Static mixer

Abstract

A static mixing apparatus for mixing a fluid, preferably a liquid is provided. The mixer comprises a plurality of chambers in series, the first chamber of the series comprising a fluid inlet, and the final chamber of the series comprising a fluid outlet, each chamber except the final chamber including orifices defining a flow path from the fluid inlet and into each chamber in series and to the fluid outlet and the final chamber including a gas outlet located at the opposite end of the static mixing apparatus to the fluid inlet and fluid outlet.

Claims

1. A static mixing apparatus for mixing a fluid, comprising a housing having end plates and a sidewall, a plurality of chambers in series within the housing, wherein the plurality of chambers comprises an innermost chamber of the series comprising a chamber wall and a fluid inlet, a second chamber formed from the chamber wall of the innermost chamber and an outer chamber wall, an optional subsequent chamber formed from the outer chamber wall of a prior chamber and an outer chamber wall, and an outermost chamber of the series formed from an outer chamber wall of a prior chamber in series and the sidewall of the housing and comprising a fluid outlet, each chamber wall except the outermost chamber including orifices defining a flow path from the fluid inlet and into each chamber in series and to the fluid outlet, wherein the outermost chamber further comprises a gas outlet located at the opposite end of the static mixing apparatus to the fluid inlet and fluid outlet.

2. The mixing apparatus according to claim 1, wherein each chamber of the plurality of chambers in series is concentric and of circular cross section.

3. The mixing apparatus according to claim 1, which comprises an even number of chambers.

4. The mixing apparatus according to claim 1, wherein the combined area of all orifices and any additional chamber exits within the chamber wall separating any two of the plurality of chambers is greater than the area of the fluid inlet.

5. The mixing apparatus according to claim 4, wherein the inlet and outlet are located at a base of the mixing apparatus.

6. The mixing apparatus according to claim 1, wherein the fluid inlet is located at a base of the mixing apparatus, and wherein the area of each orifice in the chamber wall increases along the direction of the chamber wall away from the fluid inlet of the mixing apparatus.

7. The mixing apparatus according to claim 1, comprising an even number of chambers and wherein the direction of flow within each chamber beginning with the fluid inlet alternates with each subsequent chamber.

8. The mixing apparatus according to claim 7, wherein the orifices between adjacent chambers are offset.

9. The mixing apparatus according to claim 1, wherein the fluid inlet and fluid outlet are located at the base of the mixing apparatus, the chamber wall of the second chamber has two initial orifices at a base of the chamber wall of the second chamber.

10. A method for mixing two or more fluids, which comprises passing the fluids through a mixing apparatus according to claim 1.

11. The method according to claim 10, wherein the fluids are aqueous solutions, and the method comprises a step in a bioprocessing operation.

12. The method according to claim 11, wherein the method is comprised in a method for producing a biomolecule.

13. An apparatus for carrying out a bioprocessing operation, the apparatus comprising mixing apparatus according to claim 1.

14. A method for producing a biomolecule which comprises processing the biomolecule in a bioprocessing operation employing apparatus according to claim 13.

15. The mixing apparatus according to claim 1, wherein each chamber is concentric and of circular cross section and wherein the mixing apparatus comprises an even number of chambers.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The present invention is illustrated by reference to FIGS. 1 to 6.

(2) FIG. 1 shows a cross section through a mixer according to the present invention.

(3) FIG. 2 shows a cross section through a mixer according to the present invention.

(4) FIG. 3 provides a graphical representation of the conductivity data obtained in Example 1.

(5) FIG. 4 provides a graphical representation of the conductivity data obtained in Example 2.

(6) FIG. 5 provides a graphical representation of the conductivity data obtained in Example 3.

(7) FIG. 6 provides a graphical representation of the conductivity data obtained in Example 4.

(8) The mixer comprises a housing formed from end plates, 1 and 2, which are preferably circular, and a sidewall, 3, which is preferably cylindrical. Fluid inlet, 4, allows fluid to flow under pressure, into a first chamber, 5, preferably located centrally on end plates 1 and 2. The walls, 6, of the first chamber, 5, are preferably cylindrical and concentric with the sidewall, 3. The walls comprise a series of orifices, 7, dispersed along a direction of flow, the nearest point to the fluid inlet of each subsequent orifice overlapping with at least the furthest point from the fluid inlet of the previous orifice, and being off-set along the direction of flow from the previous orifice. The orifices, 7, allow a portion of the flow path to flow into a second chamber, 8, which is preferably cylindrical, and concentric with the sidewall, 3. The second chamber comprises an inner wall formed by the wall of the first chamber, 6, and an outer wall, 9. The outer wall of the second chamber, 9, comprises a series of orifices, 10, dispersed along a direction of flow, the nearest point to the base plate, 1, of each subsequent orifice overlapping with at least the furthest point from the base plate, 1, of the previous orifice, and includes a plurality of additional chamber exits, 11, ending at the end plate, 1. The orifices, 10 and 11, allow a portion of the flow path to flow into a third chamber, 12, which is preferably cylindrical, and concentric with the sidewall, 3. The third chamber comprises an inner wall formed by the outer wall of the second chamber, 9, and an outer wall, 13. The outer wall of the third chamber, 12, comprises a series of orifices, 14, dispersed along a direction of flow, the start of each subsequent orifice overlapping with at least the end of the previous orifice, and being off-set along the direction of flow from the previous orifice. The orifices, 14, allow a portion of the flow path to flow into a fourth chamber, 15, which comprises an inner wall formed by the outer wall of the third chamber, 13, and the sidewall, 3. The fourth chamber also comprises an outlet, 16, located at the end plate, 1, and a gas release valve, 17, located at the opposite end to the outlet, 16. In use, the mixer is preferable oriented vertically along the axis of chambers 5, 8, 12 and 15, with end plate 1 at the base, and end plate 2 at the top. In use, the principle flow of fluid is away from the end plate, 1, in the first and third chambers, 5 and 12, respectively, and towards the end plate, 1, in the second and fourth chambers, 8 and 15, respectively.

(9) FIG. 2 shows a cross-section perpendicular to the axis of chambers 5, 8, 12 and 15 of a mixer of illustrated in FIG. 1, showing the concentric arrangement of the chambers 5 8, 12 and 15, and the walls of said chambers, 6, 9, 13 and 3. For clarity, the cross-section is shown as a section where no orifices are present in any of the walls of the chambers.

(10) The present invention is illustrated without limitation by the following Examples.

EXAMPLE 1

(11) Abbreviations:

(12) L litre L/h litres per hour min minute mm millimetre s second TC Tri-clover clamp

(13) A solution of 1 M sodium chloride and water for dilution was used in the experimental studies. The mixing chamber was tested on a bioprocessing system as described in application WO2019/158906. The sodium chloride solution was connected to the first inlet and the water was connected to the final inlet, allowing the system to alternately select either inlet. The inlets were connected to a pump through a quaternary valve that was controlled to select either water or a sodium chloride/water mix through repeatedly dosing aliquots of sodium chloride for 1 s and water for 3 s for the duration of the experiment. Downstream of the pump a conductivity sensor monitored the conductivity of the liquid prior to it entering the mixing chamber. A second conductivity sensor downstream of the mixing chamber monitored the final conductivity of the liquid.

(14) The mixing apparatus employed in this experiment used a SpectrumLabs (now Repligen, USA) K06 hollow fibre housing (inner diameter 63 mm, 3 inch TC end, 460 mm long with two 35 mm diameter ports 22.5 mm from each end) with a 3 inch TC blanking plate capping the top and a 3 inch TC base plate with a 15 mm diameter inlet in the centre. The inside of the mixing apparatus was divided into four sections by three circular tubes with a length of 460 mm and increasing diameters. The inner tube, being connected through the base to the inlet of the mixing apparatus, had an internal diameter of 15 mm and a wall thickness of 2.5 mm. The middle tube had an internal diameter of 32 mm and a wall thickness of 2.5 mm. The final, outer, tube had an internal diameter of 50 mm and a wall thickness of 2.5 mm. This resulted in a total internal volume of 1.06 L for the mixing chamber. Each tube contained a spiral of stadium shaped orifices starting at 10 mm above the base, progressing in a clockwise direction, the start of the next orifice was in-line with and therefore slightly overlapping with the previous orifice, but off-set by 90 degrees when viewed along the tube. The length of each orifice increased by 2 mm such that the final orifice was 42 mm long. The orifices on the inner and outer were 4 mm in width and aligned so the shorter, bottom orifice of each tube was facing 180 degrees away from the bottom 35 mm diameter port. The orifices making the spiral on the middle tube had a width of 3 mm and an additional 2 openings were cut into the bottom of the tube. The mid-point of these two openings were at 90 degrees to the shortest, bottom 3 mm wide orifice and each were 10 mm high and 25 mm wide. The middle tube was aligned so that the shortest, bottom orifice faced towards the bottom 35 mm diameter port.

(15) The experiment was initiated with the chamber pre-filled to 150 mm from the bottom with liquid. The pump speed was set to 20% of its maximum output, resulting in an average flow of 225 L/h, and the chamber was flushed with water for 2 min before the sodium chloride was dosed into the water at the 1:4 ratio described for 5 min. The conductivity data was recorded from 3 min into the experiment to allow the chamber to exchange into the sodium chloride mix and then equilibrate. The results of Example 1 are given in FIG. 3 and Table 1.

EXAMPLE 2

(16) The method of Example 1 was repeated, but with the pump speed set to 35% of its maximum output resulting in an average flow of 395 L/h. The results of Example 2 are given in FIG. 4 and Table 1.

EXAMPLE 3

(17) The method of Example 1 was repeated, but with the pump speed set to 50% of its maximum output resulting in an average flow of 560 L/h.

(18) The results of Example 3 are given in FIG. 5 and Table 1.

(19) TABLE-US-00001 TABLE 1 20% pump 35% pump 50% pump speed speed speed (225 L/h) (395 L/h) (560 L/h) Inlet Outlet Inlet Outlet Inlet Outlet Delta of Conductivity 3.41 0.37 6.82 0.45 8.90 0.71 minimum and maximum (mS/cm) Standard Deviation 1.00 0.18 2.13 0.10 2.81 0.16 (mS/cm) Average percent 4.0 0.3 8.6 0.5 12.0 0.9 deviation of minimum and maximum from mean (%) Mixing Chamber ~45 ~55 ~70 volume utilisation (%) Residence time (s) 8 6 5

EXAMPLE 4

(20) Using the mixing chamber and flow path described in Example 1, a conductivity gradient was generated with a 0.23 M sodium chloride solution and water. Using a 4 s duty cycle and the pump speed set to 10% or 20% of maximum output two gradients were run. Each gradient was generated by running from 0 to 100% sodium chloride over 15 min. In practice this required calculating the valve open time ratios between the water and sodium chloride inlets every 4 s. For example, initially the water valve was open for the full 4 s, at 1 min the sodium chloride valve was open for 0.27 s and the water valve was open for 3.73 s, and by 10 min the sodium chloride valve was open for 2.67 s and the water valve was open for 1.33 s. At the end of the gradient the sodium chloride valve was open for the full 4 s. The conductivity of both gradient runs were measured post mixing chamber and are plotted in FIG. 6.

(21) The Examples demonstrate that the mixer of the present invention allows mixing of liquids that are delivered chronologically into the flow path within a specific time period. In most cases, ratios of the liquids are added within a total liquid volume that is less than or equal to the liquid volume within the mixing chamber. For continuous operation, a duty cycle is used to allow repeated, chronological delivery of two or more liquids into the mixer.

(22) In the mixers of the present invention, a surprisingly small hold up volume in the mixer for the range of flow rates employed. Further, the volume of mixer is surprisingly very small compared with the volumes of liquid mixed.

(23) The mixers of the present invention can act both as an apparatus to induce mixing of two or more liquids, and simultaneously as an apparatus for trapping and retaining gas bubbles from the liquid stream.