Patent Publication Number: US-10788468-B2

Title: Clamp for chromatography columns

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of PCT/US2018/067974 filed on Dec. 28, 2018, which claims priority to U.S. application Ser. No. 15/858,871 filed on Dec. 29, 2017, the disclosures of which are incorporated by reference herein in their entireties. 
    
    
     TECHNICAL FIELD 
     This presentation relates to a method and corresponding apparatus for coupling in series two chromatography columns. 
     BACKGROUND 
     Chromatography techniques such as liquid chromatography, gas chromatography, low pressure chromatography, medium pressure chromatography, high-performance liquid chromatography (HPLC), ultra-high performance chromatography (UHPLC), etc. can be used, for example, in an analytical role or in a preparative role to separate, identify, and quantify the components of a mixture. Such techniques essentially pass a fluid (“mobile phase”) containing a sample mixture through a column containing a separation medium (“stationary phase.”) The stationary phase and mobile phase can be chosen such that components in the sample have different affinity for the stationary and mobile phase, causing different flow rates for the different components and leading to the separation of the components as they flow through the column. The stationary phase can be a granular material comprising, for example, a ceramic or a polymeric material, selected for the particular separation being performed. 
     It is desirable for a chromatography system to be arranged to quickly, easily and reliably couple two chromatography columns in a chromatography system. 
     SUMMARY 
     Embodiments of this presentation provide for a clamp for chromatography columns, that has a first seal, for example a non-movable seal, with a first opening a movable seal with a second opening and a movable coupler. The movable coupler has first and second coupler seals with communicating third and fourth openings. The clamp is arranged for pressing a first chromatography column between the first seal and the first coupler seal and for pressing a second chromatography column between the movable seal and the second coupler seal, such that the first opening fluidly communicates with the second opening through the first chromatography column, the third and fourth openings and the second chromatography column. 
     In a first aspect disclosed herein a clamp for chromatography columns is provided, the clamp having a first seal with a first opening, a movable seal with a second opening and a movable coupler; the movable coupler having first and second coupler seals with communicating third and fourth openings; the clamp being configured for pressing a first chromatography column between the first seal and the first coupler seal and pressing a second chromatography column between the movable seal and the second coupler seal, such that the first opening fluidly communicates with the second opening through the first chromatography column, the third and fourth openings and the second chromatography column. 
     In a second aspect disclosed herein a chromatography column clamp is provided, the chromatography claim is arranged: to receive two chromatography columns between a first compression seal and a movable compression seal; and to press said two chromatography columns on opposite sides of a compression seal coupler by urging the movable compression seal toward the first compression seal. 
     In a third aspect disclosed herein, a method of clamping two chromatography columns in series is provided, the method comprising: receiving two chromatography columns between a first compression seal and a movable compression seal; and pressing said two chromatography columns on opposite sides of a compression seal coupler by urging the movable compression seal toward the first compression seal. 
     These and other features and advantages will become further apparent from the detailed description and accompanying figures that follow. In the figures and description, numerals indicate the various features; like numerals referring to like features throughout both the drawings and the description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a cross-section view of a clamp for chromatography columns according to an embodiment of this presentation, in a work position. 
         FIG. 2  is a cross-section view of a clamp for chromatography columns according to an embodiment of this presentation, in a rest position. 
         FIG. 3  is a top view of a clamp for chromatography columns according to an embodiment of this presentation, in a rest position. 
         FIG. 4  is an elevation view of a clamp for chromatography columns according to an embodiment of this presentation, in a rest position. 
         FIG. 5  is a cut-away view of the clamp for chromatography columns shown in  FIG. 4 . 
         FIG. 6  is a cut-away view of the clamp for chromatography columns shown in  FIG. 4 , with the first and second chromatography columns removed, and showing installation. 
     
    
    
     DETAILED DESCRIPTION 
     In the following description, numerous specific details are set forth to clearly describe various specific embodiments disclosed herein. One skilled in the art, however, will understand that the present disclosure may be practiced without all of the specific details discussed below. In other instances, well known features have not been described so as not to obscure the understanding of the disclosure. In the present disclosure, the same references indicate the same elements in the various figures. 
     Chromatography can be used for separating components for manufacturing purpose, as well as for analysis purpose (detecting if specific products are present in a solution). 
     Chromatography can be categorized based on the pressure used to pass the mobile phase through the stationary phase. For example, HPLC utilizes a higher pressure than medium pressure chromatography, which utilizes a higher pressure than low pressure chromatography with utilizes a higher pressure than flash chromatography. In some forms of chromatography, gravity or a liquid column can be used as the pressure source. 
     A chromatography system can include a detector arranged to generate a signal related to the amount of sample component emerging from the column, thus allowing for quantification of the sample components. HPLC instruments can have a column heater that allows for adjusting the temperature at which the separation is performed. 
     A chromatography system can fluidly couple a first chromatography column, such as one that serves as a prefilter or fluid conditioner, upstream of a second chromatography column which contains a stationary phase, for example to filter out large particles from the sample that would otherwise impair the flow of the sample through the stationary phase, or to otherwise condition the mobile phase or the sample. In some embodiments, a chromatography column can have threaded end connections. However, due to the possibility of over-tightening or under-tightening, leaks and/or alignment issues can arise during operation. Further, properly tightening a threaded connection can require special tools and additional time to accomplish, both adding to the burden put on the user. 
     An embodiment of this presentation relates to a clamp arranged to fluidly couple two chromatography columns, such as by pressing two chromatography columns on opposite sides of a compression seal coupler. The two chromatography columns can be pressed between a first (for example a non-moving) compression seal and a movable, pressure applying, compression seal. As used herein, “chromatography column” can be used to refer to a column that contains the stationary phase that can provide separation of sample components and can be used to refer to other chromatography system components such as a “pre-column”, “guard column”, filter, pre-filter, post-filter as well as component(s) that react with one or more components of the mobile phase or sample, such as to remove, neutralize, modify or change the detectability of a component. Frequently, these other chromatography system components can be arranged in series with the chromatography column that contains the stationary phase. In some embodiments, two or more chromatography columns that contain stationary phase (either the same or different from one another) are also contemplated. 
       FIG. 1  is a cross-section view of a clamp for chromatography columns  10  according to an embodiment of this presentation, the clamp  10  having on one side a first, for example non-movable, seal  12  with a first opening  14 ; and on another side a movable seal  16  with a second opening  18 . Between the two sides, clamp  10  comprises a movable coupler  19  that comprises a first coupler seal  20  with a third opening  24  and a second coupler seal  22  with a fourth opening  26 . The third and fourth openings  24 ,  26  can fluidly communicate via a lumen  27 . By “non-movable” in reference to a seal, means that no specific mechanism is provided to actively change the position of the first seal  12  in operation of the clamp  10 . As detailed herein, in some embodiments the position of the first seal  12  can be tuned/calibrated to account for a change of length of the chromatography columns or to vary the compressive force. As detailed herein, the position of the first seal  12  as a non-moving seal can in some embodiments vary its position in response to the pressure exerted by movable seal  16  through the chromatography columns  28 ,  30  and the mobile coupler  19 . 
     According to an embodiment of this presentation, and as detailed hereafter, clamp  10  can be arranged for pressing a first chromatography column  28  (for example a filter column, a pre-column, a guard column or a stationary phase column) between the first seal  12  and the first coupler seal  20  and for pressing a second chromatography column  30  (for example a column containing stationary phase) between the movable seal  16  and the second coupler seal  22 , in a manner such that the first opening  14  fluidly communicates with the second opening  18  through the first chromatography column  28 , the third and fourth openings  24 ,  26  (through lumen  27 ) and the second chromatography column  30 . According to an embodiment of this presentation, the first seal  12 , the first coupler seal  20 , the movable seal  16  and the second coupler seal  22  are all compression seals. 
     It is noted that in the Description above the first chromatography column  28  is described as a filter column, a pre-column, a guard column or a stationary phase column and the second chromatography column  30  is a containing stationary phase, but that the first chromatography column  28  could be a column containing stationary phase with the second chromatography column  30  being a filter column, a pre-column, a guard column or a stationary phase column, or that both columns could be stationary phase columns. 
     According to an embodiment of this presentation, the movable seal  16  can be arranged to move between a rest position (illustrated and described hereafter in  FIGS. 2-6 ), where it is possible to remove, install or replace one or both of the chromatography columns  28 ,  30  in the clamp, and a work position (illustrated in  FIG. 1 ), where the clamp presses the first chromatography column  28  between the first seal  12  and the first coupler seal  20  and presses the second chromatography column  30  between the movable seal  16  and the second coupler seal  22 . 
     According to an embodiment of this presentation, the first opening  14 , the first chromatography column  28 , the third opening  24 , the fourth opening  26 , the second chromatography column  30  and the second opening  18  can be coaxially aligned when in the work position. 
     According to an embodiment of this presentation, a lever  36  can be configured for actuating the movable seal  16  between the rest and work positions. As illustrated in  FIG. 1 , lever  36  can be coupled to movable seal  16  via a cam mechanism  37  that transforms a rotation of lever  36  around an axis  33  perpendicular to the clamp axis  35  into a translation of movable seal  16  along the clamp axis. It is to be noted that, due to perpendicular axis  33  being referenced to cam mechanism  37 , perpendicular axis  33  is not fixed but moves for example along an arc of a circle as lever  36  rotates around perpendicular axis  33 . 
     According to an embodiment of this presentation, lever  36  can form a cover preventing access to the first and second chromatography columns  28 ,  30  in the work position, as illustrated in  FIG. 1 , and allowing access to the first and second chromatography columns in the rest position, as illustrated in  FIGS. 2-6 . 
     According to an embodiment of this presentation, cam mechanism  37  can be arranged such that a reduced release force is exerted by the clamp on the lever at the beginning of a motion of lever  36  away from its work position; a larger release force being exerted by the clamp on the lever later along the motion of lever  36 , for example when the lever  36  is moved a predetermined angle away from its work position. The predetermined angle can be comprised between 5 and 15 degrees, but other angles can be successfully used. The predetermined angle can be of 10 degrees. According to an embodiment of this presentation, a magnet  41  can be arranged to retain lever  36  in the work position. 
     According to an embodiment of this presentation, the movable seal  16  can be arranged in a first section of a tube  44 ; a side portion (top side in  FIG. 1 ) of the tube  44  being removed from the end of the tube proximal the first seal  12  to a location proximal the movable seal  16  so that the tube  44  forms an open ended trough capable of receiving the second chromatography column  30 . According to an embodiment of this presentation, a full diameter of tube  44  can be kept intact along a length  45  between the movable seal  16  and the beginning of the trough to allow maintaining radial alignment of the second chromatography column  30  against the movable seal  16 . In additional embodiments, different shapes can be used for the tube  44  and open ended trough, such as a tube shape having 3, 4, 5, 6, 7, 8 or more sides, and the trough can be flat or comprise a number of flat surfaces. In some embodiments, the trough can be absent. In some embodiments, the tube  44  can fit inside the second chromatography column  30  or can fit around chromatography column  30 . 
     According to an embodiment of this presentation, the first seal  12  can be arranged to resiliently exert pressure (or force) on the first chromatography column  28 , the first coupler seal  20  and the coupler  19  and optionally to the second coupler seal  22 , the second chromatography column  30  and the movable seal  16  when the clamp is in the work position. In some embodiments, the pressure exerted by the first seal  12  can be a controlled pressure. In some embodiments, the controlled pressure can be achieved by axially mounting first seal  12  on a spring  34  or other resilient feature. The spring  34  or other resilient feature can exert a force directly or indirectly to the first seal  12 . In some embodiments, the spring  34  can be configured to apply an adjustable force to the first seal  12  or to controllably change the force resiliently exerted by the first seal  12 . According to an embodiment of this presentation, the first and second chromatography columns  28 ,  30  can have first and second lengths comprised in first and second lengths ranges. In some embodiments, spring  34  can be actuated to change the pressure resiliently exerted by the first seal  12  if the length or length range of the chromatography columns is changed. In some embodiments, spring  34  can comprise or be a Belleville spring or a coil spring or a wave spring or a leaf spring or a torsion spring or another type of spring. In some embodiments, spring  34  can comprise or be a resilient material, either solid or porous. In some embodiments, one or more of the coupler seals and in particular the first and second coupler seals  20 ,  22  can have axial resiliency, either due to the material they are made from or to a resilient mounting (not shown). 
     According to an embodiment of this presentation, clamp  10  can comprise a first retainer  32  for retaining the first chromatography column in contact with the first seal  12 . In some embodiments of a first retainer, the first retainer  32  can interconnectively interact with an end of the first chromatography column. In some such embodiments, the first retainer  32  can comprise a male portion optionally fitted with a frictional element arranged to frictionally cooperate with an inside diameter of a lumen  42  in the first chromatography column  28 . According to an embodiment of this presentation, the frictional element  32  can comprise an o-ring, as illustrated in  FIG. 1 . In some embodiments, the first retainer  32  can comprise a female portion optionally fitted with a frictional element. In some embodiments, the interaction between the first retainer  32  and the first chromatography column can be through a third part. 
     According to an embodiment of this presentation, clamp  10  can comprise a spring  47  for urging the movable coupler  19  toward the movable seal  16 . Movable coupler  19  thus can operate in some embodiments as a second retainer  19  that retains the second chromatography column  30  in contact with the movable seal  16 . According to an embodiment of this presentation, clamp  10  can be arranged such that in the rest position (described hereafter) movable coupler  19  is not in contact with the first chromatography column  28 , which can then be put in contact with (or removed from) the first seal  12  without moving the movable coupler  19 ; and such that the second chromatography column  30  can be arranged in contact with (or removed from) the movable seal  16  after moving the movable coupler away from the movable seal  16  to release the second chromatography column  30  from the movable coupler  19 . According to embodiments of this presentation, movable coupler  19  can be coupled to a carriage  49  arranged to slide axially along a rail  51  fixedly attached to the clamp  10 . 
     In some embodiments of this presentation, spring  47  can be replaced by gravity. In some embodiments of this presentation, for example if spring  47  is not present and movable coupler  19  is not urged toward movable seal  16 , clamp  10  can utilize another retainer to retain the second chromatography column  30  to the movable seal  16  in addition to or instead of the retaining function provided by movable coupler  19 . In some embodiments, such another retainer can comprise attachment(s) for attaching the second chromatography column  30  to the seal or to tube  44  or the trough in tube  44 . 
     According to an embodiment of this presentation, the first and second openings of clamp  10  can be respectively coupled to a fluid input pipe  38  and to a fluid output pipe  40 ; the fluid output pipe  40  can be sufficiently flexible for flexing without damage when movable seal  16  is actuated between the rest and work positions. According to an embodiment of this presentation, fluid input pipe  38  can be placed in thermal communication with a heater or cooler  39 , such as by winding the fluid input pipe around a heater or cooler  39  provided for controlling the temperature of the fluid sent into the first chromatography column. In some embodiments one or more of the fluid output pipe  40  and fluid input pipe  38  can be a metallic tube or a plastic tube. Suitable materials for the fluid output pipe  40  and/or the fluid input pipe can be selected from among materials such as corrosion resistant metals (e.g. stainless steels, nickel, nickel alloys, titanium, titanium alloys, etc., the composition and grades of such metals can be found on the websites and publications of manufacturers of metals, tubing and chromatography systems and are incorporated by reference herein) and plastics (e.g. PEEK, PTFE, PE, PP, PEEKsil, etc. the composition and grades of such plastics can be found on the websites and publications of manufacturers of plastics, tubing and chromatography systems and are incorporated by reference herein.) 
       FIG. 2  shows an embodiment of clamp  10  of  FIG. 1  in the rest position and shows lever  36  rotated into the open position (e.g. away from the first and second chromatography columns  28 ,  30 .) According to an embodiment of this presentation, rotating the lever  36  into the open/rest position (e.g. away from the first and second chromatography columns  28 ,  30 ) can cause cam mechanism  37  to axially move movable seal  16  away from first seal  12 . In some embodiments, such as some embodiments where a spring  47  urges movable coupler  19  toward movable seal  16 , moving movable seal  16  away from first seal  12  also moves movable coupler  19  away from the first chromatography column  28  and first seal  12 . This allows access to first chromatography column  28 , and allows installing, removing and replacing first chromatography column  28 , such as by disengagement of the first chromatography column  28  from the first seal  12  and movement of the first chromatography column  28  away from clamp  10  to remove the first chromatography column  28 , and reversing this procedure to install the first chromatography column  28 . In some embodiments, the first chromatography column can be removed by movement of the first chromatography column along its longitudinal axis followed by movement of the first chromatography column away from the clamp  10  to remove the first chromatography column  28 , and reversing this procedure to install the first chromatography column  28 . 
     According to an embodiment of this presentation, in the rest position movable coupler  19  can be spaced apart from first chromatography column  28  by a distance  50  that is sufficient to allow a user to free the second chromatography column  30  from movable coupler  19  by moving (e.g. manually) movable coupler  19  toward first chromatography column  28 . Thus, a user can install, remove and replace the second chromatography column  30  in the rest position. 
       FIG. 3  is a top view of clamp  10  in the rest position, showing the second chromatography column  30 , maintained on trough tube  44  and in contact with the movable seal  16  (not shown) by movable coupler  19 ; the first coupler seal  20  of movable coupler  19  being at a distance  50  away from first chromatography column  28 . 
       FIG. 4  is an elevation view of clamp  10  in the rest position, showing the second chromatography column  30 , maintained on trough tube  44  and in contact with the movable seal  16  (not shown) by movable coupler  19 ; the first coupler seal  20  of movable coupler  19  being at a distance  50  away from first chromatography column  28 . 
       FIG. 5  is a cut-away view of the clamp for chromatography columns shown in  FIG. 4 , showing the elements described in particular in relation with  FIGS. 1 and 2 . 
     In some embodiments, a portion of the second chromatography column  30  can be accessible to the first chromatography column  28  through the mobile coupler  19 , so as to allow a direct fluid communication between the first chromatography column  28  and the second chromatography column  30 . In some embodiments, a portion of the second chromatography column  30  can extend through the mobile coupler  19 , where the first chromatography column  28  can connect to the second chromatography column  30 . In some embodiments, the end of the second chromatography column  30  that connects with the first chromatography column  28  can be located within mobile coupler  19  and the end of the first chromatography column  28  can enter the mobile coupler  19  to connect with the second chromatography column  30 . In some embodiments, the mobile coupler  19  can interact with an outer surface of the second chromatography column  30  at the end or be spaced back from the end of the second chromatography column  30  (e.g., wall, step, pin, extension, indentation, notch, etc.) such that the mobile coupler  19  provides a force urging the second chromatography column toward the movable seal  16 . 
       FIG. 6  is identical to  FIG. 5 , but with the first and second chromatography columns removed for ease of understanding. 
     The foregoing has been described in connection with various embodiments, features or elements from one embodiment may be combined with other embodiments without departing from the teachings of this disclosure. Further, the combinations of features between the respective embodiments are not necessarily limited thereto. Various embodiments of the disclosure have been described. These and other embodiments are within the scope of the disclosure. In addition, those skilled in this art will understand how to make further changes and modifications to the embodiments to meet their specific requirements or conditions. Such changes and modifications may be made without departing from the scope and spirit of the present disclosure. 
     The foregoing Detailed Description of exemplary and preferred embodiments is presented for purposes of illustration and disclosure. It is not intended to be exhaustive nor to limit what can be claimed to the precise form(s) described, but only to enable others skilled in the art to understand how the disclosure may be suited for a particular use or implementation. The possibility of modifications and variations will be apparent to practitioners skilled in the art. For example, in the description the claim comprises a single mobile coupler  19  that couples in series first and second chromatography columns  28 ,  30 , but one skilled in the art can easily modify the clamp to comprise one or more additional mobile couplers  19  to couple in series one or more additional chromatography columns. In such an occurrence, each additional mobile coupler  19  could be attached by a spring to a previous mobile coupler  19  so as to retain each additional chromatography column. 
     No limitation is intended by the description of exemplary embodiments which may have included tolerances, feature dimensions, specific operating conditions, engineering specifications, or the like, and which may vary between implementations or with changes to the state of the art, and no limitation should be implied therefrom. Applicant has made this presentation with respect to the current state of the art, but also contemplates advancements and that adaptations in the future may take into consideration of those advancements, namely in accordance with the then current state of the art and also encompasses equivalents as applicable. Reference to a claim element in the singular is not intended to mean “one and only one” unless explicitly so stated. Moreover, no element, component, nor method or process step in this presentation is intended to be dedicated to the public regardless of whether the element, component, or step is explicitly recited in the Claims. 
     Concepts 
     Concept 1. A clamp for chromatography columns, the clamp having a first seal with a first opening, a movable seal with a second opening and a movable coupler; the movable coupler having first and second coupler seals with communicating third and fourth openings; 
     the clamp being configured for pressing a first chromatography column between the first seal and the first coupler seal and pressing a second chromatography column between the movable seal and the second coupler seal, such that the first opening fluidly communicates with the second opening through the first chromatography column, the third and fourth openings and the second chromatography column. 
     Concept 2. The clamp of Concept 1, further comprising a first retainer for retaining the first chromatography column in contact with the first seal. 
     Concept 3. The clamp of Concept 1 or 2, wherein the movable coupler retains the second chromatography column in contact with the movable seal when the first chromatography column is not pressed against the first coupler seal. 
     Concept 4. The clamp of Concept 3, further comprising a spring for urging the movable coupler toward the movable seal, whereby the movable coupler maintains the second chromatography column against the movable seal. 
     Concept 5. The clamp of any one of Concept 1-4, wherein the first opening, the first chromatography column, the third opening, the fourth opening, the second chromatography column and the second opening are coaxially aligned when the clamp presses the first chromatography column between the first seal and the first coupler seal and presses the second chromatography column between the movable seal and the second coupler seal. 
     Concept 6. The clamp of any one of Concept 1-5, wherein said movable seal is configured to move between: 
     a rest position, where the first chromatography column is positionable in contact with the first seal and the second chromatography column is positionable in contact with the movable seal; and 
     a work position, where the clamp presses the first chromatography column between the first seal and the first coupler seal and presses the second chromatography column between the movable seal and the second coupler seal. 
     Concept 7. The clamp of Concept 6, wherein the first seal is configured to resiliently exert pressure on the first chromatography column, the first coupler seal, the coupler, the second coupler seal, the second chromatography column and the movable seal in the clamp work position. 
     Concept 8. The clamp of Concept 7, wherein the first seal is mounted on a spring having a controlled tension, configured to controllably change the pressure resiliently exerted by the first seal. 
     Concept 9. The clamp of any one of Concept 6-8, further comprising a spring for urging the movable coupler toward the movable seal; the clamp being configured such that in the rest position the first chromatography column can be arranged in contact with, or removed from, the first seal without moving the movable coupler and the second chromatography column can be arranged in contact with, or removed from, the movable seal after moving the movable coupler away from the movable seal. 
     Concept 10. The clamp of any one of Concept 1-9, wherein said first and second chromatography columns have first and second lengths comprised in first and second lengths ranges. 
     Concept 11. The clamp of any one of Concept 6-9, further comprising a lever for actuating the movable seal between the rest and work positions. 
     Concept 12. The clamp of Concept 11, wherein the lever forms a cover preventing access to the first and second chromatography columns in the work position and allowing access to the first and second chromatography columns in the rest position. 
     Concept 13. The clamp of any one of Concept 1-12, wherein the first and second openings are respectively coupled to a fluid input pipe and to a fluid output pipe. 
     Concept 14. The clamp of Concept 2, wherein the first retainer comprises a male portion fitted with a frictional element configured to frictionally cooperate with an inside diameter of a lumen in the first chromatography column. 
     Concept 15. The clamp of Concept 14, wherein the frictional element comprises an o-ring. 
     Concept 16. The clamp of any one of Concept 1-15, wherein the movable seal is located at a first end of a tube; a side portion of said tube being removed from the end of the tube closest to the first seal to about the movable seal so that the tube forms an open ended trough capable of receiving the second chromatography columns. 
     Concept 17. The clamp of any one of Concept 1-16, wherein the first seal is non-movable. 
     Concept 18. A chromatography column clamp arranged: 
     to receive two chromatography columns between a first compression seal and a movable compression seal; and 
     to press said two chromatography columns on opposite sides of a compression seal coupler by urging the movable compression seal toward the first compression seal. 
     Concept 19. The chromatography column clamp of Concept 18, wherein: 
     the first seal has a first opening; 
     the movable seal has a second opening; 
     the movable coupler has first and second coupler seals with communicating third and fourth openings; 
     the clamp being configured such that the first opening fluidly communicates with the second opening through the first chromatography column, the third and fourth openings and the second chromatography column when the clamp presses the two chromatography columns on opposite sides of the compression seal coupler. 
     Concept 20. The chromatography column clamp of Concept 19, further comprising a spring for urging the movable coupler toward the movable seal. 
     Concept 21. A method of clamping two chromatography columns in series, the method comprising: 
     receiving two chromatography columns between a first compression seal and a movable compression seal; and 
     pressing said two chromatography columns on opposite sides of a compression seal coupler by urging the movable compression seal toward the first compression seal.