Patent Publication Number: US-2007116611-A1

Title: Fraction collection system

Description:
RELATED APPLICATIONS  
      This patent application claims the benefit of U.S. provisional patent application Ser. No. 60/736,448 filed on Nov. 14, 2005. 
    
    
     BACKGROUND  
      Chromatography is one example of an analytical chemistry system that can employ a fraction collection system. Chromatography is used to analyze the constituents, or fractions, of a sample of interest, and, in some cases, to collect each of the fractions of the sample of interest separately for further analysis or use. Chromatography generally relates to any of a variety of techniques used to separate complex mixtures based on the differential affinities of the fractions of the sample for a mobile phase with which the sample flows, and a stationary phase through which the sample passes.  
      Generally, liquid chromatography includes a stationary phase that includes a finely powdered solid adsorbent packed into a chromatography cartridge or column, and the mobile phase includes one or more eluting solvents that are moved through the cartridge by a pump. The sample to be analyzed by liquid chromatography is injected into the cartridge and monitored by a detector. The detector provides identification and/or differentiation of the fractions as the fractions elute from the cartridge. One type of liquid chromatography, flash chromatography, includes a cartridge (in some cases, a disposable cartridge) filled with the stationary phase (e.g., silica gel), and the sample to be separated is placed on top of the stationary phase. The cartridge is filled with an isocratic or gradient solvent which, with the help of pressure, enables the sample to run through the cartridge and become separated. Liquid chromatography, and particularly, flash chromatography can be used for a variety of applications, including, but not limited to, drug discovery, sample clean-up, and natural product purification, among others.  
     SUMMARY  
      The present invention relates to a fraction collection system for use in the field of chemistry, and particularly, for use in the field of analytical chemistry. Fraction collection systems can be used to separate and collect the constituents, or fractions, of a variety of samples. Fraction collection systems can be used to produce an end product, or an intermediate product that can be further manipulated, investigated, or analyzed. Fraction collection systems can be used to aliquot a larger volume of fluid into multiple smaller volumes of fluids, such that each fraction includes the same chemical makeup as the other fractions. In addition, fraction collection systems can be used to collect fractions of a sample that have been identified and separated (e.g., by an upstream process, such as a chromatography process) as having a different chemical makeup.  
      In one embodiment, the invention provides a fraction collection system operable with an analytical chemistry system. The fraction collection system includes a first fraction collector having a frame, an adapter tray configured to slide between a first position and a second position with respect to the frame, and a collection rack configured to support at least one receptacle. The collection rack is movable with respect to the frame between the first position and the second position.  
      In another embodiment, the invention provides a fraction collection system configured for chromatography processes. The fraction collection system includes a first fraction collector having a first frame, a first adaptor tray that slides with respect to the first frame, and a first collection rack supported by the first adaptor tray. The fraction collection system also includes a second fraction collector having a second frame, a second adaptor tray that slides with respect to the second frame, and a second collection rack supported by the second adaptor tray. The first fraction collector is coupled to the second fraction collector for performing chromatography processes in at least one of the first fraction collector and the second fraction collector.  
      Other aspects of the invention will become apparent by consideration of the detailed description and accompanying drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1  is a perspective view of a fraction collection system according to one embodiment of the present invention, including a plurality of stackable fraction collectors.  
       FIG. 2  is a perspective view of a portion of one of the stackable fraction collectors.  
       FIG. 3  is a perspective view of an adapter tray of one of the stackable fraction collectors. 
    
    
     DETAILED DESCRIPTION  
      Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings, but can include, for example, electrical and fluid connections or couplings.  
      Although directional references, such as upper, lower, downward, upward, rearward, bottom, front, rear, etc., may be made herein in describing the drawings, these references are made relative to the drawings (as normally viewed) for convenience. These directions are not intended to be taken literally or limit the present invention in any form. In addition, terms such as “first”, “second”, and “third” are used herein for purposes of description and are not intended to indicate or imply relative importance or significance.  
       FIG. 1  illustrates a fraction collection system  5  according to one embodiment of the present invention. By way of example only, the fraction collection system  5  illustrated in  FIG. 1  is shown as being coupled to a chromatography system  6 . However, it should be understood that the fraction collection system  5  of the present invention can be used with a variety of other systems, including other chemistry systems, such as other analytical chemistry systems.  
      The fraction collection system  5  can include one or more stackable fraction collectors  10 . In the embodiments illustrated in  FIG. 1 , the fraction collection system  5  includes three stackable fraction collectors  10 . However, three fraction collectors  10  are illustrated in  FIG. 1  by way of example only to illustrate their stackable nature. It should be understood that the actual number of fraction collectors  10  in any given fraction collection system  5  can vary (i.e., can be more or less than three). Each fraction collector  10  of the illustrated embodiment includes a frame  12 , a controller  14 , a first arm  15  having a track  24  defined therein, a second arm  16  movable with respect to the first arm  15  via the track  24 , a nozzle  18  coupled to the second arm  16 , and an adapter tray  20  that supports a collection rack assembly  21 . Each collection rack assembly  21  can include one or more collection racks  22 .  
      The frame  12  can be formed of a variety of materials, including, without limitation, at least one of metal, plastic, ceramic, a composite material, or any other suitable material. The frame  12  supports the first arm  15  and the second arm  16  near the top of the fraction collector  10 , and supports the adapter tray  20  near the bottom. The frame  12  can include any of a variety of structures, such as protrusions, recesses, or combinations thereof to allow the fraction collectors  10  to be stacked by inter-engagement of such structures. For example, in some embodiments, as shown in  FIG. 1 , the top of the frame  12  includes protrusions  26  and the bottom of the frame  12  includes complementary recesses (not shown) to secure the frames  12  with respect to one another when stacked. The stackability and modularity of the fraction collectors  10  of the fraction collection system  5  allows the entire fraction collection system  5  to consume less total area of highly valuable floor or lab-bench space than if the fraction collectors  10  were arranged on the same support surface (e.g., side-by-side).  
      In some embodiments of the present invention, the fraction collection system  5  includes a controller  14  adapted to control the one or more fraction collectors  10 . In some embodiments, as shown in the illustrated embodiment, each fraction collector  10  includes a dedicated controller  14 . The controller  14 , whether dedicated or universal, provides instructions to control the motion of the second arm  16  of each fraction collector  10  to control the separation and collection of fractions of a sample of interest. In embodiments employing dedicated controllers  14 , as shown in  FIG. 1 , each controller  14  includes an input connection  28  and an output connection  30 . The input connection  28  allows the controller  14  to receive instructions based on the chromatography analysis being performed. These instructions may come from a variety of suitable sources of instruction, including, but not limited to, a controller or microprocessing unit  32 , which may be a part of, or used in conjunction with, the chromatography system  6 , or any other suitable sources of instruction. The output connection  30  allows fraction collectors  10  to be connected in a series configuration by passing instructions to the input connection  28  on another fraction collector  10 . This permits single large chromatography processes to be run across multiple fraction collectors  10  if the number of fractions to be collected exceeds the number of receptacles  34  allocated to one fraction collector  10 . As a result, the fraction collection system  5  may be used to continuously run an infinitely long fraction collection process (e.g., a chromatography process) with as few as two fraction collectors  10 , provided a user replaced the collection racks  22  as they became full and the corresponding fraction collector  10  became temporarily inactive. As a result, the fraction collection system  5  is configurable to match the capacity desired for any given fraction collection process.  
      In some embodiments, the fraction collectors  10  of the fraction collection system  5  are connected in parallel so that different tests can be run simultaneously using the individual fraction collectors  10  of one fraction collection system  5 . In such embodiments, each fraction collector  10  will receive its own set of instructions to the input connection  28  on the controller, rather than receiving instructions from the output connection  30  of another fraction collector  10 . Some embodiments of the present invention can include a combination of fraction collectors  10  connected in series and fraction collectors  10  connected in parallel.  
      The nozzle  18  can be fluidly coupled to a detector (e.g., a UV detector) of the chromatography system  6 . The fractions of a sample of interest can be separated by passage through one or more chromatography cartridges, identified by a detector, and sent to the fraction collection system  5  to be collected. The fractions can be sent to any nozzle  18  of the fraction collection system  5 , or to waste, as instructed by a user or peak detection software (also sometimes referred to as fraction collection software). The controller  14  can include at least rudimentary peak detection software, and/or the controller  14  can be adapted to receive instructions from external peak detection software of the chromatography system  6 . When a fraction is sent to a nozzle  18 , the controller  14  operates the second arm  16  to move the nozzle  18  to a position above a desired receptacle  34 .  
      As shown in  FIG. 1 , a first end of the first arm  15  is coupled to an upper portion of the frame  12 , and a second end of the first arm  15  is cantilevered over the collection rack assembly  21 . The nozzle  18  is coupled to a first end of the second arm  16 . The nozzle  18  is directed downwardly and is adapted to dispense collected fractions into receptacles  34 . A second end of the second arm  16 , opposite the first end, is coupled to the first arm  15 , and particularly, to the track  24  defined by the first arm  15 . To access all of the receptacles  34  in a collection rack  22 , the second arm  16  is rotationally and translationally movable relative to the first aim  15  in a polar coordinate system. To accomplish this, the length of the track  24  can be greater than the length of the second arm  16 . The controller  14  can receive r and θ coordinates (e.g., from the controller  32 ) corresponding to the location of a destination receptacle  34  for a given fraction, and the controller  14  can activate the second arm  16  (e.g., via activation of a motor) to move relative to the first arm  15  accordingly. The second arm  16  can be moved in a linear direction along the track  24 , and can also pivot about a connection point between the first arm  15  and the second arm  16 . As a result, the nozzle  18  can be positioned above any desired receptacle  34  by a combination of translational and/or rotational motions. A variety of coordinate systems can be employed to control the movement of the nozzle  18  relative to the receptacles  34 . For example, other embodiments of the present invention may include a two or three dimensional Cartesian coordinate system for positioning the nozzle  18  over a desired receptacle  34  for expulsion of one or more fractions.  
      Referring to  FIG. 3 , the adapter tray  20  is generally flat and includes an upper surface  44  that defines one or more recesses  40 . The adapter tray  20  can be formed of a variety of materials, including, but not limited to, at least one of metal, ceramic, plastic, a composite material, or any other suitable material. As shown in  FIG. 2 , the collection rack assembly  21  includes three collection racks  22 . Accordingly, the adapter tray  20  includes three recesses  40 , each dimensioned to receive a collection rack  22 . Other embodiments of the adapter tray  20  may include any variety and combination of recesses, protrusions, apertures, demarcations, sensors, and the like, to accommodate one or more collection racks  22  from different manufacturers. That is, the adapter tray  20  can be removable and replaceable to allow other adapter trays to be used with the fraction collection system  5  that are adapted to hold other collection racks  22  of a different configuration. As a result, the fraction collection system  5  can be configured to be used with any manufacturer&#39;s collection racks  22 . In some embodiments, the fraction collection system  5  can be packaged as a kit with customer-specific adapter tray(s)  20 . In other embodiments, the fraction collection system  5  can come equipped with a variety of adapter trays  20  to allow a user to adapt his/her fraction collection system  5  as he/she desires. In still other embodiments, the fraction collection system  5  can include a single adapter tray  20  with a variety of recesses, protrusions, apertures, demarcations, sensors, and the like, to allow the single adapter tray  20  to be used to support a multitude of different collection racks  22  from different manufacturers.  
      In some embodiments, each adapter tray  20  is stationary with respect to the frame  12  and supports the collection rack assembly  21 . However, in some embodiments, as shown in  FIGS. 1 and 2 , the adapter tray  20  is slidable with respect to the frame  12  (e.g., similar to a drawer) to facilitate the observation of samples, the removal or exchange of collection racks  22 , and/or the removal or exchange of receptacles  34 . The collection rack assembly  21  of the top fraction collector  10  illustrated in  FIG. 1  is shown as being slid out into a “setup” position, while the collection rack assemblies  21  of the other two fraction collectors  10  illustrated in  FIG. 1  are shown in an “operating” position. The slidable nature of the adapter tray  20  into the “setup” position facilitates access of any portion of the collection rack assembly  21 , while still allowing the collection rack assembly  21  to be supported by the frame  12  of the fraction collector  10 . In other words, the slidability of the adapter tray  20  facilitates access of the collection rack assembly  21  without requiring that the collection rack assembly  21  be removed and held or placed upon another support surface. As a result, the slidability of the adapter tray  20  of each fraction collector  10  provides an additional space-saving mechanism, such that each fraction collector  10  takes up less valuable floor or lab-bench space than if the collection rack assembly  21  had to be removed, in part or in whole, from each fraction collector  10 . The “operating ” position allows the collection rack assembly  21  to be ready to receive fractions of a sample of interest during operation of the fraction collector  10 .  
      In some embodiments, as shown in the illustrated embodiment, the frame  12  includes one or more tracks  45  dimensioned to receive at least a portion of the adapter tray  20  to allow the adapter tray  20  to slide relative to the frame  12 . In some embodiments, as shown in  FIGS. 1 and 2 , the fraction collector  10  can include a sliding mechanism  46  coupled to two opposing sides of the adapter tray  20  and dimensioned to be received within the tracks  45  of the frame  12  to allow the adapter tray  20  to slide in and out of the frame  12  below the first and second arms  15 ,  16 , and the nozzle  18 . In some embodiments, the sliding mechanism  46  can be adapted to inhibit the complete removal of the adapter tray  20  from the frame  12  to prevent dropping the adapter tray  20  or the collection rack assembly  21 . In some embodiments, each fraction collector  10  includes a plurality of independently slidable adapter trays  20 , such that a portion of the collection rack assembly  21  can be accessed, removed and/or exchanged without disturbing the other portions of the collection rack assembly  21  or a fraction collection process. In such embodiments, the fraction collector  10  may be used to continuously run an infinitely long chromatography process with as few as two independently slidable adapter trays  20 , provided a user replaced the collection racks  22  (or portions thereof) corresponding to each slidable adapter tray  20  as they became full.  
      The sliding mechanism  46  is shown in the illustrated embodiment by way of example only. Other embodiments may employ other types of sliding mechanisms, such as an ACCURIDE®-brand drawer slide (e.g., Model No. 2907, available from Accuride International Inc., Santa Fe Springs, Calif.).  
      The collection rack assembly illustrated in  FIG. 2  includes three identical collection racks  22 . Each collection rack  22  includes an upper divider  50 , a lower divider  52 , and a base plate  54 . As shown in  FIG. 2 , the recesses  40  of the adapter tray  20  are slightly larger than the perimeter of the base plate  54 , such that each collection rack  22  can be positioned in a recess  40  of the adapter tray  20 . Each collection rack  22  of the illustrated embodiment includes a plurality of apertures  56 , and each aperture  56  is dimensioned to receive a receptacle  34 . In the illustrated embodiment, the upper and lower dividers  50 ,  52  have sixty uniformly sized and spaced apertures  56  dimensioned to receive sixty test tubes, respectively. The number and position of the apertures  56  in each collection rack  22  can vary, depending on the shape and size of the receptacles  34  used. The apertures  56  of the illustrated embodiment are shown by way of example only, and any suitable receptacle holding means can be employed to hold each receptacle  34  in the collection rack  22 . For example, recesses, grooves, or depressions can also be employed to receive and hold the receptacles  34  in the collection rack  22 .  
      The base plate  54  supports the receptacles  34 , and is shaped and dimensioned to fit within one of the recesses  40  on the adapter tray  20  to inhibit the collection racks  22  from moving or shifting with respect to the adapter tray  20 . The upper dividers  50  also include handles  58  to allow a user to grasp the collection rack  22  during placement or removal of the collection rack  22  from the adapter tray  20 . The upper divider  50 , lower divider  52 , and base plate  54  are coupled together and held at a constant distance from each other via standoffs  60 . The standoffs  60  are sufficiently rigid to resist shifting or rotating of the upper and lower dividers  50 ,  52  with respect to one another to maintain the receptacles  34  in a substantially vertical orientation. The collection racks  22  shown in the illustrated embodiment are shown by way of example only, and those of ordinary skill in the art should appreciate that the fraction collection system  5  is flexible to accommodate a variety of configurations, sizes and quantities of collection racks  22 .  
      Various features and advantages of the invention are set forth in the following claims.