Abstract:
A method of forming a column ( 100  and  200 ) for use with an analytical chemical instrument. The method includes placing a frit ( 102  and  202 ) in proximity to a distal end ( 110  and  210 ) of a tube ( 104  and  204 ) having an internal bore ( 106  and  206 ) adapted to receive packing material ( 108  and  208 ) for selectively interacting with an analyte of interest in a sample. The method further includes laser welding the frit to the tube and inserting packing material within the internal bore of the tube. A column formed in accordance with this method.

Description:
CROSS-REFERENCE TO RELATED APPLICATION  
       [0001]     This application claims the benefit of U.S. Provisional Application No. 60/538,617, filed Jan. 22, 2004, and entitled Laser Welded Frit, the disclosure of which is hereby expressly incorporated by reference. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention relates to columns for use with an analytical chemical instrument, the column adapted to receive packing material for selectively interacting with an analyte of interest in a sample, and more specifically to columns and methods of forming columns having a frit which is welded to a tube of the column.  
       BACKGROUND OF THE INVENTION  
       [0003]     A number of chemical analytical techniques utilize columns for detecting or measuring an analyte of interest. The columns each include a cylindrical tube of a particular length and inner diameter dictated by experimental requirements that are filled with selectively adsorbent packing materials. An analyte or mixture of analytes (the “sample”) dissolved in a solution (the “sample matrix”) is introduced at one end of the column, and then a carrier fluid is run through the column. The carrier fluid brings the sample matrix along with it.  
         [0004]     As analytes travel through and around the column packing material, the analytes interact with the column packing material to varying degrees according to the analytes&#39; chemical affinity for the packing material. The greater the affinity of a particular analyte for the packing material, the longer it will take for that analyte to travel the length of the column. Analytes that have no affinity whatsoever for the packing material will travel at approximately the same speed as the carrier solvent, while analytes with affinity for the packing material will be delayed by an amount generally proportional to that affinity. Therefore, a single analyte in solution can be separated from its sample matrix, or a mixture of analytes in solution can be separated both from the sample matrix and from each other, based on differing affinities for a given packing material. Such techniques are used in liquid chromatography (LC) as well as in situations where LC is combined with other instrumentation (liquid chromatography-mass spectrometry, or LCMS, for example).  
         [0005]     Most packing materials include either regular (spherical) or irregular particles, with a predetermined nominal diameter. Actual particle diameters are likely to be within a normal distribution around this predetermined nominal diameter. A design requirement of chromatography column hardware is that the hardware must allow liquids to pass into and out of the column, while keeping the packing material immobilized within the column tube. This is often accomplished by use of a porous substance called a “frit” disposed at an inlet end and at an outlet end of the column. This frit has a rated porosity that is smaller than that of the smallest expected packing material particles.  
         [0006]     The outlet frit of a column is more than just a barrier for keeping packing material in place. The frit actually plays an important role in determining overall column performance. Packing materials, particularly those that are formed from regular, spherical particles, must be placed into a column in a way that ensures the packing material is tightly packed and evenly distributed, without voids, channels, and other irregularities. Any deviance from a perfectly packed bed will reduce the effective separating power and performance of the analytical column. Columns are packed by sending packing material slurry through the column, which is open at the inlet. The slurry solvent passes through the outlet frit, while the packing material collects at the frit surface, gradually filling the column. And so the outlet frit is actually the foundation upon which the packed bed is built. Thus, the method used to retain the frit at the column outlet is preferably mechanically durable. It is also preferable that the seal between the frit and the column be as close to hermetic as practically possible. This ensures that the only possible flow path out of the column is through the frit. Internal volumes should also be kept as low as possible to minimize “mixing” effects, which can serve to decrease instrument sensitivity and response.  
         [0007]     Previously developed columns are manufactured with one of a few methods for keeping outlet frits in place. A frit can be placed at the surface of a tube and secured via an external compression fitting. Or, the frit can be placed within the tube diameter and secured there. This second approach is desirable in terms of keeping internal volumes to a minimum.  
         [0008]     Current methods employed in securing frits within the inner diameter of column tubes include: 
        Interference fit, where the diameter of the frit is selected to be slightly larger by a precise amount than the inner diameter of the tubing, and the frit is forcibly pressed into the smaller cavity, resulting in a friction fit;     Adhesive bonding, where a chemical adhesive is used to provide a bond between the frit and the inner tube wall;     Staking, either a roll-stake or orbital stake method, where the frit is placed within a counter-bored cavity with a thin wall at the end of the tube, and this thin walled material is then rolled over the side and front edge of the frit;     Sintering, where the frit is actually produced in situ within the tube end, rather than being manufactured separately;        
 
         [0013]     Controlled atmosphere brazing, where the frit is brazed onto the end of tube in a controlled atmosphere; and 
        Welding, where, referring to  FIG. 1 , a frit  12  is welded onto a distal end of a tube  14  to form a column  10 . This is accomplished by inserting a porous frit  12  into a recess  16  disposed in a distal end of the tube  14 . A ring of solder  18 , such as silver, is placed along an upper edge of an annular space  20  disposed between the frit  12  and the tube  14 . The column  10  is placed in an inert environment and heated, such as by placing the column  10  in an oven, to cause the solder  18  to melt. The melted solder  18  flows in the annular space  20  as shown in  FIG. 2 . As the solder  18  cools, the outer surface of the frit  12  is bonded to the inner surface of the tube  14  by the solder  18 .        
 
         [0015]     The current trend in column hardware technology is toward smaller bed volumes. It is typical for a given sample to be present in very low amounts, or in very low concentrations. Keeping internal volume to an absolute minimum is necessary to avoid dilution of the sample during analysis. Some of the above methods of frit retention are not amenable to use in low-volume applications, while others have limitations and drawbacks of a different kind. Problems of previously developed frit coupling techniques include: 
        Sample contamination potential from the adhesives used to adhere the frit to the tube;     Non-hermetic seal formed when the frit is attached using staking and interference fit techniques;     Residue left within the tube when in situ sintering techniques are used; and     Referring to  FIG. 2 , when welding frits  12  to tubes  14  using previously developed welding techniques, the welding must occur in an inert environment to prevent welding residues from contaminating the column  10 , thereby increasing the difficulty and expense of welding the frit  12  to the tube  14 . Further, it has been found that previous welding techniques are imprecise and unsuitable for frit  12  diameters less than about 0.25 of an inch since the flow of the solder  18  cannot be accurately controlled and may flow into a central bore  22  of the tube  14  interfering with a flow of a sample through the column  10 . Further, previously developed welding techniques do not substantially reduce the porous volume of the frit  12  since the solder  18  only adheres to the outer surface of the frit  12  and does not fill in more than a negligible amount, if any, of the pores of the frit  12 . Thus, the relatively large porous volume of the frit  12  absorbs a portion of the sample passing through the column  10  creating a dead space in a column  10 , thereby introducing error into the testing process and increasing the amount of sample needed to perform the test.        
 
         [0020]     Thus, there exists a need for a column having a frit attached to a tube of the column that is reliable, relatively inexpensive, reduces testing error, and which does not contaminate a sample passing through the column.  
       SUMMARY OF THE INVENTION  
       [0021]     One embodiment of a column formed in accordance with the present invention for use with an analytical chemical instrument, the column adapted to receive packing material for selectively interacting with an analyte of interest in a sample is disclosed. The column includes a tube having a bore adapted to receive a packing material and a distal end. The column also includes a frit coupled to the distal end of the tube for retaining the packing material within the tube while permitting the analyte of interest to pass there through. The column further includes a laser weld coupling the frit to the tube.  
         [0022]     One embodiment of a method performed in accordance with the present invention for forming a column for use with an analytical chemical instrument is disclosed. The method includes placing a frit in proximity to a distal end of a tube having an internal bore adapted to receive packing material for selectively interacting with an analyte of interest in a sample. The method further includes welding the frit to the tube and inserting packing material within the internal bore of the tube. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0023]     The foregoing aspects and many of the attendant advantages of this invention will become better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein:  
         [0024]      FIG. 1  is a cross-sectional view of a prior art column showing a distal end of a tube prior to melting of a ring of solder;  
         [0025]      FIG. 2  is a cross-sectional view of the prior art column of  FIG. 1  showing the distal end of the tube after melting of the ring of solder, thereby bonding the frit to the distal end of the tube;  
         [0026]      FIG. 3  is an exploded elevation view of one embodiment of a column formed in accordance with the present invention showing a frit prior to laser welding of the frit to a distal end of a tube;  
         [0027]      FIG. 4  is a partial cross-sectional view of the column of  FIG. 3  taken vertically through a centerline of the column showing the frit during laser welding of the frit to the tube;  
         [0028]      FIG. 5  is a partial cross-sectional view of the column of  FIG. 3  taken vertically through the centerline of the column showing the frit after laser welding of the frit to the tube;  
         [0029]      FIG. 6  is an exploded elevation view of an alternate embodiment of a column formed in accordance with the present invention showing a frit prior to laser welding of the frit within a recess disposed in a distal end of a tube;  
         [0030]      FIG. 7  is a partial cross-sectional view of the column of  FIG. 6  taken vertically through a centerline of the column showing the frit during laser welding of the frit within the recess of the tube; and  
         [0031]      FIG. 8  is a partial cross-sectional view of the column of  FIG. 3  taken vertically through the centerline of the column showing the frit after laser welding of the frit within the recess of the tube. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0032]     One embodiment of a column  100  formed in accordance with the present invention is shown in  FIGS. 3-5 . Turning to  FIG. 3 , the column  100  includes two main components, a frit  102  and a tube  104 . The tube  104  is a cylindrical structure of a predetermined length. The tube  104  includes a column bore  106  passing along a centerline of the tube  104 . Referring to  FIG. 5 , the column bore  106  has an inner diameter  107  dictated by experimental requirements for receiving selectively adsorbent packing material  108 . In the illustrated embodiment, the bore has a diameter  107  that is approximately 0.006 of an inch, though it should be apparent to those skilled in the art that the diameter of the column bore  106  may be greater or less than the illustrated and described diameter  107 , with a few suitable examples being diameters ranging from about 0.002 of an inch to about 0.181 of an inch (4.6 millimeters). The tube  104  may be formed from a rigid material amenable to laser welding, such as a metal, one suitable example being 316L low carbon stainless steel.  
         [0033]     The packing material  108  is selected to interact with the analytes of interest to varying degrees according to the analytes&#39; chemical affinity for the packing material. The packing material  108  permits a single analyte in solution to be separated from its sample matrix, or a mixture of analytes in solution to be separated both from the sample matrix and from each other, based on differing affinities for the selected packing material  108 . Most packing materials are formed from either regular (spherical) or irregular particles, with a predetermined nominal diameter, one suitable nominal diameter being 5 microns. Of note, for the purpose of clarity, the individual particles of the packing material  108  are greatly enlarged for illustrative purposes in the figures. It should be apparent to those skilled in the art that the particles in an actual embodiment are much smaller relative to the diameter  107  of the column bore  106  than shown in the figures.  
         [0034]     The packing material  108  is retained within the bore  106  by the frit  102 . The frit  102  allows liquids to pass into and out of the column  100 , while keeping the packing material  108  immobilized within the column bore  106  of the tube  104 . The frit  102  is formed from a porous material and has a rated porosity that is smaller than that of the smallest expected packing material particles  108  such that the packing material  108  is retained within the bore  106  while the sample and analyte is allowed to pass through the frit  102 . In the illustrated embodiment, the frit  102  is formed from a rigid material amenable to laser welding, such as a sintered metal, one suitable example being 316L low carbon stainless steel having a rated porosity that is smaller than that of the smallest expected packing material particles  108 . The frit  102  preferably has an outer diameter substantially equal to that of the tube  104 . Although the frit  102  may be of any diameter, the process described herein is suitable with frits having small diameters here before unable to be welded, such as diameters of less than about 0.25 of an inch, one suitable example being diameters less than about 0.1 of an inch.  
         [0035]     Referring to  FIG. 4 , during manufacturing of the column  100 , the frit  102  is positioned to abut against a distal, square cut end  110  of the tube  104 . A laser beam  112  is directed from a laser beam generator  113  and directed by a beam-directing optic (not shown) to selectively focus the laser beam  112  upon the frit  102  and the distal end  110  of the tube  104  to laser weld the frit  102  to the tube  104 . The laser welding of the frit  102  may be performed in a non-inert environment.  
         [0036]     Turning to  FIGS. 4 and 5 , by selectively controlling the spot size and power density of the laser beam  112 , a penetration depth and width of the laser beam  112  is precisely controlled. This permits the precise and selective conversion of a volume of the frit  102  from a porous state (the original porous material of the frit  102  prior to application of the laser) to a substantially non-porous state (the laser weld  118  formed by melting porous material of the frit  102 ). The laser beam  112  is selectively controlled to leave a porous passage  116  through the frit  102  having a diameter substantially equal to the diameter of the bore  106  passing through the tube  104 , one suitable example being between about 0.002 inches and about 0.2 inches. Stated in other words, the laser beam fuses the frit  102  to the axial distal end  110  of the tube  104  and closes the pores in the frit  102  where the fusing takes place, converting the porous material of the frit  102  to a substantially non-porous laser weld  118 . Once the laser welding process is complete, the diameter of the porous metal of the frit  102  is reduced to approximately the same diameter as the column bore  106 .  
         [0037]     Further, the porous volume of the frit  102  is greatly reduced by the welding process. Moreover, before laser welding, the volume of the frit is occupied completely by porous material. After welding, the volume of the frit that is porous is reduced by about 10%, 50%, 75%, 90%, or 95% or more, and the remaining volume of the frit  102  is occupied by the substantially non-porous laser weld  118 . The performance of the resulting packed bed  120  is vastly improved with the reduced volume of the porous portion of the frit  102  since the sample will be focused in a porous passage passing  116  through the frit  102  having substantially the same diameter  107  as the packed bed  120  keeping band broadening to a minimum.  
         [0038]     Once the frit  102  is welded in place, the column  104  is packed by sending packing material slurry through the column, which is open at an inlet. The slurry solvent passes through the frit  12 , while the packing material  108  collects at an inboard surface of the frit  102 , gradually filling the column bore  106 , forming the packed bed  120 . Thus, the frit  102  acts as the foundation upon which the packed bed  120  is built. Inasmuch as the frit  102  is laser welded to the tube  104 , the coupling of the frit  102  to the tube  104  is mechanically durable. Further, the coupling of the frit  102  to the tube  104  by laser welding provides a seal between the frit  102  and tube  104  that is hermetic. This ensures that the only possible flow path out of the column is through the porous passage  116  in the frit  102 . This also helps to ensure that internal volumes are kept as low as possible to minimize “mixing” effects, which can serve to decrease instrument sensitivity and response. This also keeps total flow-through volume to a minimum. Further, the walls of the column bore  106  of the tube  104  above the frit  102  is not altered or affected by the welding process. Additionally, the dead volume between the frit  102  and the tube  104  is minimized since the frit  102  is fused to the tube  104  at the junction of the frit  102  with the tube  104 .  
         [0039]     Referring to  FIG. 5 , during use, a sample containing an analyte of interest is injected in the column bore  106  and passed through the packed bed  120 . The frit  102  impedes the packing material  108  from leaving the column bore  106  while permitting the sample to pass through the porous passage  116  in the frit  102  to the analytical instrument (not shown) for analysis.  
         [0040]     Referring to  FIGS. 6-8 , an alternate embodiment of a column  200  formed in accordance with the present invention is shown. The column  200  is substantially similar to the column  100  depicted and described in relation to  FIGS. 3-5 . Therefore, for the sake of brevity, this detailed description will focus only upon the differences between the two embodiments.  
         [0041]     Turning to  FIG. 6 , generally stated, the difference between the embodiment of  FIGS. 3-5  and the alternate embodiment of  FIGS. 6-8  is that a frit  202  of the column  200  of the alternate embodiment is placed within a recess  250  disposed in a distal end of a tube  204  of the column  200  instead of abutting the frit against a square cut distal end of the tube as is shown and described for the embodiment of  FIGS. 3-5 . The recess  250  for receiving the frit  202  is preferably cylindrical in shape and may be countersunk as shown in the illustrated embodiment. The frit  202  is correspondingly shaped to be received within the recess  250 . Although the frit  202  is illustrated and described as having a countersunk end correspondingly shaped relative to the recess  250 , it should be apparent to those skilled in the art that the frit  202  may be alternately shaped, one suitable example being wherein the frit  202  is cylindrical in shape without having a matching frustoconical end to match the countersunk shape of the recess  250  in the tube  204 . The frit  202  has a diameter  252  that is less than the outer diameter of the tube  204  such that an annular retaining wall  254  is formed at the distal end  210  of the tube  204  for at least partially housing the frit  202 .  
         [0042]     Referring to  FIG. 7 , like the previous embodiment, a laser beam  212  is emitted from a laser beam generator  213  for forming a laser weld  218  for laser welding the frit  202  within the recess  250  and to the tube  204 , while leaving a porous passage  216  (see  FIG. 8 ) passing through the frit  202 . Turning to  FIG. 8 , a packing material  208  is then placed within a column bore  206  of the tube  204  to form a packed bed  220  as shown and described above.  
         [0043]     The operation of the column  200  of  FIGS. 6-8  is identical to the operation of the column  100  of  FIGS. 3-5 , and therefore for the sake of brevity, will not be redundantly described herein.  
         [0044]     While the preferred embodiment of the invention has been illustrated and described, it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention.