liquid contained in the culture vessel, and that the elliptical or rectangular blades are arranged so that their long diameters intersect, for example at right angles, with the long diameter of the agitator blade below them.

[0063] That is, for example, it is preferable to design the impellers 3 and 4 of each stage to be elliptical (excluding circular) or rectangular, and to arrange the impeller 4 so that the direction of the major axis 4a of the impeller 4 to be added is within a predetermined range θ relative to the direction of the major axis 3a of the impeller 3 below, as shown in Figure 4.

[0064] The specified range θ is an angle range that does not overlap with the stirring blade below (e.g., the tip of the stirring blade), and is, for example, 10° to 170°, preferably 45° to 135°, more preferably 80° to 100°, and even more preferably 90°.

[0065] When a plurality of stirring blades are added, it is preferable that each stirring blade is designed to satisfy the above-mentioned conditions.

[0066] As described above, by providing the impeller out of phase with the impeller below, the pressure balance is disrupted and an upward flow is easily formed, preventing the circulating flow from being impeded. This makes it possible to maintain optimal platelet production efficiency in the large-scale mixer designed based on a small-scale mixer.

[0067] Furthermore, if the impellers of each stage of a small-scale agitator, which is the basis for the design of a large-scale agitator, are also arranged within the predetermined range θ, it will be possible to maintain optimal platelet production efficiency in the large-scale agitator designed based on the small-scale agitator.

[0068] In addition, the blade diameter of the added stirring blade is adjusted so as to obtain an appropriate physical stress.

[0069] That is, although it differs depending on the production purpose, the ratio of the blade diameter d to the vessel diameter D is preferably within the range of D / d=0.95 to 0.5.

[0070] In addition, it is desirable that the diameter, for example the major axis, of the impeller added above is the same as or larger than the diameter, for example the major axis, of the impeller below it.

[0071] For example, when a large-scale stirring device has three impellers, it is desirable that the diameter, for example the major axis, of the uppermost impeller be the same as or larger than the diameter, for example the major axis, of the intermediate impeller below it.

[0072] Furthermore, when a large-scale stirring device has three-stage impellers, the diameter of the intermediate impeller between the topmost impeller and the bottommost impeller, for example, the major axis, is preferably in the range of 100 to 50% of the diameter of the topmost impeller, for example, the major axis, and the diameter of the bottommost impeller, for example, the major axis, respectively, and is preferably the same diameter or slightly smaller.

[0073] As a result, the circulating flow of the liquid in the tank is not hindered, and optimal platelet production efficiency can be maintained in the large-scale mixing device designed based on a small-scale mixing device.

[0074] (5. Effects of the present invention)

[0075] According to the present invention, when the production capacity of the culture vessel is within a range below a predetermined value, a scaled-up stirring apparatus can be designed based on the shape of the basic culture apparatus simply by satisfying the geometric similarity conditions. Furthermore, when the production capacity exceeds a predetermined value, for example, greater than 3 L, or 8 L or more, or 10 L or more, or 45 L or more, it is advantageous that a large-scale culture apparatus can be designed based on the shape of the culture vessel of a small-scale stirring apparatus by satisfying the geometric similarity conditions and further adding an agitator blade to the upper stage.

[0076] Furthermore, by setting the added mixing blades to a specified position and size, it becomes easier to form an upward flow, etc., and in a large-scale mixing apparatus designed based on a small-scale mixing apparatus, it becomes possible to maintain the same optimal platelet production efficiency as in the small-scale apparatus. [Explanation of symbols]

[0077] 1 Culture vessel 2 Drive shaft 3 Reciprocating stirring blade 3a Major axis 4 additional reciprocating impellers 4a Major axis

Claims

1. Based on the shape of the mixing device that is the basis of the production capacity within a predetermined range designed to have a predetermined platelet production efficiency, which is mixed by a reciprocating mixing blade, When designing a new mixing device with a predetermined production capacity larger than the predetermined range, which is mixed by a reciprocating mixing blade, Based on the shape of the basic mixing device, the shape of the new mixing device is designed to be larger so as to satisfy a geometric similarity condition, A new stirring blade is added above the stirring blade provided on the basic stirring device, a reciprocating agitator blade fixed to a drive shaft; and a shape of the agitator that is determined by the shape of the culture vessel, the shape of the reciprocating agitator blade of a stirring means that is composed of a drive shaft and a reciprocating agitator blade fixed to the drive shaft, and the position of the reciprocating agitator blade fixed to the drive shaft.

2. The predetermined production capacity greater than the predetermined range is Based on the shape of the small-scale mixing device having a production capacity within the predetermined range, a plurality of large-scale mixing devices having a production capacity larger than that of the small-scale mixing device are designed so as to satisfy a geometric similarity condition; 2. The method for designing a platelet production apparatus according to claim 1, characterized in that a value of turbulent energy or a value of shear stress for liquid levels in the small-scale agitator and each of the large-scale agitators is compared, and the production capacity of the large-scale agitator is set when the value of the turbulent energy or the value of the shear stress for liquid levels in the small-scale agitator deviates by a predetermined amount or more, or when the value of the turbulent energy or the value of shear stress for liquid levels in the small-scale agitator deviates by a predetermined amount or more, or when the value of the turbulent energy or the value of shear stress for liquid levels in each of the large-scale agitators ... turbulent energy or the value of shear stress for liquid levels in each of the large-scale agitators deviates by a predetermined amount or more, or when the turbulent energy or the value of shear stress for liquid levels in each of the large-scale agitator deviates by a predetermined amount or more, or when the turbulent energy or the value of shear stress for liquid levels in each of the large-scale agitator deviates by a predetermined amount or more.

3. The production volume within the predetermined range is greater than 0 L and less than or equal to 3 L, 2. The method for designing an apparatus for producing platelets according to claim 1, wherein the predetermined production volume which is greater than the predetermined range is 8 L or more.

4. 2. The method for designing a platelet production apparatus according to claim 1, wherein the additional agitating blade is an elliptical blade or a rectangular blade fixed to the drive shaft so as to cross the agitating blade below it.

5. 2. The method for designing a platelet production apparatus according to claim 1, wherein the direction of the major axis of the additional impeller is set to intersect within a predetermined range with the direction of the major axis of the impeller below it.

6. 2. The method for designing a platelet production apparatus according to claim 1, characterized in that, when a plurality of agitating blades are added, the direction of the major axis of each of the added agitating blades is arranged to intersect within a predetermined range with respect to the direction of the major axis of the agitating blade below it.

7. In the case where the stirring blades of the basic stirring device are multiple, the direction of the major axis of each stirring blade except for the lowest stirring blade is arranged to cross the direction of the major axis of the lower stirring blade within a predetermined range, 2. The method for designing a platelet production apparatus according to claim 1, wherein the direction of the major axis of the additional impeller is arranged to intersect within a predetermined range with the direction of the major axis of the impeller below it.

8. In the case where the stirring blades of the basic stirring device are multiple, the direction of the major axis of each stirring blade except for the lowest stirring blade is arranged to cross the direction of the major axis of the lower stirring blade within a predetermined range, 2. The method for designing a platelet production apparatus according to claim 1, characterized in that, when a plurality of agitating blades are added, the direction of the major axis of each of the added agitating blades is arranged to intersect within a predetermined range with respect to the direction of the major axis of the agitating blade below it.

9. 9. The method for designing an apparatus for producing platelets according to claim 5, wherein the predetermined range is 10° to 170°.

10. 2. The method for designing an apparatus for producing platelets according to claim 1, wherein the diameter of the impeller added above is equal to or larger than the diameter of the impeller below the added impeller.

11. 2. The method for designing an apparatus for producing platelets according to claim 1, characterized in that, when an impeller is added to a basic mixing device which is a two-stage impeller, the diameter of the impeller between the added impeller and the impeller at the lowest stage is in the range of 100 to 50% of the diameter of the added impeller, or in the range of 100 to 50% of the diameter of the impeller at the lowest stage.

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