Patent Description:
This disclosure relates to establishing fluidic connections between chromatography components. In particular, the disclosure relates to devices and methods for establishing a fluidic connection of a chromatography column into a chromatography and/or mass spectrometry system.

Chromatography is a set of techniques for separating a mixture into its constituents. Generally, in a liquid chromatography analysis, a pump system takes in and delivers a mixture of liquid solvents (and/or other fluids) to a sample manager, where a sample awaits injection into the solvents. The sample is the material under analysis. Examples of samples include complex mixtures of proteins, protein precursors, protein fragments, reaction products, and other compounds, to list but a few. In an isocratic chromatography application, the composition of the liquid solvents remains unchanged, whereas in a gradient chromatography application, the solvent composition varies over time. The mobile phase, comprised of a sample dissolved in a mixture of solvents (and/or other fluids), moves to a point of use, such as a column, which includes a packing material referred to as the stationary phase.

By passing the mobile phase through the column, the various components in the sample separate from each other at different rates and thus elute from the column at different times. A detector receives the separated components from the column and produces an output from which the identity and quantity of the analytes may be determined. Temperature can influence the results of the analysis, affecting such properties as the separation performance of the column and the viscosity of a mobile phase. Therefore, maintaining an accurate constant column temperature can be important to the accuracy and reproducibility of the results.

Systems used for performing chromatography analysis often include fluidic tubing for providing fluid communication between system components. For example, chromatography systems typically include components, such as pumps, valves, columns, and detectors, that are connected together through fluidic (e.g., metallic or polymeric) tubing. The system components and the fluidic tubing are often connected using threaded fittings or bayonet fittings. Connection and disconnection of these fittings (e.g., during assembly, repair, and/or replacement) can require application of torque, e.g., by hand alone or with the use of tools, to establish a fluid tight connection. This can be time consuming, cumbersome (e.g., in cases in which multiple turns are required), and may lead to leaks and/or failure if the fittings are not threaded together properly and/or if adequate torque is not applied when the connection is made.

In modem chromatography, systems pressures are being increased and internal fluid volumes are being reduced. As a result, the reliability and seal characteristics of conventional fittings are becoming problematic. As the pressure is raised and the system internal fluid volume is reduced the fitting dead volume and sensitivity to the assemblers skill become impediments to chromatographic quality. In this regard, establishing fluid tight connections with such conventional fittings can require the use of skilled labor employing since it is often the case that a high degree of precision is required to ensure the connection is not only fluid tight, but is also devoid of undesirable dead volume which can lead to lost precision in the measured data.

Establishing fluid tight connections with skilled labor typically requires the use of tools. These types of connections may be difficult to establish, even with the aid of tools. Even with tools and a skilled technician, it may be tedious to complete and easy to get wrong. In particular, the installation of a chromatography column into a chromatography and/or mass spectrometry system can lead to questions regarding proper positioning and orientation, as well as whether the installation was done properly. The present invention also seeks to improve existing known techniques for establishing these connections without the use of hand tools, such as the clamp assembly described in <CIT>, entitled "Establishing Fluidic Connections between Chromatography Components.

<CIT> discloses a holding device for chromatography columns. <CIT> discloses a separation column connection device, a connection method, and analysis system.

The present invention provides a column enclosure for a chromatography column comprising: a column housing extending along a length; a rail extending along the length within the column housing; a carriage movably attachable to the rail such that the carriage moves along the rail, the carriage including an actuator and a stop mechanism; a first fluidic assembly configured to be moved by the actuator into engagement with a chromatography column received within the column housing; and a second fluidic assembly located proximate an end of the rail; wherein the stop mechanism is configured to selectively prevent and allow movement of the carriage relative to the rail, wherein the stop mechanism is configured to be independently operable from the actuator, and wherein the actuator is configured: to establish a first fluid tight seal between the first fluidic assembly and the chromatography column; and to establish a second fluid tight seal between the second fluidic assembly and the chromatography column.

Additionally or alternatively, the stop mechanism includes a projection on the carriage keyed to a plurality of separate locations along the rail, each of the plurality of separate locations corresponding to standard lengths of chromatography columns.

The rail is a guide rod and wherein the carriage includes a bore through which the guide rod extends, wherein the carriage is configured to be rotated about the guide rod to move the carriage into and out of the plurality of separate locations along the rail.

Additionally or alternatively, the actuator is a hand operated cam loaded lever.

Additionally or alternatively, the rail includes a first plurality of teeth arranged along the length, and wherein the stop mechanism includes a first lock pawl that is configured to engage the teeth of the rail, thereby to inhibit movement of the carriage relative to the rail.

Additionally or alternatively, the rail includes a second plurality of teeth arranged along the length on an opposite side of the first plurality of teeth, and wherein the stop mechanism includes a second lock pawl on an opposite side of the carriage as the first lock pawl, wherein the first and second lock pawls are each configured to engage the teeth of the rail, thereby to inhibit movement of the carriage relative to the rail.

Additionally or alternatively, a spring extends between each of the first and second lock pawls to maintain locking of the stop mechanism.

Additionally or alternatively, the lock pawls are configured to be squeezed by hand to release to stop mechanism from the first and second plurality of teeth of the rail and thereby allow movement of the carriage with respect to the rail.

Additionally or alternatively, the column enclosure accommodates chromatography columns having at least one of various column lengths and various column diameters.

The present invention provides a clamp assembly comprising: a rail extending along the length and configured to receive a first fluidic assembly; and a carriage movably attachable to the rail such that the carriage moves along the rail, the carriage configured to receive a second fluidic assembly, the carriage including an actuator and a stop mechanism, where the stop mechanism is configured to selectively prevent and allow movement of the carriage relative to the rail, wherein the stop mechanism is configured to be independently operable from the actuator assembly, and wherein the actuator is configured: to move a chromatography column received by the clamp assembly relative to the rail to create a first fluid tight seal between the chromatography column and the first fluidic assembly, and move the second fluidic assembly relative to the carriage body to create a second fluid tight seal between the second fluidic assembly and the chromatography column.

Additionally or alternatively, the carriage accommodates chromatography columns having at least one of various column lengths and various column diameters.

The present invention provides a method of establishing fluid tight seals comprising: receiving a first chromatography column by a clamp assembly; moving a carriage along a rail of the clamp assembly into a first position that corresponds to a length of the first chromatography column, the carriage including an actuator and a stop mechanism; preventing movement, by the stop mechanism of the carriage, of the carriage relative to the rail at the first position; after the preventing movement, engaging the actuator of the carriage; by the engaging of the actuator, establishing a first fluid tight seal between the first fluidic assembly and the first chromatography column; and by the engaging of the actuator, establishing a second fluid tight seal between the second fluidic assembly and the first chromatography column.

Additionally or alternatively, the method further includes releasing the stop mechanism of the carriage; moving the carriage along the rail of the clamp assembly; removing the first chromatography column from the clamp assembly; receiving a second chromatography column by a clamp assembly; moving the carriage along the rail of the claim assembly to a second position that corresponds to a length of the second chromatography column; preventing movement, by the stop mechanism of the carriage, of the carriage relative to the rail at the second position; after the preventing movement, engaging the actuator of the carriage; by the engaging of the actuator, establishing a third fluid tight seal between the first fluidic assembly and the second chromatography column; and by the engaging of the actuator, establishing a fourth fluid tight seal between the second fluidic assembly and the second chromatography column.

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 <NUM> GPa, i.e. <NUM>,<NUM> 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> shows an implementation of a liquid chromatography system <NUM> for separating a sample into its constituents. The liquid chromatography system <NUM> includes a solvent delivery system <NUM> in fluidic communication with a sample manager <NUM>. Generally, the solvent delivery system <NUM> includes pumps (not shown) in fluidic communication with solvent reservoirs from which the pumps draw solvents. The solvent delivery system <NUM> delivers a mixture of solvents to the sample manager <NUM>. The sample manager <NUM> is in fluidic communication with a sample source <NUM> from which the sample manager acquires and introduces a sample to the solvent mixture arriving from the solvent delivery system <NUM>.

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

<FIG> depicts a perspective view of the column enclosure <NUM>, in accordance with one embodiment. The column enclosure <NUM> includes a column housing <NUM>. While not shown, the column enclosure <NUM> may further include an electronics housing coupled to the column housing. The electronics housing may be configured to control various features of the column enclosure <NUM> such as a column heater and/or a column pre-heater system <NUM>.

The column housing <NUM> further includes a front door <NUM> coupled to the column housing <NUM> along its length by a hinge. Opposite the hinge may be a mechanical latch (not shown) for closing the front door <NUM> of the column housing <NUM>. The column enclosure <NUM> may incorporate various features of known column enclosures, such as an electrical device used to read identification from chromatography columns. As another example, the front door <NUM> may incorporate a magnetic switch located at the hinge end to detect when a connection is broken (i.e. when the front door <NUM> opens). The column enclosure <NUM> may use signals from such a switch to determine whether to maintain or disconnect power to the active pre-heater assembly <NUM> installed within the column enclosure <NUM>.

The interior of the column housing <NUM> includes a trough <NUM> within which a chromatography column <NUM> is shown after having been fluidically connected into the column enclosure <NUM>. The trough <NUM> may be configured to receive and accommodate chromatography columns having different lengths and diameters.

The column housing <NUM> of the column enclosure <NUM> extends along a length between a column inlet end <NUM> and a column outlet end <NUM>. A clamp assembly <NUM> is located within the column housing <NUM> including both a rail <NUM> and a carriage <NUM> having a hand operated cam loaded lever <NUM>. The rail <NUM> extends along the length of the housing. In the embodiment shown, the rail <NUM> is in the form of a guide rod that extends parallel to the chromatography column <NUM> within the column housing <NUM>. A carriage <NUM> is shown movably attachable to the rail <NUM> such that the carriage <NUM> may move along the rail <NUM>, where the movement is confined to one dimension or axis by the attachment with the rail <NUM>. The underside of the carriage <NUM> includes a projection <NUM> that is keyed to a plurality of separate cavities <NUM>, <NUM>, <NUM>, <NUM> disposed along the length of the trough <NUM>. The bottom of the carriage <NUM> is dimensioned to fit snugly into each of the cavities <NUM>, <NUM>, <NUM>, <NUM> to retain the carriage <NUM> in a stable position during actuation of the carriage <NUM> to establish a fluidic connection. The carriage <NUM> further includes a bore <NUM> within which the rail <NUM> extends. As described in more detail hereinbelow, the carriage <NUM> is configured to be rotated about the rail <NUM> to move the carriage <NUM> into and out of the plurality of separate cavities <NUM>, <NUM>, <NUM>, <NUM> located at predetermined locations along the length of the rail <NUM>.

The various cavities <NUM>, <NUM>, <NUM>, <NUM> located along the trough <NUM> may be particularly dimensioned at lengths along the trough <NUM> to accommodate standardized chromatography column lengths and/or dimensions. For example, the cavity <NUM> is shown located at a length within the trough <NUM> to accommodate a <NUM> column. The cavity <NUM> is shown located at a length within the trough <NUM> to accommodate a <NUM> column. Likewise, the cavity <NUM> is shown located at a length within the trough <NUM> to accommodate a <NUM> column. Finally, the cavity <NUM> is shown located at a length within the trough <NUM> to accommodate a <NUM> column.

The carriage <NUM> also includes the lever <NUM> that is attached to the carriage. The lever <NUM> may be cam loaded, which, when the clamp assembly <NUM> is in an engaged condition, engage a first fluidic assembly (not shown) received or otherwise within the carriage <NUM> to control movement of the first fluidic assembly relative to the body or frame of the carriage <NUM>. In general, the clamp assembly <NUM> receives and retains the chromatography column <NUM> and establishes a fluid connection between a second fluidic assembly <NUM>, such as an outlet to a detector or mass spectrometer, and the chromatography column <NUM>, and between the first fluidic assembly found within the carriage <NUM> and the chromatography column <NUM>.

The first fluidic assembly may, for example, be a needle barrel assembly, as described in <CIT>. Alternatively, the first fluidic assembly may be any other form of assembly configured to create a seal with an end of the chromatography column <NUM>. While the carriage <NUM> is shown proximate the inlet end of the chromatography column <NUM> in the embodiment shown, the clamp assembly <NUM> may be configured for connecting a chromatography column <NUM> having a reversed orientation, as in <CIT>.

One of the fluidic assemblies may include an active preheater assembly, as described in <CIT>. The active pre-heater assembly may be fluidically connected to the sample manager <NUM> (<FIG>) by way of an inlet capillary tubing. It should be understood that the clamp assembly <NUM> may be configured to clamp the chromatography column <NUM> into any other type of fluidic assembly, sealing mechanism (such as a needle barrel assembly), or the like.

Referring now to <FIG>, methods of connecting and disconnecting chromatography columns within the column enclosure <NUM> are shown. <FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> closed in accordance with a first step of a method of changing a chromatography column, in accordance with one embodiment.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door opened <NUM> in accordance with a second step of a method of changing a chromatography column, in accordance with one embodiment. As shown, the chromatography column <NUM> is a <NUM> chromatography column. Here, the lever <NUM> of the carriage <NUM> is in an engaged position while the protrusion <NUM> of the carriage <NUM> rests within the cavity <NUM>, thereby holding the cavity <NUM> in place along the rail <NUM>. The first fluidic assembly within the carriage <NUM> is engaged with the end of the chromatography column <NUM> to create a fluid tight seal therewith.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> opened in accordance with a third step of a method of changing a chromatography column, in accordance with one embodiment. Here, the lever <NUM> of the carriage <NUM> is in a released or disengaged position. Thus, the lever <NUM> of the clamp assembly <NUM> is displaceable between a disengaged position and the engaged position. The displacement of the lever <NUM> from 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 carriage <NUM> toward the chromatography column <NUM>. Disengagement in this manner allows the carriage <NUM> to become detached from the chromatography column <NUM> in order to facilitate removal and/or replacement of the chromatography column <NUM> from the column enclosure <NUM> and the trough <NUM> thereof.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> opened 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 carriage <NUM> has been rotated about the rail <NUM>. This frees the disengaged carriage <NUM> from engagement by the projection <NUM> into the cavity <NUM> and allows the carriage <NUM> to slide along the rail <NUM>. Further, this rotation about the rail <NUM> allows the carriage <NUM> to allow the chromatography column <NUM> to move along the trough <NUM> toward the second end <NUM>. This allows the chromatography column <NUM> to disengage from the seal with the active pre-heater assembly <NUM>.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> opened in accordance with a fifth step of a method of changing a chromatography column, in accordance with one embodiment. Here, the chromatography column <NUM> has been removed and replaced by a second chromatography column <NUM>. The second chromatography column <NUM> is a <NUM> column in length. As shown, the second column <NUM> is placed into the trough <NUM> in this step. The second column <NUM> is then slid towards the second fluidic assembly <NUM>.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> opened in accordance with a sixth step of a method of changing a chromatography column, in accordance with one embodiment. In this step, the carriage <NUM> is slid towards the second chromatography column <NUM> until the carriage <NUM> is located at the <NUM> cavity <NUM> along the length of the rail <NUM>. Here, the carriage <NUM> may then be rotated about the rail <NUM> so that the projection <NUM> of the carriage <NUM> enters into the cavity <NUM> to retain the carriage <NUM> in position along the rail <NUM>. Once the carriage <NUM> is in this position, the carriage <NUM> may be positionally secured along the rail <NUM> and supported in a stable manner so that actuation can occur with sufficient leverage and the avoidance of movement of the carriage <NUM> along the length of the rail <NUM>.

<FIG> depicts a top view of the column enclosure <NUM> of <FIG> with the front door <NUM> opened in accordance with a seventh step of a method of changing a chromatography column, in accordance with one embodiment. Once the second chromatography column <NUM> and the carriage <NUM> are so positioned, the lever <NUM> is displaced from the disengaged position toward the engaged position. The lever <NUM> continues to rotate to cause the first fluidic assembly within the carriage <NUM> to transition toward the seal at the inlet end of the chromatography column <NUM>.

Rotation of the lever <NUM> simultaneously, subsequently or additionally creates the seal between the second chromatography column <NUM> and the second fluidic assembly <NUM> at the outlet end of the second chromatography column <NUM>. That is, the rotation of the lever <NUM> into the engaged position also establishes the fluidic seal in the same or similar manner between the second chromatography column <NUM> and the active pre-heater assembly <NUM>.

The column enclosure <NUM> and clamp assembly <NUM> are capable of running at pressures of up to <NUM> GPa, i.e. <NUM>,<NUM> 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 enclosure <NUM> and clamp assembly <NUM> has been described hereinabove with respect to a single embodiment. However, other embodiments are contemplated. Further, the clamp assembly <NUM> may be a separable component from the rest of the column enclosure <NUM>, 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 enclosures <NUM> or other chromatography system column chambers with different configurations and arrangements than the embodiment shown.

<FIG> depicts a perspective view of another clamp assembly <NUM> for application within a column enclosure, such as the column enclosure <NUM>, with a lever <NUM> in a released position in accordance with another embodiment. <FIG> depicts another perspective view of the clamp assembly <NUM> of <FIG> with the lever <NUM> in a load position, in accordance with one embodiment. The clamp assembly <NUM> herein includes a rail <NUM> extending along its length. The rail <NUM> may be configured to receive a first fluidic assembly <NUM> within a carriage <NUM>. The carriage <NUM> may be movably attachable to the rail <NUM> such that the carriage <NUM> moves along the rail <NUM>, the carriage <NUM> is configured to receive a second fluidic assembly <NUM>. The carriage <NUM> includes the lever <NUM> and a stop mechanism <NUM>.

The clamp assembly <NUM> may be configured with the same functionality and process for establishing fluidic seals at both ends of a chromatography column <NUM> as described hereinabove with respect to the clamp assembly <NUM>. However, the clamp assembly <NUM> has a different mechanism for moving lengthwise along the rail <NUM>, and for stopping lengthwise movement along the rail via the stop mechanism <NUM>. The rail <NUM> includes a dual rail structure where the stop mechanism <NUM> includes an assembly that extends across to both sides of the rail <NUM>. Further, the carriage <NUM> does not rotate about the rail <NUM> to engage with keyed cavities to provide for stability and prevent lengthwise movement. Instead the stop mechanism <NUM> of the clamp assembly <NUM> creates stability and prevents lengthwise movement via engagement of the stop mechanism <NUM> to 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 rail <NUM> further accommodates a sliding retainer clip <NUM> that includes a cylindrical opening within the clip dimensioned to receive the circumference of the chromatography column <NUM>. This sliding retainer clip <NUM> can be slid along the rail <NUM> to accommodate chromatography columns of different lengths. The clip <NUM> can also be removed with a coin or other flat plate or the like. Such removal of the retainer clip <NUM> can allow for very short column lengths where the support provided by the clip <NUM> is unnecessary.

As shown, the first fluidic assembly <NUM> is proximate an inlet port of the chromatography column <NUM> while the second fluidic assembly <NUM> is proximate an outlet port of the chromatography column <NUM>. Like the embodiment above, the second fluidic assembly <NUM> may include system for connecting to a solvent tubing <NUM> which extends to a fitting <NUM>. The solvent tubing <NUM> may be configured to provide post-column addition of solvents to the system, prior to detection. The second fluidic assembly <NUM> further 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 tubing <NUM> is an option and not required.

The inlet port includes an inlet heater <NUM> through which an inlet tube <NUM> provides fluid that has passed through the chromatography column <NUM> to the downstream portion of the fluidic system.

<FIG> depicts a side view of the clamp assembly <NUM> of <FIG> with the lever <NUM> in a released position, in accordance with one embodiment. In the released position the lever <NUM> is positioned upward and a space exists between the first fluidic assembly <NUM> and the outlet end of the chromatography column <NUM>. As shown, the lever <NUM> includes an arm <NUM> extending between a first pin <NUM> and a second pin <NUM>. Further, the rail <NUM> is shown including an array of teeth <NUM> extending along its length. While only one side of the dual rail structure is shown, the rail <NUM> includes an opposing side that includes the same structure as the side shown. As shown, an inlet fluidic tubing <NUM> enters the inlet heater <NUM> and exits the inlet heater <NUM> through tubing <NUM>. Tubing <NUM> transfers fluid into the first fluidic assembly <NUM> which is configured to be moved by actuation and/or rotation of the lever <NUM>.

The stop mechanism <NUM> is shown including a hand button 130a for rotating a position retaining pawl 132a about a vertical pin 136a. A frame <NUM> extends underneath between each side of the dual rail structure of the rail <NUM>. The frame <NUM> includes a C-shaped structure on each side (shown more clearly in <FIG>). The C-shaped structure includes openings in the top and bottom, which receive vertical pin 136a. The retaining pawl 132a is configured to rotate about the vertical pin 136a. The retaining pawl 132a includes the hand button 130a. When the button 130a is pressed, the respective pawl 132a rotates about the vertical pin 136a to release engagement arm 138a, having an array of locking teeth 140a for engagement with the array of teeth <NUM> disposed along the rail <NUM>. When the button 130a, is pressed, this allows the carriage <NUM> to slide along the rail <NUM>.

<FIG> depicts a side view of the clamp assembly <NUM> of <FIG>, in accordance with one embodiment. Unlike the state shown in <FIG>, the lever <NUM> in <FIG> has been rotated into a load position. Specifically, the lever <NUM> has been rotated counter-clockwise about the pin <NUM>. This rotating action may be accomplished by a technician by hand. Actuating the lever <NUM> brings the first fluidic assembly <NUM> into contact with the outlet end of the chromatography column <NUM>, thereby creating a fluid tight seal therewith.

<FIG> depicts a perspective view of an underside of the clamp assembly <NUM> of <FIG> with position retaining pawls 132a, 132b in a locked position, in accordance with one embodiment. <FIG> depicts a perspective view of an underside of the clamp assembly <NUM> of <FIG> with position retaining pawls 132a, 132b in a released position, in accordance with one embodiment. As shown, the retaining locking mechanism described hereinabove with respect to one side including the button 130a, retaining pawl 132a, vertical pin 136a, release engagement arm 138a, and locking teeth 140a is also included on the other side. Specifically, the opposing side of the rail <NUM> includes a corresponding button 130b, a retaining pawl 132b, a vertical pin 136a, a release engagement arm 138a, and locking teeth 140b.

The respective engagement arms 138a, 138b each include a respective vertical bolt 154a, 154b extending therethrough. A spring <NUM> extending between endrings 152a, 152b is located between the vertical bolts 154a, 154b. In particular, the endrings 152a, 152b of the spring <NUM> may each be inserted into the vertical bolts 154a, 154b prior to the vertical bolts 154a, 154b being inserted into threaded vertical openings of the engagement arms 138a, 138b, as shown in <FIG>. <FIG> show one side of the spring <NUM> connected in this manner, but it should be understood that in operation of the clamp assembly <NUM>, both sides are connected. The spring <NUM> is configured to pull the array of locking teeth 140a, 140b of each of the engagement arms 138a, 138b into engagement with the array of teeth <NUM> of each side of the rail <NUM>. This may provide for selective movement or movement prevention of the carriage <NUM> along the rail <NUM>. To move the carriage <NUM> along the rail <NUM>, a technician may press the buttons 130a, 130b to expand the spring <NUM> and release the locking teeth 140a, 140b of the arms 138a, 138b from the array of teeth <NUM> of the rail <NUM>. Then, to stop movement of the carriage <NUM> along the rail <NUM>, a user would release the buttons 130a, 130b which causes the spring <NUM> to contract, thereby re-engaging the teeth 140a, 140b with the teeth <NUM> of the rail <NUM>. This stop mechanism for preventing movement of the rail may be configured to act independently of the actuation of the lever <NUM>. Thus, the carriage <NUM> may be stopped from movement along the rail <NUM> before the lever <NUM> is actuated.

Further, as shown in <FIG>, the sliding retainer clip <NUM> is held between the rail <NUM> through a clamp mechanism <NUM> that includes bolt extending through a flat thin plate extending on both sides of the bolt to each of the sides of the rail <NUM>. The plate may be spring loaded to maintain tension. The plate and bolt create the clamp <NUM> configured to selectively loosen and tighten the sliding retainer clip <NUM> to allow the retainer clip <NUM> to be positioned along the rail <NUM> in accordance with the size of the column is being accommodated by the clamp assembly <NUM>.

Referring now to <FIG>, another clamp assembly <NUM> is shown for application within a column enclosure, such as the column enclosure <NUM>, with a lever <NUM> in a released position in accordance with another embodiment. The clamp assembly <NUM> may be similar to the clamp assembly <NUM> described hereinabove. Similar to the clamp assembly <NUM>, the clamp assembly <NUM> includes the lever <NUM> configured to operably move a first fluidic assembly <NUM> into engagement with a chromatography column <NUM> and further to push the chromatography column <NUM> into a fluidic seal with the second fluidic assembly <NUM>. Like the embodiment above, the second fluidic assembly <NUM> may include system for connecting to a solvent tubing <NUM> which extends to a fitting <NUM>. The solvent tubing <NUM> may be configured to provide post-column addition of solvents to the system, prior to detection. The second fluidic assembly <NUM> further 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 tubing <NUM> is an option and not required.

Further, like the clamp assembly <NUM>, the clamp assembly <NUM> includes an inlet heater <NUM> through which an inlet tube <NUM> provides fluid that has passed through the chromatography column <NUM> to the downstream portion of the fluidic system. However, the clamp assembly <NUM> includes a track <NUM> and stop mechanism <NUM> for locking the carriage <NUM> to the track <NUM> that is different from the track <NUM> and lock mechanism <NUM> of the clamp assembly <NUM>.

<FIG> depicts a side view of the clamp assembly of <FIG> with the clamp lever in a load position, in accordance with one embodiment. Specifically, the lever <NUM> has been rotated counter-clockwise about a pin <NUM>. This rotating action may be accomplished by a technician by hand. Actuating the lever <NUM> brings the first fluidic assembly <NUM> into contact with the outlet end of the chromatography column <NUM>, thereby creating a fluid tight seal between the first fluidic assembly <NUM> and the chromatography column <NUM>. Further, this rotation and actuation may simultaneously bring the chromatography column <NUM> into contact with the second fluidic assembly <NUM>, thereby creating a fluid tight seal between, the chromatography column <NUM> and the second fluidic assembly <NUM>.

<FIG> depicts a perspective view of an underside of the clamp assembly of <FIG>, in accordance with one embodiment. As shown, the clamp assembly <NUM> includes the stop mechanism <NUM> having a hand button <NUM> for rotating a position retaining pawl <NUM> about a horizontal pin <NUM> extending through both the position retaining pawl <NUM> and a U-shaped structure <NUM> of a frame <NUM>. The frame <NUM> extends underneath between each side of the dual rail structure of the rail <NUM>. The frame <NUM> includes the U-shaped structure <NUM> on each side through which the horizontal pin <NUM> extends and about which the retaining pawl <NUM> rotates. The U-shaped structure includes openings in the left and right side, which receive the horizontal pin <NUM>. The retaining pawl <NUM> is configured to rotate about the horizontal pin <NUM> in this manner. When the button <NUM> is pressed, the pawl <NUM> rotates about the vertical pin <NUM> to release an engagement arm (shown in <FIG>), having an array of locking teeth (shown in <FIG>) for engagement with the array of teeth disposed along the bottom of rail plate <NUM>. When the button <NUM>, is pressed, this allows the carriage <NUM> to slide along the rail <NUM>. While not shown in this view, it should be understood that the structure of the lock mechanism <NUM> is mirrored on the other side of the dual rail <NUM>. Thus, each of the hand button <NUM>, retaining pawl <NUM>, horizontal pin <NUM>, and u-shaped structure <NUM> are included on the opposite side of the rail <NUM> hidden from the view shown in <FIG> in the same configuration.

Further shown in this view is a clamp mechanism <NUM>, similar or the same as the clamp mechanism <NUM>, that includes bolt extending through a flat thin plate extending on both sides of the bolt to each of the sides of the rail <NUM>. The plate and bolt create the clamp <NUM> configured to selectively loosen and tighten the sliding retainer clip <NUM> to allow the retainer clip <NUM> to be positioned along the rail <NUM> in accordance with the size of the column is being accommodated by the clamp assembly <NUM>.

<FIG> depicts an enlarged view of a stop mechanism <NUM> of the clamp assembly <NUM> of <FIG>, in accordance with one embodiment. As shown, the stop mechanism <NUM> includes the retaining pawl <NUM> rotating about the horizontal pin <NUM> which extends through the structure of the frame <NUM>. The retaining pawl <NUM> extends to an engagement arm <NUM> having an array of locking teeth <NUM> upwardly disposed thereon. The locking teeth <NUM> are configured to engage with bottom teeth 229a of the rail plate <NUM>. Top teeth 229b of the rail plate <NUM> are configured to engage with a bottom surface <NUM> of the rail <NUM>. This bottom surface <NUM> may or may not have teeth to engage with the top teeth 229b. The engagement arm <NUM> is shown including a cavity, bore or hallow for receiving a spring <NUM>. The spring <NUM> may be configured to put upward pressure on the engagement arm <NUM> in order to maintain locking of the upward facing locking teeth <NUM> of the engagement arm with the downward facing teeth 229a of the rail plate <NUM>. The rail plate <NUM> may be a removable and replaceable component of the rail <NUM>, in the event that the teeth thereon become warn.

Thus, to disengage and remove the carriage <NUM> from the rail <NUM>, a technician would squeeze both buttons <NUM> of the stop mechanism <NUM>. This would rotate the pawl <NUM> about the pin <NUM> in a counterclockwise direction. The engagement arm <NUM> would then separate from the rail plate <NUM>. This disengages the carriage <NUM> from the rail <NUM> so that the carriage can be freely slid axially along the rail <NUM> while the buttons <NUM> are pressed. When the buttons <NUM> are released, the pawl <NUM> rotates clockwise about the pin <NUM> due to the spring force from the spring <NUM>, thereby re-engaging the engagement arm <NUM> with the rail plate <NUM>.

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.

Claim 1:
A clamp assembly (<NUM>) comprising:
a rail (<NUM>) extending along a length and configured to receive a first fluidic assembly (<NUM>, <NUM>); and
a carriage (<NUM>) movably attachable to the rail (<NUM>) such that the carriage (<NUM>) moves along the rail (<NUM>), the carriage (<NUM>) configured to receive a second fluidic assembly (<NUM>, <NUM>), the carriage (<NUM>) including an actuator (<NUM>) and a stop mechanism (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>),
where the stop mechanism (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>) is configured to selectively prevent and allow movement of the carriage (<NUM>) relative to the rail (<NUM>), wherein the stop mechanism (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>) is configured to be independently operable from the actuator (<NUM>), and wherein the actuator (<NUM>) is configured:
to move a chromatography column (<NUM>, <NUM>, <NUM>, <NUM>) received by the clamp assembly (<NUM>) relative to the rail (<NUM>) to create a first fluid tight seal between the chromatography column (<NUM>, <NUM>, <NUM>, <NUM>) and the first fluidic assembly (<NUM>, <NUM>), and
move the second fluidic assembly (<NUM>, <NUM>) relative to the carriage (<NUM>) to create a second fluid tight seal between the second fluidic assembly (<NUM>, <NUM>) and the chromatography column (<NUM>, <NUM>, <NUM>, <NUM>),
wherein the rail (<NUM>) is a guide rod and wherein the carriage (<NUM>) includes a bore (<NUM>) through which the guide rod extends, wherein the carriage (<NUM>) is configured to be rotated about the guide rod to move the carriage (<NUM>) into and out of a plurality of separate locations along the rail (<NUM>).