Patent ID: 12222339

DETAILED DESCRIPTION

Reference in the specification to “one embodiment” or “an embodiment” means that a particular, feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the teaching. References to a particular embodiment within the specification do not necessarily all refer to the same embodiment.

The present teaching will now be described in more detail with reference to exemplary embodiments thereof as shown in the accompanying drawings. While the present teaching is described in conjunction with various embodiments and examples, it is not intended that the present teaching be limited to such embodiments. On the contrary, the present teaching encompasses various alternatives, modifications and equivalents, as will be appreciated by those of skill in the art. Those of ordinary skill having access to the teaching herein will recognize additional implementations, modifications and embodiments, as well as other fields of use, which are within the scope of the present disclosure as described herein.

This disclosure arises, in part, from the realization that apparatus can be provided for connecting chromatography columns without the use of hand tools (e.g., wrenches) or ferrules in such a way as to inhibit (e.g., prevent) carry-over, dispersion, or dead volume. In some cases, a fluid tight connection (e.g., up to at least 20,000 pounds per square inch) is provided which does not require the application of torque, such as is typical of conventional fluid fittings having threaded or bayonet connections, and/or which can allow for a quick and highly repeatable connection that does not require highly skilled operators to ensure that the connection is properly established. Further, it has been found that such an apparatus should be capable of accommodating different sized chromatography columns, thereby requiring a moving carriage part for making such accommodations. This disclosure further arises from the realization that such a carriage requires significant stability prior to actuating the connection with chromatography columns.

Systems described herein include apparatus for connecting fluidic tubing to a chromatography column to establish a fluid tight connection therebetween. The apparatus can provide a quick and highly repeatable fluid tight connection that does not require highly skilled operators to ensure that the connection is properly established. The apparatus allows for chromatography columns to be connected without the use of tools or ferrules and in such a way as to inhibit carry-over, dispersion, and dead volume. Various implementations of these systems relate to liquid-chromatography apparatus, for example, HPLC (High Performance Liquid Chromatography) and UPLC (Ultra Performance Liquid Chromatography) systems coupled to a mass spectrometer detection system. Further, the apparatus includes a carriage having a connection actuator that is separate from a carriage movement stop mechanism. This allows for the carriage to remain stable prior to initiation of the connection actuator and establishing fluidic connections with a chromatography column.

FIG.1shows an implementation of a liquid chromatography system10for separating a sample into its constituents. The liquid chromatography system10includes a solvent delivery system12in fluidic communication with a sample manager14. Generally, the solvent delivery system12includes pumps (not shown) in fluidic communication with solvent reservoirs from which the pumps draw solvents. The solvent delivery system12delivers a mixture of solvents to the sample manager14. The sample manager14is in fluidic communication with a sample source18from which the sample manager acquires and introduces a sample to the solvent mixture arriving from the solvent delivery system12.

In fluidic communication with the sample manager14is a column enclosure20for providing a controlled temperature environment for a chromatography column used in separating sample-solvent compositions. As described herein, the column enclosure20includes a fluidic coupling apparatus for establishing fluidic connections between chromatography components (e.g., between fluidic tubing and the chromatography column). From the column enclosure20, the constituents of the separated sample pass to a detector16or other equipment, for example, a mass spectrometer, for analyzing the separation. In one implementation, the liquid chromatography system10is a modified ACQUITY UPLC System the ACQUITY UPLC system available from Waters Corporation of Milford MA.

FIG.2depicts a perspective view of the column enclosure20, in accordance with one embodiment. The column enclosure20includes a column housing50. While not shown, the column enclosure20may further include an electronics housing coupled to the column housing. The electronics housing may be configured to control various features of the column enclosure20such as a column heater and/or a column pre-heater system80.

The column housing50further includes a front door52coupled to the column housing50along its length by a hinge. Opposite the hinge may be a mechanical latch (not shown) for closing the front door52of the column housing50. The column enclosure20may incorporate various features of known column enclosures, such as an electrical device used to read identification from chromatography columns. As another example, the front door52may incorporate a magnetic switch located at the hinge end to detect when a connection is broken (i.e. when the front door52opens). The column enclosure20may use signals from such a switch to determine whether to maintain or disconnect power to the active pre-heater assembly80installed within the column enclosure20.

The interior of the column housing50includes a trough54within which a chromatography column56is shown after having been fluidically connected into the column enclosure20. The trough54may be configured to receive and accommodate chromatography columns having different lengths and diameters.

The column housing50of the column enclosure20extends along a length between a column inlet end59and a column outlet end58. A clamp assembly60is located within the column housing50including both a rail62and a carriage64having a hand operated cam loaded lever65. The rail62extends along the length of the housing. In the embodiment shown, the rail62is in the form of a guide rod that extends parallel to the chromatography column56within the column housing50. A carriage64is shown movably attachable to the rail62such that the carriage64may move along the rail62, where the movement is confined to one dimension or axis by the attachment with the rail62. The underside of the carriage64includes a projection66that is keyed to a plurality of separate cavities68,70,72,74disposed along the length of the trough54. The bottom of the carriage64is dimensioned to fit snugly into each of the cavities68,70,72,74to retain the carriage64in a stable position during actuation of the carriage64to establish a fluidic connection. The carriage64further includes a bore76within which the rail62extends. As described in more detail hereinbelow, the carriage64is configured to be rotated about the rail62to move the carriage64into and out of the plurality of separate cavities68,70,72,74located at predetermined locations along the length of the rail62.

The various cavities68,70,72,74located along the trough54may be particularly dimensioned at lengths along the trough54to accommodate standardized chromatography column lengths and/or dimensions. For example, the cavity68is shown located at a length within the trough54to accommodate a 150 mm column. The cavity70is shown located at a length within the trough54to accommodate a 100 mm column. Likewise, the cavity68is shown located at a length within the trough54to accommodate a 50 mm column. Finally, the cavity74is shown located at a length within the trough54to accommodate a 30 mm column.

The carriage64also includes the lever65that is attached to the carriage. The lever65may be cam loaded, which, when the clamp assembly60is in an engaged condition, engage a first fluidic assembly (not shown) received or otherwise within the carriage64to control movement of the first fluidic assembly relative to the body or frame of the carriage64. In general, the clamp assembly60receives and retains the chromatography column56and establishes a fluid connection between a second fluidic assembly80, such as an outlet to a detector or mass spectrometer, and the chromatography column56, and between the first fluidic assembly found within the carriage64and the chromatography column56.

The first fluidic assembly may, for example, be a needle barrel assembly, as described in International Patent Application No. PCT/US12/68712, filed Dec. 10, 2012, the complete disclosure of which is incorporated herein by reference to the extent it is not inconsistent with the present disclosure. Alternatively, the first fluidic assembly may be any other form of assembly configured to create a seal with an end of the chromatography column56. While the carriage64is shown proximate the inlet end of the chromatography column56in the embodiment shown, the clamp assembly60may be configured for connecting a chromatography column56having a reversed orientation, as in International Patent Application No. PCT/US12/68712.

One of the fluidic assemblies may include an active preheater assembly, as described in International Patent Application No. PCT/US12/68712. The active pre-heater assembly may be fluidically connected to the sample manager14(FIG.2) by way of an inlet capillary tubing. It should be understood that the clamp assembly60may be configured to clamp the chromatography column56into any other type of fluidic assembly, sealing mechanism (such as a needle barrel assembly), or the like.

Referring now toFIGS.3A-3G, methods of connecting and disconnecting chromatography columns within the column enclosure20are shown.FIG.3Adepicts a top view of the column enclosure20ofFIG.2with the front door52closed in accordance with a first step of a method of changing a chromatography column, in accordance with one embodiment.

FIG.3Bdepicts a top view of the column enclosure20ofFIG.2with the front door opened54in accordance with a second step of a method of changing a chromatography column, in accordance with one embodiment. As shown, the chromatography column56is a 150 mm chromatography column. Here, the lever65of the carriage64is in an engaged position while the protrusion66of the carriage64rests within the cavity68, thereby holding the cavity68in place along the rail62. The first fluidic assembly within the carriage46is engaged with the end of the chromatography column56to create a fluid tight seal therewith.

FIG.3Cdepicts a top view of the column enclosure20ofFIG.2with the front door52opened in accordance with a third step of a method of changing a chromatography column, in accordance with one embodiment. Here, the lever65of the carriage64is in a released or disengaged position. Thus, the lever65of the clamp assembly60is displaceable between a disengaged position and the engaged position. The displacement of the lever65from the disengaged position to the engaged position displaces the first fluidic assembly, such as the above-described needle barrel assembly, such that, in the engaged position, the distal ends of the outlet needle protrude further outwardly from the carriage64toward the chromatography column56. Disengagement in this manner allows the carriage64to become detached from the chromatography column56in order to facilitate removal and/or replacement of the chromatography column56from the column enclosure20and the trough54thereof.

FIG.3Ddepicts a top view of the column enclosure20ofFIG.2with the front door52opened in accordance with a fourth step of a method of changing a chromatography column, in accordance with one embodiment. In this step, the fully disengaged carriage64has been rotated about the rail62. This frees the disengaged carriage64from engagement by the projection66into the cavity68and allows the carriage64to slide along the rail62. Further, this rotation about the rail62allows the carriage64to allow the chromatography column56to move along the trough54toward the second end59. This allows the chromatography column56to disengage from the seal with the active pre-heater assembly60.

FIG.3Edepicts a top view of the column enclosure20ofFIG.2with the front door52opened in accordance with a fifth step of a method of changing a chromatography column, in accordance with one embodiment. Here, the chromatography column56has been removed and replaced by a second chromatography column90. The second chromatography column90is a 30 mm column in length. As shown, the second column90is placed into the trough54in this step. The second column90is then slid towards the second fluidic assembly80.

FIG.3Fdepicts a top view of the column enclosure20ofFIG.3with the front door52opened in accordance with a sixth step of a method of changing a chromatography column, in accordance with one embodiment. In this step, the carriage64is slid towards the second chromatography column90until the carriage64is located at the 30 mm cavity74along the length of the rail62. Here, the carriage64may then be rotated about the rail62so that the projection65of the carriage64enters into the cavity74to retain the carriage64in position along the rail62. Once the carriage64is in this position, the carriage64may be positionally secured along the rail62and supported in a stable manner so that actuation can occur with sufficient leverage and the avoidance of movement of the carriage64along the length of the rail62.

FIG.3Gdepicts a top view of the column enclosure20ofFIG.3with the front door52opened in accordance with a seventh step of a method of changing a chromatography column, in accordance with one embodiment. Once the second chromatography column90and the carriage64are so positioned, the lever65is displaced from the disengaged position toward the engaged position. The lever65continues to rotate to cause the first fluidic assembly within the carriage64to transition toward the seal at the inlet end of the chromatography column90. Rotation of the lever65simultaneously, subsequently or additionally creates the seal between the second chromatography column90and the second fluidic assembly80at the outlet end of the second chromatography column90. That is, the rotation of the lever65into the engaged position also establishes the fluidic seal in the same or similar manner between the second chromatography column80and the active pre-heater assembly90.

The column enclosure20and clamp assembly60are capable of running at pressures of up to 20,000 pounds per square inch. This configuration can help to ensure repeatability of connection. This configuration can also help to ensure ease of connection, and helps to provide a fluid connection which does not require highly skilled operators to ensure that the connection is properly established. In addition, less mechanical force may be required to establish the fluid connections as compared to conventional threaded fittings or bayonet fittings which require application of torque, e.g., by hand alone or with the use of tools, to establish a fluid tight connection.

The column enclosure20and clamp assembly60has been described hereinabove with respect to a single embodiment. However, other embodiments are contemplated. Further, the clamp assembly60may be a separable component from the rest of the column enclosure20, rather than integral thereto. Such a clamp assembly may include a trough with one or more cavities, along with a rail for guiding the lengthwise movement of a cartridge having a lever, and may be utilized in other column enclosures20or other chromatography system column chambers with different configurations and arrangements than the embodiment shown.

FIG.4depicts a perspective view of another clamp assembly100for application within a column enclosure, such as the column enclosure20, with a lever110in a released position in accordance with another embodiment.FIG.5depicts another perspective view of the clamp assembly100ofFIG.4with the lever110in a load position, in accordance with one embodiment. The clamp assembly100herein includes a rail102extending along its length. The rail102may be configured to receive a first fluidic assembly104within a carriage106. The carriage106may be movably attachable to the rail102such that the carriage106moves along the rail102, the carriage106is configured to receive a second fluidic assembly108. The carriage106includes the lever110and a stop mechanism112.

The clamp assembly100may be configured with the same functionality and process for establishing fluidic seals at both ends of a chromatography column116as described hereinabove with respect to the clamp assembly60. However, the clamp assembly100has a different mechanism for moving lengthwise along the rail102, and for stopping lengthwise movement along the rail via the stop mechanism112. The rail102includes a dual rail structure where the stop mechanism112includes an assembly that extends across to both sides of the rail102. Further, the carriage106does not rotate about the rail102to engage with keyed cavities to provide for stability and prevent lengthwise movement. Instead the stop mechanism112of the clamp assembly100creates stability and prevents lengthwise movement via engagement of the stop mechanism112to a toothed track on each side of the dual rail structure, as described in more detail herein below. Further, the dual rail structure of the rail102further accommodates a sliding retainer clip114that includes a cylindrical opening within the clip dimensioned to receive the circumference of the chromatography column116. This sliding retainer clip114can be slid along the rail102to accommodate chromatography columns of different lengths. The clip114can also be removed with a coin or other flat plate or the like. Such removal of the retainer clip114can allow for very short column lengths where the support provided by the clip114is unnecessary.

As shown, the first fluidic assembly104is proximate an inlet port of the chromatography column116while the second fluidic assembly108is proximate an outlet port of the chromatography column116. Like the embodiment above, the second fluidic assembly108may include system for connecting to a solvent tubing107which extends to a fitting109. The solvent tubing107may be configured to provide post-column addition of solvents to the system, prior to detection. The second fluidic assembly108further includes an outlet port in parallel with the column that is connectable to a fluidic channel (not shown) which brings fluid from the column to a mass spectrometer (not shown). It should be understood that in such an arrangement, the post column additional solvent tubing107is an option and not required.

The inlet port includes an inlet heater118through which an inlet tube120provides fluid that has passed through the chromatography column116to the downstream portion of the fluidic system.

FIG.6depicts a side view of the clamp assembly100ofFIGS.4-5with the lever110in a released position, in accordance with one embodiment. In the released position the lever110is positioned upward and a space exists between the first fluidic assembly104and the outlet end of the chromatography column116. As shown, the lever110includes an arm124extending between a first pin122and a second pin126. Further, the rail102is shown including an array of teeth128extending along its length. While only one side of the dual rail structure is shown, the rail102includes an opposing side that includes the same structure as the side shown. As shown, an inlet fluidic tubing120enters the inlet heater118and exits the inlet heater118through tubing121. Tubing121transfers fluid into the first fluidic assembly104which is configured to be moved by actuation and/or rotation of the lever110.

The stop mechanism112is shown including a hand button130afor rotating a position retaining pawl132aabout a vertical pin136a. A frame134extends underneath between each side of the dual rail structure of the rail102. The frame134includes a C-shaped structure on each side (shown more clearly inFIGS.4-5). The C-shaped structure includes openings in the top and bottom, which receive vertical pin136a. The retaining pawl132ais configured to rotate about the vertical pin136a. The retaining pawl132aincludes the hand button130a. When the button130ais pressed, the respective pawl132arotates about the vertical pin136ato release engagement arm138a, having an array of locking teeth140afor engagement with the array of teeth128disposed along the rail102. When the button130a, is pressed, this allows the carriage106to slide along the rail102.

FIG.7depicts a side view of the clamp assembly100ofFIGS.4-6, in accordance with one embodiment. Unlike the state shown inFIG.6, the lever110inFIG.7has been rotated into a load position. Specifically, the lever110has been rotated counter-clockwise about the pin126. This rotating action may be accomplished by a technician by hand. Actuating the lever110brings the first fluidic assembly104into contact with the outlet end of the chromatography column116, thereby creating a fluid tight seal therewith.

FIG.8depicts a perspective view of an underside of the clamp assembly100ofFIGS.4-7with position retaining pawls132a,132bin a locked position, in accordance with one embodiment.FIG.9depicts a perspective view of an underside of the clamp assembly100ofFIGS.4-8with position retaining pawls132a,132bin a released position, in accordance with one embodiment. As shown, the retaining locking mechanism described hereinabove with respect to one side including the button130a, retaining pawl132a, vertical pin136a, release engagement arm138a, and locking teeth140ais also included on the other side. Specifically, the opposing side of the rail102includes a corresponding button130b, a retaining pawl132b, a vertical pin136a, a release engagement arm138a, and locking teeth140b.

The respective engagement arms138a,138beach include a respective vertical bolt154a,154bextending therethrough. A spring150extending between endrings152a,152bis located between the vertical bolts154a,154b. In particular, the endrings152a,152bof the spring150may each be inserted into the vertical bolts154a,154bprior to the vertical bolts154a,154bbeing inserted into threaded vertical openings of the engagement arms138a,138b, as shown inFIG.10.FIGS.8-9show one side of the spring150connected in this manner, but it should be understood that in operation of the clamp assembly100, both sides are connected. The spring150is configured to pull the array of locking teeth140a,140bof each of the engagement arms138a,138binto engagement with the array of teeth128of each side of the rail102. This may provide for selective movement or movement prevention of the carriage106along the rail102. To move the carriage106along the rail102, a technician may press the buttons130a,130bto expand the spring150and release the locking teeth140a,140bof the arms138a,138bfrom the array of teeth128of the rail102. Then, to stop movement of the carriage106along the rail102, a user would release the buttons130a,130bwhich causes the spring150to contract, thereby re-engaging the teeth140a,140bwith the teeth128of the rail102. This stop mechanism for preventing movement of the rail may be configured to act independently of the actuation of the lever110. Thus, the carriage106may be stopped from movement along the rail102before the lever110is actuated.

Further, as shown inFIGS.8-9, the sliding retainer clip114is held between the rail102through a clamp mechanism115that includes bolt extending through a flat thin plate extending on both sides of the bolt to each of the sides of the rail102. The plate may be spring loaded to maintain tension. The plate and bolt create the clamp115configured to selectively loosen and tighten the sliding retainer clip114to allow the retainer clip114to be positioned along the rail102in accordance with the size of the column is being accommodated by the clamp assembly100.

Referring now toFIG.10, another clamp assembly200is shown for application within a column enclosure, such as the column enclosure20, with a lever210in a released position in accordance with another embodiment. The clamp assembly200may be similar to the clamp assembly100described hereinabove. Similar to the clamp assembly100, the clamp assembly200includes the lever210configured to operably move a first fluidic assembly204into engagement with a chromatography column214and further to push the chromatography column214into a fluidic seal with the second fluidic assembly208. Like the embodiment above, the second fluidic assembly208may include system for connecting to a solvent tubing207which extends to a fitting209. The solvent tubing207may be configured to provide post-column addition of solvents to the system, prior to detection. The second fluidic assembly208further includes an outlet port in parallel with the column that is connectable to a fluidic channel (not shown) which brings fluid from the column to a mass spectrometer (not shown). It should be understood that in such an arrangement, the post column additional solvent tubing207is an option and not required.

Further, like the clamp assembly100, the clamp assembly200includes an inlet heater218through which an inlet tube220provides fluid that has passed through the chromatography column116to the downstream portion of the fluidic system. However, the clamp assembly200includes a track202and stop mechanism212for locking the carriage206to the track202that is different from the track102and lock mechanism112of the clamp assembly100.

FIG.11depicts a side view of the clamp assembly ofFIG.10with the clamp lever in a load position, in accordance with one embodiment. Specifically, the lever210has been rotated counter-clockwise about a pin226. This rotating action may be accomplished by a technician by hand. Actuating the lever210brings the first fluidic assembly204into contact with the outlet end of the chromatography column216, thereby creating a fluid tight seal between the first fluidic assembly204and the chromatography column216. Further, this rotation and actuation may simultaneously bring the chromatography column216into contact with the second fluidic assembly208, thereby creating a fluid tight seal between, the chromatography column216and the second fluidic assembly208.

FIG.12depicts a perspective view of an underside of the clamp assembly ofFIGS.10-11, in accordance with one embodiment. As shown, the clamp assembly200includes the stop mechanism212having a hand button230for rotating a position retaining pawl235about a horizontal pin236extending through both the position retaining pawl235and a U-shaped structure232of a frame234. The frame234extends underneath between each side of the dual rail structure of the rail202. The frame234includes the U-shaped structure232on each side through which the horizontal pin236extends and about which the retaining pawl235rotates. The U-shaped structure includes openings in the left and right side, which receive the horizontal pin236. The retaining pawl235is configured to rotate about the horizontal pin236in this manner. When the button230is pressed, the pawl235rotates about the vertical pin236to release an engagement arm (shown inFIG.13), having an array of locking teeth (shown inFIG.13) for engagement with the array of teeth disposed along the bottom of rail plate228. When the button130, is pressed, this allows the carriage206to slide along the rail202. While not shown in this view, it should be understood that the structure of the lock mechanism212is mirrored on the other side of the dual rail202. Thus, each of the hand button230, retaining pawl235, horizontal pin236, and u-shaped structure232are included on the opposite side of the rail202hidden from the view shown inFIG.12in the same configuration.

Further shown in this view is a clamp mechanism215, similar or the same as the clamp mechanism115, that includes bolt extending through a flat thin plate extending on both sides of the bolt to each of the sides of the rail202. The plate and bolt create the clamp215configured to selectively loosen and tighten the sliding retainer clip214to allow the retainer clip214to be positioned along the rail102in accordance with the size of the column is being accommodated by the clamp assembly200.

FIG.13depicts an enlarged view of a stop mechanism212of the clamp assembly100ofFIGS.10-11, in accordance with one embodiment. As shown, the stop mechanism212includes the retaining pawl235rotating about the horizontal pin236which extends through the structure of the frame234. The retaining pawl235extends to an engagement arm238having an array of locking teeth240upwardly disposed thereon. The locking teeth240are configured to engage with bottom teeth229aof the rail plate228. Top teeth229bof the rail plate228are configured to engage with a bottom surface205of the rail202. This bottom surface205may or may not have teeth to engage with the top teeth229b. The engagement arm238is shown including a cavity, bore or hallow for receiving a spring242. The spring242may be configured to put upward pressure on the engagement arm238in order to maintain locking of the upward facing locking teeth240of the engagement arm with the downward facing teeth229aof the rail plate228. The rail plate228may be a removable and replaceable component of the rail202, in the event that the teeth thereon become warn.

Thus, to disengage and remove the carriage206from the rail202, a technician would squeeze both buttons230of the stop mechanism212. This would rotate the pawl235about the pin236in a counterclockwise direction. The engagement arm238would then separate from the rail plate228. This disengages the carriage206from the rail202so that the carriage can be freely slid axially along the rail202while the buttons230are pressed. When the buttons230are released, the pawl235rotates clockwise about the pin236due to the spring force from the spring242, thereby re-engaging the engagement arm238with the rail plate228.

Although a few implementations and methods have been described in detail above, other modifications are possible. In certain implementations, fitting adapters can be provided for converting chromatography columns with conventional ferrule type fitting connections. Although a clamp assembly has been described for use in a column enclosure, in some implementations, the clamp assembly may alternatively or additionally be configured for use in a column manager, such as the ACQUITY UPLC® Column Manager available from Waters Corporation of Milford MA.

While the invention has been shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as recited in the accompanying claims.