Novel type of extraction cell for a centrifugal partition chromatograph, as well as a centrifugal partition chromatograph containing such an extraction cell

Abstract

The object of the invention relates to an extraction cell (100) used in a centrifugal partition chromatograph, which has a cell wall (120) determining a closed extraction chamber (150), as well as an inlet (115) and an outlet (140) ensuring the fluid connection between the extraction chamber (150) and the space outside of the extraction cell (100) formed on essentially opposite parts of the cell wall (120).

The extraction cell (100) according to the invention is constructed asymmetrically from the point of view of the reversibility of the direction of flow used when the centrifugal partition chromatograph is in operation.

Claims

1. Extraction cell (100, 200) for a centrifugal partition chromatograph, which has a cell wall (120, 220) determining a closed extraction chamber (150, 250), as well as an inlet (115, 215) and an outlet (140, 240) ensuring the fluid connection between the extraction chamber (150, 250) and the space outside of the extraction cell (100, 200) formed on essentially opposite parts of the cell wall (120, 220), characterised by that the extraction cell (100, 200) has an asymmetrical structure from the point of view of reversibility of flow direction used when the centrifugal partition chromatograph is in operation.

2. The extraction cell (100, 200) according to claim 1, characterised by that the inlet (115, 215) and the outlet (140, 240) have different cross-sections.

3. The extraction cell (100, 200) according to claim 1, characterised by that the flow cross-section of the outlet (140, 240) is greater than the flow cross-section of the inlet (115, 215).

4. The extraction cell (100, 200) according to claim 1, characterised by that the inlet (115, 215) is formed as at least one inlet branch (115a, 115b).

5. The extraction cell (100, 200) according to claim 1, characterised by that the cell wall (120, 220) forms an essentially rectangular based inclined prism, the angle of inclination of which, with the extraction cell (100, 200) in its position in the centrifugal partition chromatograph, being selected to minimise the Coriolis force occurring as a result of the rotation when the extraction cell (100, 200) is in its operation state.

6. The extraction cell (100, 200) according to claim 5, characterised by that the angle of tilt is between 5° and 30°, preferably between 15° and 18°.

7. The extraction cell (100, 200) according to claim 1, characterised by that the extraction chamber (150, 250) is connected to the outlet (140, 240) via a collection pool (130, 230).

8. The extraction cell (100) according to claim 7, characterised by that the collection pool (130) is formed as a protruding hemispherical part of the cell wall (120), and the outlet (140) is located on this hemisphere.

9. The extraction cell (100) according to claim 1, characterised by that at least a part of the surface (125) of the cell wall (120) bordering with the extraction chamber (150) is roughened.

10. The extraction cell (100) according to claim 9, characterised by that the roughening is ensured by steps or saw teeth on the surface (125).

11. The extraction cell (100) according to claim 1, characterised by that it is produced using fused deposition modelling 3D printing technology.

12. The extraction cell (200) according to claim 7, characterised by that the collection pool (230) is formed as a part of the cell wall (220) extending in an inclined way in the direction of the outlet (240).

13. The extraction cell (200) according to claim 12, characterised by that it is produced by combining two half cells obtained using CNC milling, where the surfaces of the cell halves touching each other are coated with a fluoropolymer.

14. Centrifugal partition chromatograph, characterised by that it contains at least one extraction cell (100, 200) according to claim 1.

15. Centrifugal partition chromatograph according to claim 14, characterised by that it has a modular construction realised with essentially identical modules (300), where all of the modules (300) contain more than one extraction cell (100, 200) connected by channels (330) providing a fluid connection between them, furthermore the individual modules (300) are connected in series with each other via tubes (430).

Description

[0030] In the following the invention is presented in detail with reference to the attached drawing, where

[0031] FIG. 1 is a block diagram of a CPC assembly used today for performing CPC-based separation procedures, where the arrows represent the flow of the liquid between the components of the assembly and its direction;

[0032] FIG. 2 is a schematic illustration of the operation of the extraction cell used in the CPC rotor unit of the CPC assembly according to FIG. 1;

[0033] FIG. 3 shows the simulated flow pattern in a known extraction cell, which illustrates the damaging back-mixing effect in the cell of the Coriolis force (marked with an arrow);

[0034] FIGS. 4A and 4B are simulated flow patterns, which illustrate how the chromatographic parameters compete with one another in the case of two different cell geometries in use today;

[0035] FIG. 5 shows an example of a preferable embodiment of a new-type asymmetrical CPC extraction cell produced using FDM 3D printing technology in longitudinal cross-section, as well as in a schematic, partially cutaway perspective view;

[0036] FIG. 6 is the top view of the CPC extraction cell illustrated in FIG. 5, viewed from the direction of the arrow indicated in FIG. 5;

[0037] FIGS. 7A and 7B are the simulated (SC/Tetra v11 software package) flow patterns occurring in the CPC extraction cell according to FIG. 5 with different outlet cross-sections (1.7 mm and 2.0 mm; the left hand and right hand image in FIG. 7A respectively), and with different cell axis tilts (16.5° and 20.0°, the left hand and right hand image in FIG. 7B respectively); beside the designated parameter the other parameters used in the simulation remained unchanged in both cases;

[0038] FIG. 8 shows an example of a preferable embodiment of a new-type asymmetrical CPC extraction cell produced using CNC milling in longitudinal cross section as well as in a schematic, perspective view;

[0039] FIG. 9 shows a schematic depiction of a module of a modularly constructed CPC rotor according to the invention containing several CPC extraction cells according to the invention linked closely together; and

[0040] FIG. 10 depicts a large sized (r>300 mm) disc CPC rotor constructed using the CPC rotor modules depicted in FIG. 9 with an annular cross-section.

[0041] Consecutively FIGS. 5 and 6 show an example of a preferable embodiment of a new-type asymmetrical CPC extraction cell 100 in longitudinal cross-section in partially cutaway perspective view and in outline top view. This embodiment of the extraction cell 100 is preferably produced using FDM (“fused deposition modelling”) 3D printing technology, although—as is known to a person skilled in the art—it may also be produced using lost core injection moulding.

[0042] Preferably e.g. peek, i.e. poly[phenyl-(4-phenylene doxy phenyl)ketone resin is used for the 3D printing, although other inert materials suitable for performing 3D printing may also be used, which is obvious for a person skilled in the art. The extraction cell 100 with its geometry to be detailed below is primarily suitable for carrying out CPC processes where the rate of flow of the mobile phase is a maximum of 250 ml/minute.

[0043] The extraction cell 100 has a cell wall 120 marking out the extraction chamber 150, which may be basically viewed as a three-dimensional shape with width “a”, thickness/depth “b” and height “c”, the dimensions of which preferably comply with the following relationships a≧b≧0.5a and 3a≧c≧2a. The three-dimensional shape is preferably a rectangular-based, inclined prism, specially a parallelepiped, at least the edges of which perpendicular to the a-c plane are rounded; in the case of a parallelepiped shape the geometric axis of the extraction cell 100 (not depicted in the drawing) when in its position in the CPC rotor (operation state) points essentially in the direction of the centre point of the CPC rotor (see the centre point O of the CPC rotor 400 constructed as an annular disc presented in FIG. 10), i.e. it coincides with the radius of the CPC rotor. At the same time, in its position in the CPC rotor (operation state), the geometric axis of the extraction cell 100 essentially in the shape of an inclined prism is at a determined angle to the radial line drawn from the centre point O of the CPC rotor to the geometric centre point of the extraction cell 100 (tilted cell); this angle is preferably selected so that the Coriolis force resulting from the rotation exerts the least possible effect on the flow occurring in the extraction cell 100 while in operation. Consequentially, from the point of view of the Coriolis force occurring in it during operation, the extraction cell 100 having such a tilted geometric axis can be treated as being optimised. In the light of the simulation tests performed aimed at determining the cell flow pattern, the angle of tilt of the extraction cell (depending on the length of the rotational radius and the planned speed of rotation of the CPC rotor) falls between 5° and 30°; with a rotational radius of 450 mm and a speed of rotation of 750 1/min. the angle of tilt of the extraction cell 100 is preferably between 15° and 18°, and even more preferably 16.5°.

[0044] The extraction chamber 150 of the extraction cell 100 has an inlet 115 and an outlet 140. The inlet 115 is structured so as to be divided into one or more inlet branches, where each inlet branch is connected to the extraction chamber through a circular inlet opening. Every one of these inlet openings is the same size, their diameters are preferably between 0.5 mm and 1.0 mm. Particularly, FIGS. 5 and 6 show an extraction cell 100 that has two inlet branches 115a, 115b, and, accordingly, two inlet openings 115a1 , 115b1. According to our investigations, the inlet 115 may be preferably divided into between two and ten inlet branches; the number of inlet branches is preferably between two and four, and is most preferably two. The inlet branches used open into the extraction chamber 150 perpendicularly. The centre points of the inlet openings belonging to the inlet branches are essentially located along a straight line, the straight line in question lies in the a-b plane and is essentially perpendicular to the width “a” of the extraction cell 100. The one or more inlet openings of the extraction cell 100 are essentially formed halfway along the width “a” of the cell, this position may be changed by a maximum of ±10% along the width “a” of the cell. According to the simulation tests, the branching of the inlet 115 has a positive effect on the flow pattern occurring in the cell during operation. From a closer aspect, the division of the inlet 115 into several inlet branches improves atomisation, in other words, it increases the size of the contact interface between the two phases present in the extraction cell 100, due to which the rate of material transport in the cell accelerates, which in practice, from the point of view of chromatography, means an increase in plate number.

[0045] The internal surfaces 125 of the extraction cell 100 according to the invention defined by the planes b-c are preferably not smooth but roughened. The roughening is preferably formed by steps or saw teeth created on the surfaces 125, the height of which is preferably between 0.1 mm and 0.4 mm. According to our investigations, the roughening of the internal surfaces 125 slightly increases the atomisation of the mobile phase and reduces the adhesion of the mobile phase to the surfaces 125.

[0046] The outlet 140 of the extraction cell 100 has one branch, i.e. it is not divided, also it has a circular cross-section. The size of the flow cross-section of the outlet 140 always exceeds the flow cross-section of an individual inlet branch. The simulation tests aimed at determining the flow pattern have clearly proven that an outlet 140 larger than the inlet 115 significantly reduces the dead volume occurring in the extraction cell 100.

[0047] From the point of view of reversibility of flow direction, the extraction cell 100 according to the invention is asymmetric, in other words, when performing CPC processes, the direction of flow in the cell cannot be reversed. The asymmetric construction is a result of the different cross-sections of the outlet 140 and the inlet branches as well as due to there being a collection pool 130 of a determined size established between the extraction chamber 150 and the outlet 140. As a result of this, the liquid phase leaving the extraction chamber 150 flows through this collection pool 130 before leaving through the outlet 140. In the light of the simulation tests, the collection pool 130 in question is preferably hemispherical, the radius of which hemisphere exceeds the diameter of the outlet 140, however, it is smaller than any of the “a”, “b” and “c” dimensions of the body containing the extraction cell 100. The diameter of the collection pool 130 is preferably equal to a half of the width “a” of the extraction cell 100.

[0048] Using the outlet 140 with the collection pool 130 significantly reduces the amount of back-mixed mobile phase, and also improves the settling efficiency, i.e. the mobile phase volume drops. This, from a chromatography point of view, reduces dead volume ratio and increases the stationary phase volume ratio. The solution in question also makes a greater flow rate possible, which increases the theoretical plate number and, with the increase in speed, increases the productivity of the CPC assembly.

[0049] On the basis of the simulation results (see Table 1), the technical solutions according to the invention, beside reducing dead volume, increase the size of the contact interface between the stationary and mobile phases, therefore two competing parameters are simultaneously improved.

[0050] As opposed to this, the currently available solutions were able to increase the size of the interface by increasing the flow rate of the mobile phase, which involved a significant increase in dead volume. On the basis of this, it is easy to see that in the case of the extraction cell 100 according to the invention, the peak resolution (R.sub.e), which characterises its separation ability, increases.

TABLE-US-00001 TABLE 1 Comparison of small volume extraction cells (planned for a 250 ml CPC column volume) Mobile Rotational Speed of Flow Specific phase radius rotation rate interface volume Cell (mm) (rpm) (ml/min.) (m.sup.−1) ratio Reference 105 1400 15 581 13.35% (Kromaton) Reference 70 200 15 885 17.24% (Armen) Own 550 750 15 1007 9.36% 3D FDM cell Own 550 750 20 1307 12.15% 3D FDM cell

[0051] FIG. 8 depicts an example of another preferable embodiment of a new type asymmetrical CPC extraction cell 200 according to the invention in longitudinal cross-section and in perspective outline view. This embodiment of the extraction cell 200 is preferably produced from peek material plates using CNC milling. The production work process is, to a certain extent, similar to the method presented in the US publication document No. US2010/0200488, where the halves of the cells are milled in individual plates, then following this, the whole cells are created by clamping together the two plates containing the two half-cells.

[0052] As compared to this solution, the main difference of the production process used by us is that the plates containing the milled cell halves are coated with a thin layer of a fluoropolymer (for example, by the heat-actuated continued polymerisation of a partially polymerised dispersion), then the coated plates are clamped together and subjected to heating, due to which the molecules of the polymer coating partially diffuse into one another and they adhere to one another forming appropriate insulation/sealing. In this way a single component is created in which the problem of leakage of the solutions between the layers does not appear. With respect to its geometry, the extraction cell 200 obtained in this way is very similar to the extraction cell 100 presented previously. The extraction cell 200 is primarily suitable for performing CPC processes where the flow rate of the mobile phase is a maximum of 1000 ml/min. The structure of the extraction cell 200 is very similar to the extraction cell 100 presented in FIG. 5. Accordingly, the cell wall 200 of the extraction cell 200 determines an extraction chamber 250, which extraction chamber 250 has an inlet 215 that opens into the extraction chamber 250 essentially perpendicularly, as well as an outlet 240 that serves to permit the liquid phase to leave the extraction chamber 250.

[0053] The inlet 215 may have one or more inlet branches, where all the inlet branches are each connected to the extraction chamber 250 via a circular inlet opening. All of the inlet openings in question are of the same size, their diameter is preferably between 0.5 mm and 1.0 mm. Particularly, FIG. 8 shows an extraction cell 200 that has one inlet branch and, accordingly, one inlet opening.

[0054] The outlet 240 of the extraction cell 200 is also single-branched, i.e. it is not divided and also has a circular cross-section. The flow cross-section of the outlet 240 exceeds the flow cross-section of the inlet. From the point of view of reversibility of flow direction, the extraction cell 200 according to the invention is also asymmetric, in other words, when performing CPC processes, the direction of flow in the cell cannot be reversed. The asymmetric construction is a result of the different cross-sections of the outlet 240 and the inlet 215, as well as due to there being a collection pool 230 of a determined size established between the extraction chamber 250 and the outlet 240. As a result of this, the liquid phase leaving the extraction chamber 250 flows through this collection pool 230 before leaving through the outlet 240. In the light of the simulation tests, the collection pool 230 in question, unlike the hemispherical collection pool 130 used in the case of extraction cell 100, preferably designates an inclined surface extending along the entire width of the bottom of the extraction chamber 250, which inclined surface is connected to the cell wall 240 without any distinct angles.

[0055] On the basis of the simulation tests performed (see Table 2) the extraction cell 200 according to the invention produced by CNC milling and by being fused together has significant advantages as compared to the currently available cells, as beside reducing dead volume, it increases the size of the contact interface between the stationary and mobile phases, therefore two competing parameters are simultaneously improved. Apart from this, it is able to operate at a much larger flow rate as compared to the volume of the cell, therefore, its productivity is much higher than the productivity of traditional cells.

TABLE-US-00002 TABLE 2 Comparison of medium volume cells (planned for a 1 litre CPC column volume) Rotational Speed of Flow Specific Mobile radius rotation rate interface phase Cell (mm) (rpm) (ml/min.) (m.sup.−1) volume Reference 105 1400 25 241 10.09% (Armen) Reference 105 1400 30 333 25.19% (Armen) Own 450 750 275 824 16.43% (No. 21) Own 450 750 200 638 13.5% (No. 22)

[0056] FIG. 9 depicts a module 300 of a modularly constructed CPC rotor according to the invention containing several CPC extraction cells 100, 200 connected to each other in series. The module 300 in question has channels 330 providing fluid links for the extraction cells 100, 200 formed on a carrier 310 or in the carrier 310 as well as a single liquid input 320 and a single liquid output 340.

[0057] FIG. 10 depicts a large (r>300 mm) disc CPC rotor 400 with an annular cross-section constructed using the CPC rotor modules 300 depicted in FIG. 9.

[0058] The modules 300 positioned on the sector segments 410 of the CPC rotor 400 are connected in series through tubes 430, where the liquid input of a selected module 300 is connected by tube 420 preferably to the liquid inlet located at the main axis of the CPC rotor 400, while the liquid outlet of the neighbouring module 300 is preferably connected by tube 420′ preferably to the liquid output located at the main axis of the CPC rotor 400.

[0059] In the case of the CPC rotor 400 according to the invention, the sum total of the extraction cells, channels and connections is produced from a single piece by plastic FDM 3D printing, or using similar technology. With this it is possible for the cell network to be made from fewer connected pieces as compared to the solutions according to the state of the art. This construction has the following advantages: [0060] The shape of the cells may be any chosen shape in the three dimensions, and in this way it may become possible to introduce the cell geometry discussed later on. [0061] The cross-section of the channels connecting the cells may be circular, instead of the previous rectangular cross-section, which reduces the pressure drop caused by the viscosity of the liquid, as well as the volume of the channels, which, to use a chromatography expression, counts as dead volume. [0062] It overcomes the fault of the liquid leaking in between the discs and the fluoropolymer seal between them due to the effect of the high pressure, which causes a transfer of contaminants between separation processes taking place at different times. [0063] In the past the discs and the seals had to be very precisely positioned with respect to one another, which greatly hindered assembly and servicing. Implementation using plastic FDM 3D printing technology is very similar to a CNC process (3 or more axis robot), however, it is not a subtractive but an additive process, due to which the amount of waste created is significantly less, therefore this production process is more environmentally friendly and economical.

[0064] Similarly to CNC procedures, devices suitable for working on large pieces are either very expensive or do not have the required degree of precision and speed.

[0065] It is easy to realise that the series of cells positioned in annular circular sector shapes may have an external housing, with the help of which the elements may be easily positioned into an annular disc.