Abstract:
The invention relates to air traps  13 , particularly for chromatography systems, chromatography systems using such air traps and methods of using such chromatography systems, in which the air trap comprises a liquid inlet pipe  33 , a liquid outlet pipe  35 , a substantially cylindrical reservoir  25  between the inlet and outlet pipes  33, 35 , and an air outlet opening, the air outlet opening being openable and closable by means of a valve, wherein the liquid inlet and outlet pipes  33, 35  connect to the reservoir  25  substantially tangentially to the reservoir wall  27 , the inlet pipe  33  at a distance above the outlet pipe  35 , arranged such that during use incoming liquid at a the maximum permitted flow rate travels a spiral path from the inlet pipe  33  to the outlet pipe  35 .

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a filing under 35 U.S.C. §371 and claims priority to international patent application number PCT/SE2006/000148 filed Feb. 2, 2006, published on Aug. 10, 2006, as WO 2006/083220, which claims priority to patent application number 0500321-5 filed in Sweden on Feb. 4, 2005; the disclosures of which are incorporated herein by reference in their entireties. 
     FIELD OF THE INVENTION 
     The present invention relates to air traps for removing gas bubbles from liquids, chromatographic systems provided with such air traps and methods for removing gas bubbles from chromatographic systems. 
     BACKGROUND OF THE INVENTION 
     The present invention is directed to air traps, and is particularly concerned with an arrangement for trapping and removing air or other gas bubbles from a liquid chromatography system. 
     In liquid chromatography a liquid sample is passed by a flowing stream of liquid solvent (the mobile phase) through a column packed with particulate matter (stationary phase). While passing through the column the various components in the sample separate from one another by adsorbing and desorbing from the stationary phase at different rates such that these individual components elute from the column at different times. The separated components then flow through a detector which responds to each component both qualitatively and quantitatively thereby providing information to the user about the separation achieved by the chromatography column. 
     The particulate matter in the chromatography column is generally referred to as the chromatography media and the resolution of a separation of the stream into individual components by the chromatography media is a primary measure determinant of the economic value of the chromatography. 
     Accordingly it is necessary to protect the chromatography media from conditions which will ruin the media including the presence of air and the presence of microbial contamination. 
     The presence of air (or other gas—in the following, in the interests of brevity, “air” and “gas” are used interchangeably to mean air and/or any other gas) in a chromatography column fills the pores of the chromatography media and blocks the liquid sample from getting to the active sites of the media. Additionally the presence of air disrupts the flow of the liquid sample which makes it impossible to achieve an even flow of the liquid sample through the column Additionally, dissolved air in the liquid may form bubbles under conditions of reduced pressure which are often present after the outlet of a chromatography column and these bubbles can interfere with the performance of detectors used to register the presence or absence of components of interest in the liquid leaving the column. 
     Microbial or bacterial contamination is a particular problem with low pressure chromatography because the liquid phase is aqueous and the gel media a carbohydrate. The presence of air can allow bacteria to grow which interferes with the ability of the media to produce a clean, pure product. 
     Accordingly it is highly desirable to prevent air from entering the column and to provide a air trap that not only excludes air from entering the column but also is of a sanitary design which inhibits the growth of bacteria within the chromatography system and, in particular the chromatography column Air traps are a known technique in liquid chromatography for protecting the chromatography column and more specifically the chromatography media. A typical air trap comprises a reservoir located at the down stream end of a system pump for delivering a liquid to a chromatography column The reservoir supplies the liquid to the chromatography column Any air whether from air entrapped in the liquid, or resulting from a slow leak or from a dry line condition would be trapped in the upper portion of the reservoir above the level of the liquid therein. 
     An example of such an air trap is known from U.S. Pat. No. 5,112,492. This teaches that the air trap may be positioned in a liquid chromatography system at the down stream end of the system pump and upstream of the chromatography column The air trap functions as a reservoir for receiving the entire volume output of the system pump and is provided with an inlet and an outlet (each provided with a valve) in the base of the reservoir and a top exhaust valve. The inlet and outlet valves are normally opened during operation while the exhaust valve is normally closed. A bypass valve may be located between the inlet and outlet valves to the air trap so that the air trap can be bypassed for certain operations such as sample loading of the liquid column The reservoir includes level detection devices at spaced elevations in the reservoir for the purpose of maintaining the liquid level above the outlet. 
     The operation of the air trap is controlled by a controller which receives inputs from the level sensors and sets the valves on the automated air trap according to the controller design. During normal operation, the air trap controls the level of the liquid between the lower and upper sensing levels and will shut down the operation in the event the liquid level can not be maintained between these two elevations. 
     During normal operation, the air trap will have inlet and outlet valves open. If the liquid level falls below the lower elevation, the system infers that air is being detected at the lower elevation, the outlet valve will close and the exhaust valve will open until the liquid level rises and it is detected at the upper elevation. If upper level detection of liquid does not occur within a preset time period, which will be dependent on the refill flow rate and on the air trap volume, then the system will shut down because a dry inlet line condition is inferred and the condition must be corrected before continuing operation. 
     In order to avoid bubbles in the incoming liquid being drawn into the outlet of the reservoir it is necessary to provide a distance between the inlet and outlets which is sufficiently long enough to allow incoming bubbles to rise to the top of the reservoir before the volume of liquid that they were present in leaves the reservoir. This requires a large reservoir volume which leads to an undesirable delay in the time it takes the sample being supplied to the chromatography column to reach the column. 
     BRIEF DESCRIPTION OF THE INVENTION 
     According to the present invention, at least some of the problems with the prior art are solved by means of an air trap system having the features present in the characterising part of claim  1 , a chromatography system in accordance with claim  5  and a method in accordance with claim  6 . 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  shows schematically a first embodiment of a chromatography system in accordance with the present invention. 
         FIG. 2  shows schematically a perspective view of a first embodiment of an air trap in accordance with the present invention. 
         FIG. 3  shows a lateral view of the air trap of  FIG. 2  and, in dashed lines, further embodiments of air traps in accordance with the present invention. 
         FIG. 4  shows a plan view of the air trap of  FIG. 2 . 
         FIG. 5  shows a perspective view of an embodiment of an air trap in accordance with the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An example of a chromatographic system in accordance with the present invention is shown schematically in  FIG. 1 . Features of such systems which are well-known in the art and which are not relevant to present invention have been omitted for clarity of illustration. The system  1  comprises a source  3  of liquid  5  which is to be passed through at least one chromatography column  7 . The liquid is pumped by a pump  9  though a conduit  11  to an air trap 13  in accordance with the present invention before continuing through conduit  15  to the inlet  17  of chromatography column  7 . The liquid passes through media  19  in the column and exits the column via the outlet  21  of the column  7  into conduit  23 . Conduit  23  leads the liquid to a further destination which could be, for example, a further column, a storage tank, a fraction collector or a waste drain. 
       FIG. 2  shows a perspective view of one embodiment of an air trap  13  in accordance with the present invention.  FIGS. 3 and 4  show respectively a lateral and a plan view of the same air trap  13 . Air trap  13  comprises an air tight cylindrical reservoir  25  with a cylindrical wall  27  of length L and diameter Ø1, capped at one end by a first end surface  29  and at the other end by second end surface  31 . In this example the reservoir  25  is shown orientated with its longitudinal axis substantially vertical and end surface  29  on top. Optionally, reservoir  25  may be made of a transparent material or be provided with transparent windows to allow visual inspection of the interior of the reservoir  25 . 
     Reservoir  25  is provided with an inlet pipe  33  which is attached to and penetrates the wall  27  with its closest approach to first end surface  29  being at a distance D 1  from the first end surface  29 . Inlet pipe  33  is arranged to penetrate wall  27  at a tangent to wall  27 . Reservoir  25  is further provided with an outlet pipe  35  which is attached to, and penetrates the wall  27 , with its closest approach to first end surface  29  being at a distance D 2  which is greater than D 1  from the first end surface  29 . Outlet pipe  35  is arranged to penetrate wall  27  at a tangent to wall  27  and may optionally, to facilitate maintenance access to the inlet and outlet pipes  33 ,  35 , be arranged so that when looking down from the first end surface  29  towards second end surface  31 , it appears that inlet pipe  33  is substantially aligned with outlet pipe  35 . Upper end surface  29  is provided with an air outlet opening  37  and exhaust valve  38  which is able to be manually and/or automatically operated to release gas trapped inside the air trap. 
     A level sensor is arranged to detect when the level of liquid in the reservoir  25  falls to a level D 3  where D 3  is less than D 1 . If the occurs then exhaust valve  37  may be operated to release gas from the reservoir and allow the level of liquid to rise in order to avoid disturbances in the flow path. This arrangement ensures that there is always a minimum depth of liquid in the reservoir  25  during use. Optionally, and preferably, reservoir  25  is provided with a central protuberance  39  which has a diameter Ø2 which is less than Ø1. Central protuberance  39  may extend from the second end surface  31  to the first end surface  29  as shown in  FIG. 2 , or, in another embodiment of the present invention (see  FIG. 5 ), from the second end surface to a distance D 4  which is less than the full height of the reservoir. Central protuberance  39  serves to limit the lowest attainable velocity in the centre of the reservoir and reduces the tendency for stagnant volumes to form in the reservoir  25 . At the same time, the volume liquid contained in the reservoir  25  is reduced. 
     In use, the pumped liquid enters reservoir  25  through inlet pipe  33  at the upper side of the reservoir  25 , somewhat below the liquid surface in the reservoir  25 . The path that incoming liquid takes between the inlet and outlet pipes  33 ,  35  depends on its flow rate. At a low flow rate which depends, amongst others, on the viscosity of the liquid, the positioning of the inlet and outlet pipes and the distance between them, the incoming fluid takes the shortest path between the inlet and outlet pipes and is subjected to little or no centrifugal force. In this case bubbles leave the liquid by rising under the influence of gravity. As the flow rate of the incoming liquid increases its tangential velocity component is too high for it to take the shortest path between the inlet and outlet pipes. Instead, the liquid is forced to circulate around the curved wall of the reservoir  25 , and is subject to centrifugal forces. The liquid is forced by its tangential velocity component, the shape of the reservoir  25  and the positioning of the inlet and outlet pipes  33 ,  35  to follow a spiral path downwards and finally out of the reservoir  25  via outlet pipe  35 . 
     Since the centrifugal forces acts more strongly on the liquid (which has a higher density than air), air is pressed toward the centre of the reservoir  25  (where the velocity is lower) while at the same time it floats upwards due to the effect of the force of gravity. As the outlet is on the circumference of the reservoir and bat a lower level than the inlet the combined influence of gravitational and centrifugal forces provide a more efficient de-airing and enables an air trap according to the present invention to have a lower liquid volume that prior art air traps of similar de-airing capacity used in chromatography systems. 
     Optionally, as shown in  FIGS. 2-4 , vanes  41  may be provided inside the reservoir  25  to guide the liquid in a spiral path from the inlet pipe  33  to the outlet pipe  35 . 
     As shown by dashed lines in  FIG. 3 , in another embodiment of the present invention the inlet pipe  33  is arranged to be not parallel with the end surfaces of the reservoir, instead it is inclined towards the second end surface, so that incoming liquid is inputted with a flow vector in a direction towards the second end surface  31 . 
       FIG. 5  shows a perspective view of an embodiment of an air trap in accordance with the present invention in which the reservoir has a transparent wall and the central protuberance. 
     An air trap in accordance with the present invention has the advantage that the separation of bubbles from liquid increases as the flow velocity through the air trap increases, in other words the faster the flow, the better the separation. This is in contrast to prior art air traps used in chromatography systems which have had an inverse relationship between flow velocity and separation. Additionally, even at liquid flows rates too low to cause the incoming liquid to take a spiral path from the inlet to the outlet of the reservoir an adequate remove of air bubbles from the incoming liquid can be achieved. This is because with such flow rates the liquid takes a relatively long time to travel from the upper inlet pipe to the lower outlet pipe and this allows bubbles in the liquid enough time to rise to the top of the reservoir. 
     Preferably an air trap in accordance with the present invention is designed such that when it is operated at its maximum permitted flow rate the centrifugal force exerted on the fluid flowing along a spiral path through the reservoir is at least 1 G. More preferably the centrifugal force exerted on the fluid when flowing along a spiral path through the reservoir at the maximum permitted flow rate is at least 2 G. Even more preferably the centrifugal force exerted on the fluid when flowing along a spiral path through the reservoir at the maximum permitted flow rate is at least 3 G. The dimensions of an air trap needed to give the abovementioned forces can be calculated from the following: 
     The centrifugal acceleration (a cent ) that drives the separation depends on the tangential velocity component (v t ) and the radius of the air trap (R trap ). Since v t  is proportional to the flow rate at the inlet to the air trap, an expression for the a cent  is obtained: 
               a   cent     =         v   t   2       R   trap       ∝         (     Q     A   inlet       )     2     /     R   trap               
where
 
Q is the volume flow through the air trap, and
 
A inlet  is the area of the cross sectional area of the air trap inlet.
 
     In order to provide a centrifugal acceleration that gives a better air separating effect than that obtained by the gravitational acceleration (G), i.e. the separating centrifugal effect dominates the gravitational separating effect, an important design criteria is to determine a minimum value for the ratio between a cent  and G, for example: 
                 a   centMAX     G     ∝         (       Q   MAX       A   inlet       )     2     /     (     gR   trap     )       ≥   2         
ie., based on a maximum permitted flow rate (Q MAX ) through the trap, and the assumption that the centrifugal acceleration (a cent ) should be at least equal to the gravitational acceleration (G), the radius of the air trap (R trap ) can be determined for a specific inlet area. Typically the inlet area is the same as the general conduit diameter of the separation system in which the air trap is installed but this is not obligatory.
 
     The skilled person will recognise that other orientations of the air trap in accordance with the present invention are also possible, for example with the longitudinal axis of the reservoir inclined at an angle, provided arrangements are made to ensure correct functioning of the exhaust valve, level sensing and, preferably, that drainage of all to liquid from the trap can be readily achieved. 
     The above examples illustrate specific aspects of the present invention and are not intended to limit the scope thereof in any respect and should not be so construed. Those skilled in the art having the benefit of the teachings of the present invention as set forth above, can effect numerous modifications thereto. These modifications are to be construed as being encompassed within the scope of the present invention as set forth in the appended claims.