Establishing fluid connections between chromatographic components

Abstract

A clamping assembly includes a guide rail 62 extending along its length and configured to receive a first fluid assembly, and a bracket 64 movably attached to the guide rail 62 such that the bracket moves along the guide rail. The bracket 64 is configured to receive a second fluid assembly. The bracket includes an actuator 65 and a stop mechanism. The stop mechanism is configured to selectively prevent and allow movement of the bracket 64 relative to the guide rail 62. The stop mechanism is configured to operate independently of the actuator assembly, and the actuator is configured to: move a chromatographic column received by the clamping assembly relative to the guide rail to form a first impermeable fluid seal between the chromatographic column and the first fluid assembly, and move the second fluid assembly relative to the bracket body to form a second impermeable fluid seal between the second fluid assembly and the chromatographic column.

Description

[0001] Related applications

[0002] This patent application claims the benefit of an earlier filing date, U.S. Provisional Patent Application Serial No. 63 / 017,249, entitled “Establishing Fluidic Connections between Chromatography Components,” filed on April 29, 2020, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to establishing fluid connections between chromatographic components. Specifically, this disclosure relates to apparatus and methods for establishing fluid connections of chromatographic columns into chromatographic and / or mass spectrometry systems. Background Technology

[0004] Chromatography is a set of techniques for separating mixtures into their components. Generally, in liquid chromatography, a pump system receives and delivers a mixture of liquid solvent (and / or other fluids) to a sample manager, where the sample awaits infusion into the solvent. The sample is the material being analyzed. Examples of samples include complex mixtures of proteins, protein precursors, protein fragments, reaction products, and other compounds, to name just a few. In isocratic chromatography applications, the composition of the liquid solvent remains constant, while in gradient chromatography applications, the solvent composition changes over time. The mobile phase, consisting of the sample dissolved in the mixture of solvent (and / or other fluids), moves to the point of use, such as a column, which includes a packed material called the stationary phase.

[0005] 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. The detector receives the separated components from the column and generates an output from which the type and quantity of the analyte can be determined. Temperature can affect the analytical results, influencing the separation performance of the column and properties such as the viscosity of the mobile phase. Therefore, maintaining an accurate and constant column temperature is crucial for the accuracy and reproducibility of the results.

[0006] Systems used to perform chromatographic analysis typically include fluid tubing for providing fluid communication between system components. For example, a chromatographic system typically includes components such as pumps, valves, columns, and detectors connected together by fluid (e.g., metal or polymer) tubing. System components and fluid tubing are typically connected using threaded or bayonet fittings. Connecting and disconnecting these fittings (e.g., during assembly, repair, and / or replacement) may require applying torque, for example, manually or with tools, to establish a fluid-tight connection. This can be time-consuming and cumbersome (e.g., in cases requiring multiple turns), and can lead to leaks and / or malfunctions if the fittings are not properly threaded and / or if insufficient torque is applied during connection.

[0007] In modem chromatography, system pressure increases and the internal fluid volume decreases. Therefore, the reliability and sealing properties of conventional tubing become problematic. With increased pressure and reduced internal fluid volume, assembly dead volume and sensitivity to the skill of the installer become obstacles to chromatographic quality. In this regard, establishing impermeable connections with such conventional tubing may require skilled workers, as high precision is typically needed to ensure that the connection is not only impermeable but also free of undesirable dead volumes that could lead to loss of accuracy in the measurement data.

[0008] Establishing impermeable fluid connections typically requires the use of tools by skilled workers. Even with the aid of tools, these types of connections can be difficult to establish. Even with tools and skilled technicians, this can be challenging and error-prone. Specifically, installing a chromatographic column into a chromatographic and / or mass spectrometric system can lead to problems regarding proper positioning and orientation, and whether the installation was performed correctly. This invention also seeks to improve upon existing known techniques for establishing these connections without the use of manual tools, such as the clamp assembly described in U.S. Patent No. 10,338,038, entitled "Establishing Fluidic Connections between Chromatography Components". Summary of the Invention

[0009] According to one embodiment, a column housing for a chromatographic column includes: a column housing extending along its length; a guide rail extending along its length within the column housing; a bracket movably attached to the guide rail such that the bracket moves along the guide rail, the bracket including an actuator and a stop mechanism; a first fluid assembly configured by the actuator to engage with a chromatographic column received within the column housing; and a second fluid assembly located near an end of the guide rail; wherein the stop mechanism is configured to selectively prevent and allow movement of the bracket relative to the guide rail, wherein the stop mechanism is configured to operate independently of the actuator, and wherein the actuator is configured to: establish a first impermeable fluid seal between the first fluid assembly and the chromatographic column; and establish a second impermeable fluid seal between the second fluid assembly and the chromatographic column.

[0010] Alternatively or alternatively, the stop mechanism includes a protrusion located on the bracket that is engaged with a plurality of individual positions along the guide rail, each of which corresponds to a standard length of the chromatographic column.

[0011] Alternatively or alternatively, the guide rail is a guide rod, and the bracket includes a hole through which the guide rod extends, wherein the bracket is configured to rotate about the guide rod to move the bracket into and out of multiple individual positions along the guide rail.

[0012] Alternatively, the actuator is a manually operated cam-loaded lever.

[0013] Alternatively or alternatively, the guide rail includes a first plurality of teeth arranged along its length, and wherein the stop mechanism includes a first locking pawl configured to engage the teeth of the guide rail, thereby inhibiting movement of the bracket relative to the guide rail.

[0014] Alternatively or alternatively, the guide rail includes a second plurality of teeth arranged along its length on opposite sides of the first plurality of teeth, and wherein the stop mechanism includes a second locking pawl located on the opposite side of the bracket to the first locking pawl, wherein the first locking pawl and the second locking pawl are each configured to engage the teeth of the guide rail, thereby inhibiting movement of the bracket relative to the guide rail.

[0015] Alternatively or alternatively, the spring extends between each of the first and second locking pawls to maintain the locking of the stop mechanism.

[0016] Alternatively or alternatively, the locking pawl is configured to be manually squeezed to release from the first and second teeth of the guide rail to the stop mechanism, thereby allowing movement of the bracket relative to the guide rail.

[0017] Alternatively or alternatively, the column housing may accommodate a chromatographic column having at least one of a variety of column lengths and a variety of column diameters.

[0018] According to another embodiment, a clamp assembly includes: a guide rail extending along its length and configured to receive a first fluid assembly; and a bracket movably attached to the guide rail such that the bracket moves along the guide rail, the bracket being configured to receive a second fluid assembly, the bracket including an actuator and a stop mechanism, wherein the stop mechanism is configured to selectively prevent and allow movement of the bracket relative to the guide rail, wherein the stop mechanism is configured to operate independently of the actuator assembly, and wherein the actuator is configured to move a chromatographic column received by the clamp assembly relative to the guide rail to form a first impermeable fluid seal between the chromatographic column and the first fluid assembly, and to move the second fluid assembly relative to the bracket body to form a second impermeable fluid seal between the second fluid assembly and the chromatographic column.

[0019] Alternatively or alternatively, the stop mechanism includes a protrusion located on the bracket that is engaged with a plurality of individual positions along the guide rail, each of which corresponds to a standard length of the chromatographic column.

[0020] Alternatively or alternatively, the guide rail is a guide rod, and the bracket includes a hole through which the guide rod extends, wherein the bracket is configured to rotate about the guide rod to move the bracket into and out of multiple individual positions along the guide rail.

[0021] Alternatively, the actuator is a manually operated cam-loaded lever.

[0022] Alternatively or alternatively, the guide rail includes a first plurality of teeth arranged along its length, and wherein the stop mechanism includes a first locking pawl configured to engage the teeth of the guide rail, thereby inhibiting movement of the bracket relative to the guide rail.

[0023] Alternatively or alternatively, the guide rail includes a second plurality of teeth arranged along its length on opposite sides of the first plurality of teeth, and wherein the stop mechanism includes a second locking pawl located on the opposite side of the bracket to the first locking pawl, wherein the first locking pawl and the second locking pawl are each configured to engage the teeth of the guide rail, thereby inhibiting movement of the bracket relative to the guide rail.

[0024] Alternatively or alternatively, the spring extends between each of the first and second locking pawls to maintain the locking of the stop mechanism.

[0025] Alternatively or alternatively, the locking pawl is configured to be manually squeezed to release from the first and second teeth of the guide rail to the stop mechanism, thereby allowing movement of the bracket relative to the guide rail.

[0026] Alternatively or alternatively, the holder may accommodate a chromatographic column having at least one of a variety of column lengths and a variety of column diameters.

[0027] According to another embodiment, a method for establishing an impermeable fluid seal includes: receiving a first chromatographic column via a clamp assembly; moving a bracket along a guide rail of the clamp assembly to a first position corresponding to the length of the first chromatographic column, the bracket including an actuator and a stop mechanism; preventing movement of the bracket relative to the guide rail at the first position by the stop mechanism of the bracket; engaging the actuator of the bracket after preventing movement; establishing a first impermeable fluid seal between a first fluid assembly and the first chromatographic column by engaging the actuator; and establishing a second impermeable fluid seal between a second fluid assembly and the first chromatographic column by engaging the actuator.

[0028] Alternatively or concurrently, the method further includes: releasing a stop mechanism for the bracket; moving the bracket along a guide rail of the clamp assembly; removing the first chromatographic column from the clamp assembly; receiving the second chromatographic column through the clamp assembly; moving the bracket along the guide rail of the clamp assembly to a second position corresponding to the length of the second chromatographic column; preventing movement of the bracket relative to the guide rail at the second position by the stop mechanism of the bracket; engaging an actuator of the bracket after preventing movement; establishing a third impermeable fluid seal between the first fluid assembly and the second chromatographic column by engaging the actuator; and establishing a fourth impermeable fluid seal between the second fluid assembly and the second chromatographic column by engaging the actuator. Attached Figure Description

[0029] Figure 1 A functional block diagram of a liquid chromatography system including a column heater housing with a column housing, according to one embodiment, is depicted.

[0030] Figure 2 A perspective view of the column housing with the front door open according to one embodiment is depicted.

[0031] Figure 3A Figure 3 depicts a top view of the column housing, showing the first step of closing the front door according to an embodiment of a method for altering a chromatographic column.

[0032] Figure 3B Figure 3 depicts a top view of the column housing, showing the second step of a method for changing the chromatographic column according to one embodiment, with the front door opened.

[0033] Figure 3C Figure 3 depicts a top view of the column housing, showing the opening of the front door in the third step of a method for changing the chromatographic column according to one embodiment.

[0034] Figure 3D Figure 3 depicts a top view of the column housing, showing the opening of the front door in the fourth step of a method for changing the chromatographic column according to one embodiment.

[0035] Figure 3EFigure 3 depicts a top view of the column housing, showing the fifth step of a method for changing a chromatographic column according to one embodiment, with the front door opened.

[0036] Figure 3F Figure 3 depicts a top view of the column housing, showing the sixth step of a method for changing a chromatographic column according to one embodiment, with the front door opened.

[0037] Figure 3G Figure 3 depicts a top view of the column housing, showing the opening of the front door in the seventh step of a method for changing the chromatographic column according to one embodiment.

[0038] Figure 4 A perspective view of another clamping assembly for application within a column housing, according to another embodiment, is depicted, with the clamping rod in the released position.

[0039] Figure 5 Depicting according to an implementation scheme Figure 4 Another perspective view of the clamping assembly, with the clamping rod in the loading position.

[0040] Figure 6 Depicting according to an implementation scheme Figures 4 to 5 A side view of the clamp assembly, with the clamp lever in the released position.

[0041] Figure 7 Depicting according to an implementation scheme Figures 4 to 6 A side view of the clamping assembly, with the clamping rod in the loaded position.

[0042] Figure 8 Depicting according to an implementation scheme Figures 4 to 7 A perspective view of the lower side of the clamping assembly, where the position-holding pawl is in the locked position.

[0043] Figure 9 Depicting according to an implementation scheme Figures 4 to 8 A perspective view of the lower side of the clamping assembly, where the position holding pawl is in the released position.

[0044] Figure 10 A perspective view of another clamping assembly for application within a column housing, according to another embodiment, is depicted, with the clamping rod in the released position.

[0045] Figure 11 Depicting according to an implementation scheme Figure 10 A side view of the clamping assembly, with the clamping rod in the loaded position.

[0046] Figure 12 Depicting according to an implementation scheme Figures 10 to 11 A perspective view of the lower side of the clamping assembly.

[0047] Figure 13 Depicting according to an implementation scheme Figures 10 to 11 Enlarged view of the stop mechanism of the clamp assembly. Detailed Implementation

[0048] In this specification, references to "an embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of this teaching. References to a particular embodiment within this specification do not necessarily refer to the same embodiment.

[0049] The teachings will now be described in more detail with reference to exemplary embodiments illustrated in the accompanying drawings. While the teachings have been described in conjunction with various embodiments and examples, they are not intended to be limited to such embodiments. In contrast, the teachings encompass various alternatives, modifications, and equivalents, as will be understood by those skilled in the art. Those of ordinary skill in using the teachings herein will recognize additional implementations, modifications, and embodiments, as well as other areas of use, within the scope of this disclosure as set forth herein.

[0050] This disclosure arises from the understanding that a device can be provided to connect a chromatographic column without the use of hand tools (e.g., wrenches) or sleeves to suppress (e.g., prevent) transfer, dispersion, or dead volume. In some cases, impermeable fluid connections that do not require the application of torque (e.g., up to at least 20,000 psi) are provided, such as conventional fluid fittings typically with threaded or bayonet connections, and / or connections that can be made quickly and highly repeatable, requiring no highly skilled operator to ensure the connection is established correctly. Furthermore, it has been found that such a device should be able to accommodate chromatographic columns of different sizes, thus requiring the movement of a support bracket component for such accommodation. This disclosure further arises from the understanding that such a bracket requires significant stability prior to actuation of the connection to the chromatographic column.

[0051] The systems described herein include apparatus for connecting a fluid tube to a chromatographic column to establish an impermeable fluid connection therebetween. This apparatus provides a rapid and highly reproducible impermeable fluid connection that does not require a highly skilled operator to ensure the connection is established correctly. The apparatus allows column connection without the use of tools or tubing, thereby suppressing transfer, dispersion, or dead volume. Various embodiments of these systems relate to liquid chromatography apparatus coupled to mass spectrometry detection systems, such as HPLC (High Performance Liquid Chromatography) and UPLC (Ultra-High Performance Liquid Chromatography) systems. Furthermore, the apparatus includes a bracket with a connection actuator separate from the bracket movement stop mechanism. This allows the bracket to remain stable and establish a fluid connection with the chromatographic column before activating the connection actuator.

[0052] Figure 1An embodiment of a liquid chromatography system 10 for separating a sample into its components is shown. The liquid chromatography system 10 includes a solvent delivery system 12 in fluid communication with a sample manager 14. Generally, the solvent delivery system 12 includes a pump (not shown) in fluid communication with a solvent reservoir, which draws solvent from the reservoir. The solvent delivery system 12 delivers a solvent mixture to the sample manager 14. The sample manager 14 is in fluid communication with a sample source 18, from which the sample manager acquires the sample and introduces it into the solvent mixture arriving from the solvent delivery system 12.

[0053] Fluidly in communication with the sample manager 14 is the column housing 20, which provides a controlled temperature environment for the chromatographic column used to separate sample-solvent compositions. As described herein, the column housing 20 includes a fluid coupling device for establishing fluid connections between chromatographic components, e.g., between a fluid tube and the column. Components of the separated sample are transferred from the column housing 20 to the detector 16 or other devices (e.g., a mass spectrometer) for analysis of the separation. In one embodiment, the liquid chromatography system 10 is a modified ACQUITY UPLC system, available from Waters Corporation of Milford MA.

[0054] Figure 2 A perspective view of a column housing 20 according to one embodiment is depicted. The column housing 20 includes a column housing 50. Although not shown, the column housing 20 may also include an electronic housing coupled to the column housing. The electronic housing may be configured to control various features of the column housing 20, such as a column heater and / or a column preheater system 80.

[0055] The column housing 50 also includes a front door 52 connected to its length via a hinge. Opposite to the hinge may be a mechanical latch (not shown) for closing the front door 52 of the column housing 50. The column housing 20 may include various features known for column housings, such as electrical devices for reading identifiers from the chromatographic column. As another example, the front door 52 may include a magnetic switch located at the hinge end to detect when the connection is broken (i.e., when the front door 52 is open). The column housing 20 may use a signal from such a switch to determine whether to maintain or disconnect power to the active preheater assembly 80 mounted within the column housing 20.

[0056] The interior of the column housing 50 includes a groove 54 within which a chromatographic column 56, fluidly connected to the column housing 20, is displayed. The groove 54 can be configured to receive and accommodate chromatographic columns of different lengths and diameters.

[0057] The column housing 50 of the column housing 20 extends along the length between the column inlet end 59 and the column outlet end 58. A clamping assembly 60, located within the column housing 50, includes both a guide rail 62 and a bracket 64 with a manually operated cam loading rod 65. The guide rail 62 extends along the length of the housing. In the illustrated embodiment, the guide rail 62 is in the form of a guide rod extending parallel to the chromatographic column 56 within the column housing 50. The bracket 64 is shown movably attached to the guide rail 62, allowing the bracket 64 to move along the guide rail 62, wherein this movement is restricted in one dimension or axis by the attachment to the guide rail 62. The underside of the bracket 64 includes a protrusion 66 that is inserted into a plurality of individual chambers 68, 70, 72, 74 disposed along the length of a groove 54. The bottom of the bracket 64 is dimensioned to fit snugly into each of the chambers 68, 70, 72, 74 to hold the bracket 64 in a stable position to establish fluid connection during actuation. The bracket 64 also includes an aperture 76 in which a guide rail 62 extends. As described in more detail below, the bracket 64 is configured to rotate about the guide rail 62 to move the bracket 64 into and out of the plurality of individual chambers 68, 70, 72, 74 located at predetermined positions along the length of the guide rail 62.

[0058] The multiple chambers 68, 70, 72, and 74 positioned along groove 54 can be specifically sized along the length of groove 54 to accommodate standardized column lengths and / or dimensions. For example, chamber 68 is shown as having a length within groove 54 to accommodate a 150 mm column. Chamber 70 is shown as having a length within groove 54 to accommodate a 100 mm column. Similarly, chamber 68 is shown as having a length within groove 54 to accommodate a 50 mm column. Finally, chamber 74 is shown as having a length within groove 54 to accommodate a 30 mm column.

[0059] The bracket 64 also includes a rod 65 attached to the bracket. The rod 65 may be cam-loaded, and when the clamp assembly 60 is engaged, the rod engages to receive a first fluid assembly (not shown) that is present in or otherwise within the bracket 64 to control movement of the first fluid assembly relative to the body or frame of the bracket 64. Typically, the clamp assembly 60 receives and holds the column 56 and establishes fluid connections between a second fluid assembly (such as an outlet to a detector or mass spectrometer) and the column 56, as well as between the first fluid assembly found in the bracket 64 and the column 56.

[0060] For example, the first fluid assembly may be a syringe assembly, as described in International Patent Application No. PCT / US12 / 68712, filed December 10, 2012, the entire disclosure of which is incorporated herein by reference unless otherwise specified. Alternatively, the first fluid assembly may be any other form of assembly configured to form a seal with the end of the column 56. Although in the illustrated embodiment, the bracket 64 is shown near the inlet end of the column 56, the clamp assembly 60 may be configured for connecting the column 56 with reverse orientation, as described in International Patent Application No. PCT / US12 / 68712.

[0061] One of the fluid components may include an active preheater assembly, as described in International Patent Application No. PCT / US12 / 68712. The active preheater assembly may be fluidly connected to the sample manager 14 via an inlet capillary tube. Figure 2 It should be understood that the clamping assembly 60 can be configured to clamp the chromatographic column 56 into any other type of fluid assembly, sealing mechanism (such as a syringe assembly), etc.

[0062] Now for reference Figures 3A to 3G This illustrates a method for connecting and disconnecting the chromatographic column within the column housing 20. Figure 3A The first step of closing the front door 52 according to a method for changing the chromatographic column, as described in one embodiment, is depicted. Figure 2 Top view of the column shell 20.

[0063] Figure 3B The second step of opening the front door 52 according to a method of changing the chromatographic column, as described in one embodiment, is depicted. Figure 2 A top view of the column housing 20. As shown, the column 56 is a 150 mm column. Here, the rod 65 of the bracket 64 is in the engaged position, and the protrusion 66 of the bracket 64 rests within the chamber 68, thereby holding the chamber 68 in place along the guide rail 62. A first fluid assembly within the bracket 46 engages with the end of the column 56 to form a fluid-tight seal therewith.

[0064] Figure 3C The third step of a method for changing the chromatographic column, according to one embodiment, is described to open the front door 52. Figure 2A top view of the column housing 20. Here, the lever 65 of the holder 64 is in the released or disengaged position. Therefore, the lever 65 of the clamp assembly 60 can be displaced between the disengaged position and the engaged position. Displacement of the lever 65 from the disengaged position to the engaged position displaces the first fluid assembly (such as the syringe assembly described above) such that, in the engaged position, the distal end of the outlet needle protrudes further outward from the holder 64 toward the column 56. Disengagement in this manner allows the holder 64 to separate from the column 56, facilitating removal and / or replacement of the column 56 from the column housing 20 and its groove 54.

[0065] Figure 3D The method of changing the chromatographic column according to one embodiment is described in the fourth step of opening the front door 52. Figure 2 A top view of the column housing 20. In this step, the fully disengaged bracket 64 has been rotated about the guide rail 62. This releases the disengaged bracket 64 from engagement via the protrusion 66 entering the chamber 68 and allows the bracket 64 to slide along the guide rail 62. Furthermore, this rotation about the guide rail 62 allows the bracket 64 to allow the column 56 to move along the groove 54 toward the second end 59. This allows the column 56 to disengage from the active preheater assembly 80.

[0066] Figure 3E The fifth step of a method for changing the chromatographic column, according to one embodiment, is described to open the front door 52. Figure 2 A top view of the column housing 20. Here, the chromatographic column 56 has been removed and replaced by a second chromatographic column 90. The second chromatographic column 90 is a column with a length of 30 mm. As shown, in this step, the second column 90 is placed into the groove 54. The second column 90 is then slid toward the second fluid assembly.

[0067] Figure 3F Figure 3 depicts a top view of the column housing 20 of a method for altering a chromatographic column, showing the sixth step of opening the front door 52 according to one embodiment. In this step, the bracket 64 slides toward the second chromatographic column 90 until it is positioned in a chamber 74 30 mm along the length of the guide rail 62. Here, the bracket 64 can then be rotated about the guide rail 62 such that a protrusion 66 of the bracket 64 enters the chamber 74 to hold the bracket 64 in place along the guide rail 62. Once the bracket 64 is in this position, it is positioned and held stably along the guide rail 62, allowing sufficient leverage for actuation and preventing movement of the bracket 64 along the length of the guide rail 62.

[0068] Figure 3GFigure 3 depicts a top view of the column housing 20, showing the seventh step of a method for altering the column according to one embodiment, with the front door 52 opened. Once the second column 90 and the holder 64 are thus positioned, the lever 65 moves from the disengaged position toward the engaged position. The lever 65 continues to rotate to turn the first fluid assembly within the holder 64 toward the seal at the inlet end of the second column 90.

[0069] The rotation of rod 65 simultaneously, subsequently, or additionally creates a seal between the second column 90 and the second fluid assembly at the outlet end of the second column 90. That is, the rotation of rod 65 into the engagement position also establishes a fluid seal between the second column 90 and the active preheater assembly 80 in the same or similar manner.

[0070] The column housing 20 and clamp assembly 60 are capable of operating at pressures up to 20,000 psi. This configuration helps ensure the repeatability of the connection. It also helps ensure ease of connection and facilitates providing fluid connections without requiring highly skilled operators to ensure the connection is properly established. Furthermore, less mechanical force is required to establish a fluid connection compared to conventional threaded or bayonet fittings that require torque to establish a fluid-impermeable connection manually or with tools.

[0071] The column housing 20 and clamp assembly 60 have been described above with respect to a single embodiment. However, other embodiments are considered. Furthermore, the clamp assembly 60 may be a separable component from the rest of the column housing 20, rather than being integral with it. Such a clamp assembly may include a groove having one or more chambers, and a guide rail for guiding longitudinal movement of a bracket with a rod, and may be used in other column housings 20 or other chromatographic system column chambers having a configuration and arrangement different from the illustrated embodiment.

[0072] Figure 4 A perspective view of another clamping assembly 100 for application within a column housing, such as column housing 20, according to another embodiment is depicted, wherein the lever 110 is in the released position. Figure 5 Depicting according to an implementation scheme Figure 4 Another perspective view of the clamp assembly 100, with lever 110 in the loaded position. The clamp assembly 100 includes a guide rail 102 extending along its length. The guide rail 102 can be configured to receive a first fluid assembly 104 within a bracket 106. The bracket 106 can be movably attached to the guide rail 102 such that the bracket 106 moves along the guide rail 102, and the bracket 106 is configured to receive a second fluid assembly 108. The bracket 106 includes lever 110 and a stop mechanism 112.

[0073] The clamp assembly 100 can be configured to have the same function or process as described above with respect to clamp assembly 60 for establishing a fluid seal at both ends of the chromatographic column 116. However, the clamp assembly 100 has different mechanisms for longitudinal movement along the guide rail 102 and for stopping longitudinal movement along the guide rail via a stop mechanism 112. The guide rail 102 includes a double-rail structure, wherein the stop mechanism 112 includes components extending through both sides of the guide rail 102. Furthermore, the bracket 106 does not rotate about the guide rail 102 to engage with the keyed chamber to provide stability and prevent longitudinal movement. Instead, the stop mechanism 112 of the clamp assembly 100 provides stability and prevents longitudinal movement by engaging the stop mechanism 112 with toothed rails on each side of the double-rail structure, as described in more detail below. In addition, the double-rail structure of the guide rail 102 further accommodates a sliding retaining clip 114, which includes a cylindrical opening located within a clip sized to receive the circumference of the chromatographic column 116. The sliding retaining clip 114 can slide along the guide rail 102 to accommodate chromatographic columns of different lengths. The clip 114 can also be removed with a coin or other flat plate, etc. This removal of the retaining clip 114 allows for very short column lengths where the support provided by the clip 114 is unnecessary.

[0074] As shown in the figure, the first fluid assembly 104 is located near the inlet port of the chromatographic column 116, while the second fluid assembly 108 is located near the outlet port of the chromatographic column 116. Similar to the embodiment described above, the second fluid assembly 108 may include a system for connecting to a solvent tube 107, which extends to fitting 109. The solvent tube 107 may be configured as a post-column attachment to provide solvent to the system prior to detection. The second fluid assembly 108 also includes an outlet port in parallel with the column, which may be connected to a fluid channel (not shown) that carries fluid from the column to the mass spectrometer (not shown). It should be understood that in this arrangement, the post-column attached solvent tube 107 is an option, not a necessity.

[0075] The inlet port includes an inlet heater 118, through which the inlet pipe 120 supplies the fluid that has passed through the chromatographic column 116 to the downstream part of the fluid system.

[0076] Figure 6 Depicting according to an implementation scheme Figures 4 to 5A side view of the clamp assembly 100, with the lever 110 in the released position. In the released position, the lever 110 is positioned upwards and has space between the first fluid assembly 104 and the outlet end of the column 116. As shown, the lever 110 includes an arm 124 extending between a first pin 122 and a second pin 126. Furthermore, the guide rail 102 is shown as including an array of teeth 128 extending along its length. Although only one side of the dual guide rail structure is shown, the guide rail 102 includes an opposite side that includes the same structure as the shown side. As shown, the inlet fluid tube 120 enters the inlet heater 118 and exits the inlet heater 118 through a tube 121. The tube 121 transfers fluid to the first fluid assembly 104, which is configured to move by actuation and / or rotation of the lever 110.

[0077] The stop mechanism 112 is shown as including a manual button 130a for rotating a position-holding pawl 132a about a vertical pin 136a. A frame 134 extends lower between each side of the double-rail structure of the guide rail 102. The frame 134 includes a C-shaped structure on each side (in... Figures 4 to 5 (Seen more clearly in the image). The C-shaped structure includes openings in the top and bottom that receive a vertical pin 136a. A retaining pawl 132a is configured to rotate about the vertical pin 136a. The retaining pawl 132a includes a manual button 130a. When the button 130a is pressed, the corresponding pawl 132a rotates about the vertical pin 136a to release an engagement arm 138a having an array of locking teeth 140a to engage with an array of teeth 128 arranged along the guide rail 102. When the button 130a is pressed, this allows the bracket 106 to slide along the guide rail 102.

[0078] Figure 7 Depicting according to an implementation scheme Figures 4 to 6 Side view of the clamp assembly 100. (And) Figure 6 The states shown are different. Figure 7 The lever 110 has been rotated to the loading position. Specifically, the lever 110 rotates counterclockwise about the pin 126. This rotation can be performed manually by a technician. The actuating lever 110 brings the first fluid assembly 104 into contact with the outlet end of the chromatographic column 116, thereby forming an impermeable fluid seal therebetween.

[0079] Figure 8 Depicting according to an implementation scheme Figures 4 to 7 A perspective view of the lower side of the clamp assembly 100, wherein the position holding pawls 132a, 132b are in the locked position. Figure 9 Depicting according to an implementation scheme Figures 4 to 8The figure shows a perspective view of the lower side of the clamp assembly 100, with the position-holding pawls 132a and 132b in the released position. As shown, the retaining locking mechanism described above regarding one side, including the button 130a, retaining pawl 132a, pin 136a, release engagement arm 138a, and locking tooth 140a, is also included on the other side. Specifically, the opposite side of the guide rail 102 includes the corresponding button 130b, retaining pawl 132b, pin 136a, release engagement arm 138a, and locking tooth 140b.

[0080] The respective connecting arms 138a and 138b each include corresponding vertical bolts 154a and 154b extending therethrough. A spring 150 extending between end rings 152a and 152b is located between the vertical bolts 154a and 154b. Specifically, the end rings 152a and 152b of the spring 150 can each be inserted into the vertical bolts 154a and 154b before the vertical bolts 154a and 154b are inserted into the threaded vertical openings of the connecting arms 138a and 138b, as shown below. Figure 10 As shown. Figures 8 to 9 One side of the spring 150 connected in this manner is shown, but it should be understood that both sides are connected during operation of the clamp assembly 100. The spring 150 is configured to pull the array of locking teeth 140a, 140b of each of the engaging arms 138a, 138b into engagement with the array of teeth 128 on each side of the guide rail 102. This provides selective movement or movement prevention of the bracket 106 along the guide rail 102. To move the bracket 106 along the guide rail 102, a technician can press buttons 130a, 130b to expand the spring 150 and release the locking teeth 140a, 140b of the arms 138a, 138b from the array of teeth 128 on the guide rail 102. Then, to stop the movement of the bracket 106 along the guide rail 102, the user will release buttons 130a, 130b, which causes the spring 150 to contract, thereby re-engaging the teeth 140a, 140b with the teeth 128 on the guide rail 102. The stop mechanism used to prevent movement of the guide rail can be configured to operate independently of the actuation of the lever 110. Therefore, the bracket 106 can stop moving along the guide rail 102 before the lever 110 is actuated.

[0081] In addition, such as Figures 8 to 9 As shown, the sliding retaining clip 114 is held between guide rails 102 by a clamping mechanism 115, which includes bolts extending through flat plates extending on both sides of the bolts to each side of the guide rails 102. The plates may be spring-loaded to maintain tension. The plates and bolts form the clamp 115, which is configured to selectively loosen and tighten the sliding retaining clip 114 to allow the retaining clip 114 to be positioned along the guide rails 102 according to the size of the post accommodated by the clamping assembly 100.

[0082] Now for reference Figure 10 The diagram illustrates another clamp assembly 200 according to a different embodiment for application within a column housing (such as column housing 20), with lever 210 in a released position. Clamp assembly 200 may be similar to clamp assembly 100 described above. Similar to clamp assembly 100, clamp assembly 200 includes lever 210 configured to operatively move a first fluid assembly 204 to engage with a chromatographic column 216 and further push the column 216 to form a fluid seal with a second fluid assembly 208. Similar to the embodiments described above, the second fluid assembly 208 may include a system for connecting to a solvent tube 207 extending to fitting 209. Solvent tube 207 may be configured as a post-column attachment to provide solvent to the system prior to detection. The second fluid assembly 208 also includes an outlet port in parallel with the column, which may be connected to a fluid channel (not shown) that carries fluid from the column to a mass spectrometer (not shown). It should be understood that in this arrangement, the post-column attached solvent tube 207 is an option, not a necessity.

[0083] Furthermore, similar to clamp assembly 100, clamp assembly 200 includes an inlet heater 218, through which inlet pipe 220 supplies fluid that has passed through column 116 to a downstream portion of the fluid system. However, clamp assembly 200 includes a guide rail 202 and a stop mechanism 212 for locking bracket 206 to guide rail 202, which differs from the guide rail 102 and stop mechanism 112 of clamp assembly 100.

[0084] Figure 11 Depicting according to an implementation scheme Figure 10 A side view of the clamping assembly, with the clamping rod in the loaded position. Specifically, rod 210 rotates counterclockwise about pin 226. This rotation can be performed manually by a technician. Actuating rod 210 contacts the first fluid assembly 204 with the outlet end of column 216, thereby forming a fluid-impermeable seal between the first fluid assembly 204 and column 216. Furthermore, this rotation and actuation can simultaneously contact column 216 with second fluid assembly 208, thereby forming a fluid-impermeable seal between column 216 and second fluid assembly 208.

[0085] Figure 12 Depicting according to an implementation scheme Figures 10 to 11A perspective view of the lower side of the clamp assembly. As shown, the clamp assembly 200 includes a stop mechanism 212 having a manual button 230 for rotating a position-holding pawl 235 about a horizontal pin 236 extending through both the position-holding pawl 235 and the U-shaped structure 232. The frame 234 extends lower between each side of a double-rail structure of the guide rail 202. The frame 234 includes a U-shaped structure 232 on each side, through which the horizontal pin 236 extends, and about which the position-holding pawl 235 rotates. The U-shaped structure includes openings on the left and right sides that receive the horizontal pin 236. The position-holding pawl 235 is configured to rotate about the horizontal pin 236 in this manner. When the button 230 is pressed, the pawl 235 rotates about the vertical pin 236 to release the engagement arm ( Figure 13 As shown in the figure, the engaging arm has an array of locking teeth for engaging with an array of teeth arranged along the bottom of the guide plate 228. Figure 13 (As shown in the diagram). When button 130 is pressed, this allows bracket 206 to slide along guide rail 202. Although not shown in this view, it should be understood that the structure of stop mechanism 212 is mirrored on the other side of the double guide rail 202. Thus, each of manual button 230, retaining pawl 235, horizontal pin 236, and U-shaped structure 232 is included on the opposite side of guide rail 202, which is configured in the same way from... Figure 12 The view shown is hidden.

[0086] The view further shows a clamping mechanism 215, similar to or identical to clamping mechanism 115, which includes bolts extending through flat plates extending on both sides of the bolts to each side of the guide rail 202. The plates and bolts form clamp 215, which is configured to selectively loosen and tighten sliding retaining clip 214 to allow the retaining clip 214 to be positioned along the guide rail 102 according to the size of the post accommodated by clamping assembly 200.

[0087] Figure 13 Depicting according to an implementation scheme Figures 10 to 11An enlarged view of the stop mechanism 212 of the clamp assembly 100. As shown, the stop mechanism 212 includes a retaining pawl 235 that rotates about a horizontal pin 236 extending through the structure of the frame 234. The retaining pawl 235 extends to an engagement arm 238 having an array of locking teeth 240 arranged upward thereon. The locking teeth 240 are configured to engage with bottom teeth 229a of a guide plate 228. Top teeth 229b of the guide plate 228 are configured to engage with a bottom surface 205 of a guide rail 202. The bottom surface 205 may or may not have teeth that engage with the top teeth 229b. The engagement arm 238 is shown as including a chamber, hole, or recess for receiving a spring 242. The spring 242 may be configured to place an upward pressure on the engagement arm 238 to maintain the locking of the upward-facing locking teeth 240 of the engagement arm with the downward-facing teeth 229a of the guide plate 228. If the teeth on it are warned, the guide plate 228 can be a removable and replaceable component of the guide rail 202.

[0088] Therefore, in order to disengage from guide rail 202 and remove bracket 206, a technician will press the two buttons 230 of stop mechanism 212. This will cause pawl 235 to rotate counterclockwise around pin 236. Engaging arm 238 will then separate from guide rail plate 228. This disengages bracket 206 from guide rail 202, allowing bracket to slide freely along the axial direction of guide rail 202, while buttons 230 are pressed. When buttons 230 are released, due to the spring force from spring 242, pawl 235 rotates clockwise around pin 236, thereby re-engaging engagement arm 238 with guide rail plate 228.

[0089] While some implementation methods have been described in detail above, other modifications are possible. In some implementations, a fitting adapter may be provided for connecting a conversion chromatography column using a conventional sleeve-type fitting. Although a clamping assembly for the column housing has been described, in some implementations, the clamping assembly may alternatively or additionally be configured for a column manager, such as the ACQUITY UPLC available from Waters Corporation of Milford MA. ® Column manager.

[0090] Although the invention has been shown and described with reference to specific embodiments, those skilled in the art will understand that various changes in form and detail may be made without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims

1. A column shell for a chromatographic column, comprising: A cylindrical housing that extends along its length; A guide rail that extends within the cylindrical housing along the length thereof; A bracket movably attached to the guide rail, allowing the bracket to move along the guide rail, the bracket including an actuator and a stop mechanism; A first fluid assembly, configured to be moved by the actuator to engage with a chromatographic column received within the column housing; and A second fluid assembly is located near the end of the guide rail; The stop mechanism is configured to selectively prevent and allow movement of the bracket relative to the guide rail, the stop mechanism is configured to operate independently of the actuator, and the actuator is configured to: A first impermeable fluid seal is established between the first fluid assembly and the chromatographic column; as well as A second impermeable fluid seal is established between the second fluid assembly and the chromatographic column. The guide rail is a guide rod, and the bracket includes a hole through which the guide rod extends, wherein the bracket is configured to rotate about the guide rod to move the bracket into and out of multiple individual positions along the guide rail.

2. The column housing for a chromatographic column according to claim 1, wherein the stop mechanism includes a protrusion located on the bracket, the protrusion being engaged to a plurality of individual positions along the guide rail, each of the plurality of individual positions corresponding to a standard length of the chromatographic column.

3. The column housing for a chromatographic column according to claim 1, wherein the actuator is a manually operated cam loading rod.

4. The column housing for a chromatographic column according to claim 1, wherein the column housing accommodates a chromatographic column having at least one of a variety of column lengths and a variety of column diameters.

5. A clamping assembly, comprising: A guide rail that extends along its length and is configured to receive a first fluid assembly; and A bracket, movably attached to the guide rail such that the bracket moves along the guide rail, the bracket being configured to receive a second fluid assembly, the bracket including an actuator and a stop mechanism. The stop mechanism is configured to selectively prevent and allow movement of the bracket relative to the guide rail, the stop mechanism is configured to operate independently of the actuator assembly, and the actuator is configured to: The chromatographic column, received by the clamp assembly, is moved relative to the guide rail to form a first impermeable fluid seal between the chromatographic column and the first fluid assembly. The second fluid assembly is moved relative to the carriage body to form a second impermeable fluid seal between the second fluid assembly and the chromatographic column. The guide rail is a guide rod, and the bracket includes a hole through which the guide rod extends, wherein the bracket is configured to rotate about the guide rod to move the bracket into and out of multiple individual positions along the guide rail.

6. The clamp assembly of claim 5, wherein the stop mechanism includes a protrusion located on the bracket, the protrusion being engaged with a plurality of individual positions along the guide rail, each of the plurality of individual positions corresponding to a standard length of the chromatographic column.

7. The clamping assembly of claim 5, wherein the actuator is a manually operated cam loading rod.

8. The clamp assembly of claim 5, wherein the bracket accommodates a chromatographic column having at least one of a variety of column lengths and a variety of column diameters.

9. A method for establishing a fluid-impermeable seal, comprising: Provide a clamping assembly according to any one of claims 5-8; The first chromatographic column is received via the clamp assembly; Move the bracket along the guide rail of the clamp assembly to a first position corresponding to the length of the first chromatographic column; The stop mechanism of the bracket prevents the bracket from moving relative to the guide rail at the first position; After preventing movement, the actuator engages the bracket; By engaging the actuator, a first impermeable fluid seal is established between the first fluid assembly and the first chromatographic column; as well as The engagement of the actuator establishes a second impermeable fluid seal between the second fluid assembly and the first chromatographic column.

10. The method of claim 9, further comprising: Release the stop mechanism of the bracket; Move the bracket along the guide rail of the clamp assembly; Remove the first chromatographic column from the clamp assembly; The second chromatographic column is received via a clamp assembly; Move the bracket along the guide rail of the clamp assembly to a second position corresponding to the length of the second chromatographic column; The stop mechanism of the bracket prevents the bracket from moving relative to the guide rail at the second position; After preventing movement, the actuator engages the bracket; Through the engagement of the actuator, a third impermeable fluid seal is established between the first fluid assembly and the second chromatographic column; as well as The engagement of the actuator establishes a fourth impermeable fluid seal between the second fluid assembly and the second chromatographic column.

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