Static Mixer

Abstract

A static mixing apparatus for mixing a fluid, preferably a liquid is provided. The mixer comprises a plurality of chambers (5, 8, 12, 15) in series, the first chamber (5) of the series comprising a fluid inlet (4), and the final chamber (15) of the series comprising a fluid outlet (16), each chamber other than the final chamber in the series being in fluid connection with a subsequent chamber, the fluid connection comprising a plurality of orifices (7, 10, 11, 14) dispersed along a direction of flow, the nearest point to the fluid inlet of each subsequent orifice to the inlet overlapping with the furthest point from the fluid inlet of the previous orifice, and being off-set along the direction of flow from the previous orifice.

Claims

1. A static mixing apparatus for mixing a fluid, comprising 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 other than the final chamber in the series being in fluid connection with a subsequent chamber, the fluid connection comprising a plurality of orifices dispersed along a direction of flow, the nearest point to the fluid inlet of each subsequent orifice to the inlet overlapping with the furthest point from the fluid inlet of the previous orifice, and being off-set along the direction of flow from the previous orifice.

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

3. The mixing apparatus according to claim 1, wherein the first chamber is the innermost chamber and the final chamber the outermost chamber.

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

5. The mixing apparatus according to claim 1, which comprises a gas outlet located at the opposite end of the mixing apparatus to the inlet and outlet.

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

7. The mixing apparatus according to claim 1, wherein, along the longitudinal direction for a given chamber, the nearest point to the inlet of each subsequent orifice and the furthest point from the inlet of the preceding orifice are aligned such that they are form part of the same cross-section perpendicular to the axis of the chamber of the chamber.

8. The mixing apparatus according to claim 1, wherein the fluid inlet is located at the base of the mixer, and wherein the area of the orifices in the wall of all odd-numbered chambers that are fluidly connected to a subsequent chamber increases along the direction of the chamber away from the inlet end of the mixer.

9. The mixing apparatus according to claim 1, comprising an even number of chambers and wherein the first orifice along the longitudinal direction in the walls of all odd numbered chamber walls that are in fluid connection with a subsequent chamber are aligned such that they are not directed towards the fluid outlet.

10. The mixing apparatus according to claim 10, wherein the first orifice along the longitudinal direction in the walls of all odd numbered chamber walls that are in fluid connection with a subsequent chamber is aligned to be 180 degrees from the direction of the centre center of the fluid outlet.

11. The mixing apparatus according to claim 1, wherein the inlet and outlet are located at the base of the mixer, the chamber wall between the even-numbered chambers and the subsequent odd-numbered chamber has two initial orifices of equal cross-sectional area at the base of the fluid inlet end of the chamber, and wherein the centre center points of the initial orifices are aligned at 180 degrees to each other.

12. The method for mixing two or more fluids, which comprises passing the fluids through a mixer according to claim 1.

13. The method according to claim 12, wherein the fluids are aqueous solutions, and the method comprises a step in a bioprocessing operation.

14. The method according to claim 13, wherein the method is comprised in a method for producing a biomolecule.

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

16. The method for producing a biomolecule which comprises processing the biomolecule in a bioprocessing operation employing apparatus according to claim 15.

17. The mixing apparatus according to claim 6, wherein each chamber is concentric and of circular cross section the first chamber is the innermost chamber and the final chamber the outermost chamber and which comprises an even number of chambers.

Description

EXAMPLE 1

Abbreviations:

[0043] L litre [0044] L/h litres per hour [0045] min minute [0046] mm millimetre [0047] s second [0048] TC Tri-clover clamp

[0049] 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 copending 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.

[0050] 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.

[0051] 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

[0052] 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

[0053] 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. The results of Example 3 are given in FIG. 5 and Table 1.

TABLE-US-00001 TABLE 1 20% pump speed 35% pump speed 50% pump 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 volume ~45 ~55 ~70 utilisation (%) Residence time (s) 8 6 5

EXAMPLE 4

[0054] 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.

[0055] 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.

[0056] 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.

[0057] The mixers of the present invention can act both an apparatus to induce mixing of two or more liquids, and simultaneously an apparatus for trapping and retaining gas bubbles from the liquid stream.