EP2646686A1

EP2646686A1 - A chromatography pump

Info

Publication number: EP2646686A1
Application number: EP11790755.0A
Authority: EP
Inventors: Owe Salven; Bjorn Olovsson; Mats Lundkvist; Jan Kranse
Original assignee: GE Healthcare Bio Sciences AB
Current assignee: Cytiva Sweden AB
Priority date: 2010-11-30
Filing date: 2011-11-24
Publication date: 2013-10-09
Also published as: WO2012072494A1; JP2014505194A; US20130259723A1; CA2819114A1; CN103221688A

Abstract

The invention relates to a chromatography pump, comprising a cylinder (202, 402) in which a piston (204, 404) is arranged for a reciprocating movement; a front element (208) provided with a cylinder head area (210) which together with the cylinder (202, 402) and the piston (204, 404) defines a cylinder space (212); an inlet valve (214) and an outlet valve (216) arranged in the front element (208); an inlet channel (218) arranged in the front element (208) between the inlet valve (214) and the cylinder head area (210); an outlet channel (220) arranged in the front element (208) between the cylinder head area (210) and the outlet valve (216). The inlet channel (218) and outlet channel (220) extend in a substantially straight direction, so that air bubbles (234) are prevented from being trapped within the inlet and outlet channels (218, 220).

Description

A chromatography pump

TECHNICAL FIELD The present invention relates to a chromatography pump according to the preamble of claim 1.

Chromatography is a chemical process for identifying and quantifying compositions held in a sample and also for purification and extraction of compositions. In the process, compositions in a solution are separated from each other as the solution moves through a stationary material held in a column.

The solution is pumped under high pressure through the stationary material in the column by one or several chromatography pumps. BACKGROUND ART

In chromatography and especially in liquid chromatography often only very small samples of the material to be analyzed or purified are available. The process during mixing gradients of two different liquids is also sensitive for rapid changes in the flow and pressure of solution as it moves through the stationary material in the column. For this reason the chromatography pump system has to be very accurate in order to achieve a minimum of fluctuation in flow output and pressure from the chromatography pump.

In the preparation for the chromatography process air held in the chromatography pump has to be removed. Also, air held in the sample has to be removed. Therefore, chromatography pump systems often are provided with a purging arrangement which removes the air held in the chromatography pump in the beginning of the process. The purging arrangement generates a vacuum at the outlet valve of the pump, so that air held within the pump is sucked out from the pump and the solution or sample simultaneously is sucked into the pump.

However, to some extent air bubbles tend to be trapped within the chromatography pump cylinder even if the purging arrangement has removed the major volume of air held in the chromatography pump. The air bubbles trapped within the chromatography pump reduces the performance of the chromatography pump, so that the pressure and flow of the solution will fluctuate. This will influence on the overall chromatography mixing process, so that less accurate results will be achieved. In a chromatography pump available in the prior art, which will be described in more detail below together with fig. 1 , air bubbles tend to be trapped in the inlet and outlet channels of the pump, and also in the cylinder. The air bubbles are trapped at stagnant zones i.e. at edges and corners formed in the known pump.

SUMMARY OF THE INVENTION

The object of the invention is to achieve a chromatography pump with automatic purging, which eliminates manual means for the purging operation.

Another object of the invention is to achieve a chromatography pump which facilitates air bubbles to be transported through the pump.

A further object of the invention is to achieve a chromatography pump in which air bubbles are prevented to be trapped.

A further object of the invention is to achieve a minimum of fluctuation in flow output and pressure of a chromatography pump. These objects are achieved by a chromatography pump according to claim 1.

Since the inlet channel and outlet channel extend in a substantially straight direction there are no edges and corners where air bubbles can be trapped within the channels. Instead the air bubbles will pass through the cannels without influencing the performance of the chromatog- raphy pump. Thus, a chromatography pump with high performance is achieved.

According to an aspect of the invention an outlet of the inlet channel arranged in the cylinder head area has a substantially elliptic configuration. This configuration facilitates air bubbles to be transported out of the inlet channel and further to the outlet channel.

According to a further aspect of the invention a cavity is arranged in the cylinder head area and an inlet of the outlet channel is arranged in the cavity. Thereby, air bubbles coming from the inlet channel and air bubbles in the cylinder will easily be transported out to the outlet channel. According to a further aspect of the invention the cavity has a form substantially corresponding to an arch. This configuration facilitates the transport of air bubbles out to the outlet channel. According to a further aspect of the invention the front element is made of PEEK material, titanium or hastelloy. Thereby, a high strength of the front element is achieved. Also, the surface properties of these materials can be adapted to prevent air bubbles to be trapped and tied on the surfaces in the channels and in the cylinder.

According to a further aspect of the invention the surface roughness (Ra) of the walls of the inlet and outlet channels and of the wall of the cylinder head area are between 0,2 - 2,0, preferably between 1 ,0 - 2,0. This will prevent air bubbles to be tied to the surface of the inlet and outlet channels and of the wall of the cylinder head area.

According to a further aspect of the invention the inlet and outlet valves are check valves provided with seated balls in which a weight arranged on the ball urges the ball against the seat. Thereby, air bubbles are prevented from being trapped between the ball and the seat due to the force from the ball on the seat. Also, between the ball and the inner wall of the valve capil- lary forces caused by air bubbles make the ball get stuck to the inner wall. This is prevented by the weight arranged on the ball.

According to a further aspect of the invention the cylinder head area has a normal which substantially coincides with the axis of the piston. Thus, a compact design of the cylinder space is achieved. Because the inlet and outlet channels are connected to the cylinder head area and that the normal of the cylinder head area substantially coincides with the axis of the piston air bubbles in the cylinder will easily be transported out to the outlet channel.

BRIEF DESCRIPTION OF THE DRAWINGS

Further aspects, advantages and features of the invention can be derived from the following detailed description of exemplary embodiments of the invention, with reference to the drawings.

Fig. 1 shows a diagrammatic cross section view of a prior art chromatography pump,

Fig. 2 shows a cross section view of a preferred embodiment of a chromatography pump according to the invention,

Fig. 3 shows a front view of the preferred embodiment of the chromatography pump according to the invention, Fig. 4 shows a cross section view of a second embodiment of a chromatography pump according to the invention,

Fig. 5 shows a cross section view of a third embodiment of a chromatography pump according to the invention, and

Fig. 6 shows an enlarged cross section view of a forth embodiment of a piston for a chromatography pump according to the invention. DETAILED DESCRIPTION

Fig. 1 shows a diagrammatic cross section view of a prior art chromatography pump 101 , which comprises a cylinder 102 in which a piston 104 is arranged for a reciprocating movement. The reciprocating movement of the piston 104 is generated by a driving means 106, such as an electric motor. A front element 108 is provided with a cylinder head area 110 which together with the cylinder 102 and the piston 104 defines a cylinder space 112. An inlet valve 114 and an outlet valve 116 in form of check valves are arranged in the front element 108. An inlet channel 118 is arranged in the front element 108 between the inlet valve 114 and the cylinder head area 110, and an outlet channel 120 is arranged in the front element 108 between the cylinder head area 110 and the outlet valve 116. When the piston 104 moves in the left direction in fig. 1 a liquid 122 held in a schematically disclosed container 124 is sucked into the cylinder space 112 through the inlet valve 114 and the inlet channel 118 due to vacuum generated in the cylinder space 112 by the piston 104. When the vacuum generated sucks the liquid 122 through the inlet valve 114 a ball 126 within the valve 114 lifts from a seat 128 by the flow of the liquid and open a passage for the liquid 122 between the ball 126 and the seat 128. At the same time liquid 122 is prevented from entering the outlet valve 116 because the ball 126 seals against the seat 128.

When the piston 104 thereafter changes direction and moves in the right direction in fig. 1 the liquid 122 is pressed out of the cylinder space 112 through the outlet channel 120 and out of the outlet valve 116 due to the pressure generated in the cylinder space 112 by the piston 104. From the outlet valve 116 the liquid flows to a schematically disclosed column 130 in which a stationary material 132 is held. From the column 130 the liquid which has passed the column 130 is led to a waste container 131 or a fraction collector. When the pressure press the liquid 122 through the outlet valve 116 the ball 126 within the valve 116 lifts from the seat 128 by the flow of the liquid 122 and open a passage for the liquid 122 between the ball 126 and the seat 128. At the same time liquid 122 is prevented from escaping the inlet valve 114 because the ball 126 seals against the seat 128.

However, air bubbles 134 tend to be trapped within the known chromatography pump 101 dis- closed in fig. 1 , especially in the inlet and outlet channels 1 18, 120 of the pump 101 , and also in the cylinder space 112. One reason why the air bubbles 134 are trapped in the inlet and outlet channels 118, 120 is that the channels1 18, 120 are provided with stagnant zones, such as edges and corners 136. Another reason is that the surface roughness of the wall surface of the channels are too smooth, which facilitates air bubbles 134 to be tied to the surfaces. Similar drawbacks can be found in the cylinder space 112 at the cylinder head area 110. Air bubbles 134 can also be trapped between the ball 126 and the seat 128 in the inlet and outlet valves 1 14, 1 16. The trapped air bubbles 134 can also prevent the ball 126 from returning back to the seat 128 due to capillary forces. As mentioned above the air bubbles 134 trapped within the chromatography pump 101 reduces the performance of the pump 101 , so that the pressure and flow of the liquid 122 will fluctuate. This will influence on the overall chromatography process, so that less accurate results will be achieved. Fig. 2 shows a cross section view of a preferred embodiment of a chromatography pump 201 according to the invention. The chromatography pump 201 comprises a cylinder 202 in which a piston 204 is arranged for a reciprocating movement along an axis 248. A seal means 205 is arranged on the piston 204, so that leakage between the piston 204 and the cylinder 202 is minimized. The reciprocating movement of the piston 204 is generated by a driving means 206, such as an electric motor. A front element 208 is provided with a cylinder head area 210 which together with the cylinder 202 and the piston 204 defines a cylinder space 212. An inlet valve 214 and an outlet valve 216 in form of check valves are arranged in the front element 208. An inlet channel 218 is arranged in the front element 208 between the inlet valve 214 and the cylinder head area 210, and an outlet channel 220 is arranged in the front element 208 between the cylinder head area 210 and the outlet valve 216. When the piston 204 moves in the left direction in fig. 2 a liquid 222 held in a schematically disclosed container 224 is sucked into the cylinder space 212 through the inlet valve 214 and the inlet channel 218 due to vacuum generated in the cylinder space 212 by the piston 204. When the vacuum generated sucks the liquid 222 through the inlet valve 214 a ball 226 within the valve 214 lifts from a seat 228 by the flow of the liquid 222 and open a passage for the liquid 222 between the ball 226 and the seat 228. At the same time liquid 222 is prevented from entering the outlet valve 216 because the ball 226 seals against the seat 228. At the beginning of the pumping process the cylinder 202, channels 218, 220 and valves 214, 216 are filled with air. Therefore, during a certain period of time the air will be pumped out of the cylinder 202, channels 218, 220 and valves 214, 216 by the reciprocating movement of the piston 204. Thus, the chromatography pump 201 according to the invention is self purging.

When the piston 204 thereafter changes direction and moves in the right direction in fig. 2 the liquid 222 is pressed out of the cylinder space 212 through the outlet channel 220 and out of the outlet valve 216 due to the pressure generated in the cylinder space 212 by the piston 204. From the outlet valve 216 the liquid 222 flows to schematically disclosed column 230 in which a stationary material 232 is held. From the column 230 the liquid which has passed the column 230 is led to a waste container 231 or a fraction collector. When the pressure press the liquid 222 through the outlet valve 216 the ball 226 within the valve 216 lifts from the seat 228 by the flow of the liquid 222 and open a passage for the liquid 222 between the ball 226 and the seat 228. At the same time liquid 222 is prevented from escaping the inlet valve 214 because the ball 226 seals against the seat 228. An example of pressure and piston displacement of the chromatography pump 201 according to the invention is 200 bar and 125 μΙ. The flow generated by the pump is in the range 0 - 60 ml/minute.

The inlet and outlet channels 218, 220 in fig. 2 extend in a substantially straight direction with- out or with as few sharp edges or corners as possible, so that air bubbles 234 are prevented from being trapped within the channels 218, 220. The channels 218, 220 are not provided with stagnant zones, such as edges and corners, and therefore air bubbles 234 will not be trapped within the channels. Instead the air bubbles 234 will pass through the cannels 218, 220 without influencing the performance of the chromatography pump 201. In addition, the outlet channels extend obliquely to axis 248, as can be seen in the Figures. In other words, the outlet channels 218 and 220, provide a substantially straight line connection between the cylinder head area 210 and their respective valves 214 and 216, and the straight lines are slanted relative to the axis 248 of the piston 204, and have divergent paths. Thus, with this arrangement of a chromatography pump 201 , high performance is achieved. The configuration of the channels 218 and 220 provides improved flow, and also facilitates the cleaning of the pump 201. This is especially important when different liquids are used in the pump 201. When changing liquids to be pumped it was common in the prior art that air bubbles were trapped within the pump. In the pump 201 according to the invention air bubbles 234 are unlikely to be trapped and the pump 201 will be purged automatically.

The surface roughness (Ra) of the walls 236 of the inlet and outlet channels 218, 220 and of the wall 238 of the cylinder head area 210 are between 0,2 - 2,0, preferably between 1 ,0 - 2,0. This will prevent air bubbles 234 to be tied to the wall 236 of the inlet and outlet channels 218, 220 and of the wall 238 of the cylinder head area 210. The surface roughness can be achieved by special machining techniques. The front element 208 is preferably made of PEEK material, titanium or hastelloy. Other materials are also possible. PEEK and hastelloy are registered trademarks. Thereby, a high strength of the front element 208 is achieved. Also, the surface properties of these materials can be adapted to the above-mentioned surface roughness values. The liquid 222 must be pumped under high pressure through the stationary material 232 in the column 230. Therefore, the materials used in the front element 208 must have high strength properties.

Fig. 3 shows a front view of the preferred embodiment of the chromatography pump 201 according to the invention. A cavity 242 is arranged in the cylinder head area 210 and an outlet 240 of the inlet channel 218 is arranged in the bottom part of the cavity 242. Also, an inlet 244 of the outlet channel 220 is arranged in the cavity 242. Thereby, air bubbles 234 coming from the inlet channel 218 and air bubbles 234 in the cylinder space 212 will easily be transported out to the outlet channel 220. Preferably, the cavity 242 has a form substantially corresponding to an arch and the inlet 244 of the outlet channel 220 has conical form. This configuration facilitates the transport of air bubbles 234 out to the outlet channel 220. However, it is possible to arrange the outlet 240 of the inlet channel 218 outside the cavity 242.

The cylinder head area 210 has a normal 246 which substantially coincides with the axis 248 of the piston 204. Thus, a compact design of the cylinder space 212 is achieved. Since the inlet and outlet channels 218, 220 are connected to the cylinder head area 210 and that the normal 246 of the cylinder head area 210 substantially coincides with the axis 248 of the piston 204 air bubbles 234 in the cylinder 202 will easily be transported out to the outlet channel 220.

Fig. 4 shows a cross section view of a second embodiment of a chromatography pump 301 according to the invention. Similar components as disclosed in fig. 2 will have same reference numbers. The inlet and outlet valves 214, 216 are provided with seated balls 226 in which weights 303 are arranged on the balls 226 that urges the balls 226 against the seat 228. Thereby, air bubbles 234 are prevented from being trapped between the ball 226 and the seat 228 due to the force from the ball 226 on the seat 228. Also, the ball 226 is prevented from being stuck to the inner wall of the valves 214, 216 due to capillary forces. The weights 303 are influenced by gravity forces and therefore the pump 301 according to this second embodiment has to be mounted in such a direction that the weights 303 rests on the balls 226 in the valves 214, 216. Instead or in combination with the weight 303 it is also possible to arrange a spring (not disclosed) in the valves 214, 216, which urges the ball 226 against the seat 228. Fig . 5 shows a cross section view of a third embodiment of a chromatography pump 301 according to the invention. Similar components as disclosed in fig. 3 will have same reference numbers. According to this embodiment the outlet channel 220 and the inlet and outlet valves 214, 216 extend in a substantially coincident direction, so that the pump 301 may be mounted with outlet channel 220 in a substantially vertical direction in relation to a horizontal plane 308. As a result air bubbles 234 within the pump 301 will easy leave the outlet channel 220, because of the gravitation influencing on the air bubbles 234 in the liquid. Fig. 6 shows an enlarged cross section view of a forth embodiment of a piston 404 for a chromatography pump 401 according to the invention. The piston 404 is provided with a circumferential seal 405 which in a direction radial outwardly is spring loaded by a circumferential leaf spring 407, so that a tight seal between the cylinder 402 and the piston 404 is achieved. A tap 409, preferably made of titanium is arranged on the end part 41 1 of the piston 402. The tap 409 is attached to the piston 404 and fixates the seal 405 on the end part 41 1 of the piston 404.

The chromatography pump 201 , 301 , 401 according to the present invention is primary designed for pumping liquid 222. However, other fluids may also be pumped by the chromatography pump 201 , 301 , 401 according to the invention.

Claims

1. A chromatography pump, comprising a cylinder (202, 402) in which a piston (204, 404) is arranged for a reciprocating movement along an axis (248); a front element (208) provided with a cylinder head area (210) which together with the cylinder (202, 402) and the piston (204, 404) defines a cylinder space (212); an inlet valve (214) and an outlet valve (216) arranged in the front element (208); an inlet channel (218) arranged in the front element (208) between the inlet valve (214) and the cylinder head area (210); an outlet channel (220) arranged in the front element (208) between the cylinder head area (210) and the outlet valve (216), characterized in that the inlet channel (218) and outlet channel (220) extend in a substantially straight direction, and in that the inlet channel (218) and outlet channel (220) each extend obliquely to the axis (248).

2. A pump according to claim 1 , characterized in that a cavity (242) is arranged adjacent the the cylinder space (212)and in that an inlet (244) of the outlet channel (220) is arranged in the cavity (242).

3. A pump according to claim 2, characterized in that an outlet (240) of the inlet channel (218) is arranged in the cavity (242).

4. A pump according to claim 2 or 3, characterized in that the cavity (242) has a form substantially corresponding to an arch, so that air bubbles (234) are prevented from being trapped within the cavity (242).

5. A pump according to any of the preceding claims, characterized in that the front element (208) is made of PEEK material, titanium or hastelloy.

6. A pump according to any of the preceding claims, characterized in that the surface roughness (Ra) of the walls (236) of the inlet and outlet channels (218, 220) is between 0,2 - 2,0, preferably between 1 ,0 - 2,0.

7. A pump according to any of the preceding claims, characterized in that the surface roughness (Ra) of the wall (238) of the cylinder head area (210) is between 0,2 - 2,0, preferably between 1 ,0 - 2,0.

8. A pump according to any of the preceding claims, characterized in that the inlet and outlet valves (214, 216) are check valves provided with seated balls (226) in which a weight (303) arranged on the ball (226) urges the ball (226) against the seat (228).

9. A pump according to any of the preceding claims, characterized in that the cylinder head area (210) has a normal (246) which substantially coincides with the axis (248) of the piston (204).

10. A pump according to any of the preceding claims, characterized in that the chromatog- raphy pump (201 , 301 , 401) is designed for pumping liquid (222).

1 1. A pump according to any of the preceding claims, characterized in that a circumferential seal (405) is arranged on the piston (404), and a circumferential leaf spring (407) is arranged to apply an outwardly directed radial load on the seal (405).

12. A pump according to claim 11 , characterized in that a tap (409) is arranged on an end part (41 1) of the piston (404), which tap (409) is attached to the piston (404) and fixates the seal (405) on the end part (41 1) of the piston (404).

13. A pump according to any of the preceding claims, characterized in that the outlet channel (220) and the inlet and outlet valves (214, 216) extend in a substantially coincident direction, so that the pump may be mounted with outlet channel (220) in a substantially vertical direction in relation to a horizontal plane (308).