Patent Application
20080314412
The invention herein described relates generally to liquid sample (LC) or liquid chromatography/mass spectrometry (LC/MS) analytical systems.
Analytical sampling systems are known, particularly in the biotechnology industry. A common feature of such systems is the use of a robotic or other motion control device to either move a fluid aspirating/dispensing syringe about a deck of vessels or other deck components, such as wash stations, reagent troughs and injection valves for analytical sampling devices.
A significant factor affecting analytical sampling device performance in such systems is the amount of remnant carry-over from previous samples to subsequent injections. Sample carry-over confounds the results of subsequent runs adding to overall analytical uncertainty. Carry-over arises from many aspects of liquid chromatography (LC) or liquid chromatography/mass spectrometry (LC/MS) equipment and operations. These include, but are not limited to incomplete cleaning/flushing to waste of surfaces routinely exposed to samples and other contaminants; unswept areas in the sample flow path into which sample molecules diffuse and build up over several runs until they concentrate enough to diffuse back into the bulk flow and pollute subsequent runs; uncleaned areas in the sampling path that only occasionally, through statistical incidence, come in contact with sampling elements; incomplete LC column elution resulting in buildup of highly retained compounds until they eventually migrate to the end of the column and exhibit themselves as spurious “ghost” peaks in the elution profile or mass spectrum or continuously bleed off of the column disrupting the signal baseline making peak area estimation difficult and uncertain; overspraying at the MS source causing buildup and contamination of inlet orifices, skimmers, and ion optics; and occasional samples containing contaminants for which the analysis was not designed to efficiently clear from the system. Some of these causes are insidious and only exhibit themselves sporadically over the course of several runs while others are more obvious and demonstrate themselves routinely from run to run.
One known mechanism used to effect injection port washing uses the injection syringe itself. In this case, after injecting the sample, the syringe barrel is washed internally and its probe is washed both internally and externally at a separate syringe wash area located within the sampling device's workspace. The clean syringe is then charged with cleaning solution, moved back to the injection port, inserted into the port, and the cleaning solution forced through the injection mechanism. At this point, the syringe is considered to have become contaminated since it might have contacted residual sample clinging to the injection port as it was being inserted. Consequently, the syringe must once again be washed both internally and externally to prepare it for aspirating the next sample.
Although the foregoing technique is nominally adequate for flushing the contaminated elements distal to the syringe to injection port seal, it has several drawbacks. The process is slow. The many syringe actuations required to clean the syringe, clean the injection port, and then clean the syringe again, greatly reduces the syringe seal lifetime. The injection port may remain contaminated proximal to the syringe to injection port seal despite the cleaning process. As the syringe containing the next sample is inserted into the injection port it might slide along the contaminated wall as it finds its seat, dragging the contaminant into the system with it. The additional syringe insertions into the injection port also reduces the injection port sealing surface lifetime resulting in only about half the number of samples being able to be injected before the seal needs to be replaced.
Another washing technique employs a dedicated injection port wash mechanism which does not require assistance by the device's injection syringe. One such mechanism is disclosed in U.S. Pat. No. 6,526,812. This mechanism includes a fixed wash chamber bounded by the walls of the injection port on the sides, with an inlet port for introducing washing solution. The top of the wash chamber is sealed by a penetrable, self-sealing septum. Consequently, during sample injection, the injection needle of the syringe must be inserted through the septum.
While this dedicated wash mechanism eliminates some of the disadvantages associated with the syringe-based washing technique, it introduces its own disadvantages. One problem is that of the septum being cored by the syringe, this resulting in clogged syringes and a leaky septum. Another disadvantage is the deposition of contaminating drops on the top of the septum which might be dragged or pushed through to the injection area on subsequent samples, resulting in carry-over.
This present invention eliminates one or more of the drawbacks associated with prior injection port wash mechanisms and techniques. In particular, the invention provides a self-cleaning injection port assembly that eliminates the need for the above-described septum and the disadvantages associated therewith. This is effected by the use of a movable wash chamber closure device for opening and closing an injection needle entry passage of an injection port wash chamber. For sample injection, the wash chamber closure device can be moved clear of the path along which the injection needle passes through the wash chamber into the injection port, thereby enabling insertion of the injection needle into the injection port. For washing, the wash chamber closure device is moved to a position closing the entry passage of the injection port wash, after which cleaning fluid may be circulated through the injection port for cleaning.
Accordingly, the present invention provides a self-cleaning injection port assembly for use with a liquid chromatography injection valve, comprising an injection port body and a wash chamber closure device. The injection port body defines an interior chamber having an upper chamber portion and a lower chamber portion, an entry opening through which an injection needle can be inserted into the interior chamber, a wash port connected to the upper chamber between the entry opening and the lower chamber portion, and an outlet communicating with the lower chamber portion. The lower chamber portion has associated therewith a needle sealing surface surrounding a portion of the lower chamber portion for effecting a seal with the injection needle when inserted into the interior chamber, and the upper chamber portion has, at least in the region thereof located between the wash port and the entry opening, a cross-sectional size greater than a cross-sectional area bounded by the needle sealing surface whereby in such region the injection needle, when inserted therein, will be spaced from the interior wall of the upper chamber to preclude the transfer of any foreign material clinging to the exterior surface of the needle from touching the interior wall of the upper chamber. The wash chamber closure device is movable between a first position allowing an injection needle to be inserted through the entry opening into the interior chamber of the injection port body and into sealing engagement with the needle sealing surface, and a second position closing the entry open end of the chamber after the injection needle has been withdrawn from the interior chamber, whereby a wash fluid may be passed through the wash port, upper chamber, lower chamber and outlet for cleaning.
In a preferred embodiment, the wash chamber closure device includes a seal for sealing to the interior wall of the upper chamber, and a swing arm is used to move the washing device between the first and second positions. The swing arm may move the washing device laterally relative to an axis and along the axis.
More generally, the present invention provides a self-cleaning injection port assembly for use with a liquid chromatography injection valve, comprising an injection port body including an interior wash chamber having an entry opening for insertion of an injection needle therethrough, and a wash chamber closure device movable between a first position allowing the injection needle to be inserted through the entry opening into the interior chamber of the injection port body and a second position closing the entry opening of the chamber after the injection needle has been withdrawn from the interior chamber for cleaning. Cleaning fluid may be supplied to and/or withdrawn from the wash chamber via a wash port provided in the wash chamber closure device and/or in the port body.
According to another aspect of the invention, there is provided a method of cleaning an injection port assembly, wherein the injection port assembly includes an injection port body having an interior wash chamber with an entry opening for insertion of an injection needle therethrough. The method comprises the steps of moving a washing device from a first position allowing the injection needle to be inserted through the entry opening into the interior chamber of the injection port body to a second position closing the entry opening of the chamber after the injection needle has been withdrawn from the interior chamber, and causing cleaning fluid to flow through the interior chamber when the washing device is in the second position closing the entry opening. The cleaning fluid may be introduced into the interior chamber through a flow passage in the washing device or a flow passage in the injection port body.
Further features of the invention will become apparent from the following detailed description when considered in conjunction with the drawings.
In the annexed drawings,
Referring now in detail to the drawings and initially to
The injection port body 24 has at a top end thereof an entry opening 34 through which an injection needle 36 of a syringe 38 can be inserted downwardly into the injection port body 24 (as shown in
The carriage 42 has a forward swing arm portion 54 to which the wash chamber closure device 26 is mounted, and a rear arm that has a guide pin 58 engaged in a cam slot 60 in a cam plate 62 mounted to the upright portion 46 of the base 22. As the carriage is lowered along the lead screw of the lead screw and nut assembly, the cam slot first guides the carriage downwardly out of a park position, then rotates the carriage about the axis of the lead screw to vertically align the closure device 26 with the entry opening 34, and then holds the carriage against further rotation to guide the closure device 26 into the entry opening 34. The closure device 26 will be guided in an opposite manner during retraction of the closure device 26 from the entry opening 34.
Sensors 66 and 68 are provided to detect the park and closed positions of the closure device 26 during raising and lowering of the closure device 26. To this end, the distal end of the rear arm may be provided with a vertical member 70, the ends of which respectively will move into the slots of sensors mounted to the cam plate at opposite ends of the cam slot 60. The sensors may be of any suitable type, such as optical beam sensors, hall effect sensor, contact sensors, etc. The sensors provide feedback to the controller so that the controller knows when the closure device 26 has reached its park or closed positions so that it can stop further operation of the motor.
As shown in
The opening at the lower end of the sleeve seal 78 communicates with an outlet 80 of the injection port that may be connected in a conventional manner to an injection valve and associated tubing and/or passages. The injection body also includes a wash port 82 opening to a side of the upper chamber 74 between the lower chamber portion and the entry opening 34. The wash port may be connected by suitable means to a source of cleaning fluid or a reservoir or drain for cleaning fluid, depending on the desired flow path of cleaning fluid through the injection port assembly.
The upper or wash chamber 74 opens to the top of the injection port body 24 via the entry opening 34 through which the injection needle 36 can be inserted into the interior chamber as shown in
For further details of a suitable syringe and its manner of interfacing with control components and functional stations of an analytical system or systems, reference may be had to International Patent Application No. PCT/US06/02845 which is hereby incorporated herein by reference. For instance, an injection procedure may be effected under the control of the syringe 38 that may include a suitably programmed logic control device. The interface device may also provide power to the syringe 38 when held in the injection port assembly. It is noted, however, that other types of syringes may be used with the self-washing injection port device, including syringes that are inserted manually as well as those used by conventional autosampling systems where the syringe is tethered to a gantry system. In the former case, the user could inject by hand and click a “Wash Port” button on a software screen to begin a port washing sequence and in the latter case, a port washing sequence could be triggered by the main control software once the injection has competed and the gantry and syringe have moved out of the way.
As best seen in
After a sample injection the syringe 38 can be removed and the wash chamber closure device 26 moved from its stowage position to its position closing the entry opening 34 of the injection port body 24 as shown in
The seal 90 between the closure device 26 and the wash chamber 74 may be made at surfaces proximal to any surface that could possibly come in contact with the syringe 38 or any contaminating material carried by the syringe 38. Thus, all surfaces within the injection port assembly that can possibly become contaminated during the injection process can be completely washed during the washing process. Wash solution may be directed through the wash port 82 and into the interior chamber of the injection port body for passage out through the outlet 80 to the injection valve, resulting in complete cleaning and minimal carryover.
Those skilled in the art will appreciate that various modifications can be made to the illustrated exemplary injection port wash assembly while still using one or more principles of the present invention. For example, the wash port may be replaced by or supplemented by a wash port 94 provided in the closure device 96 as seen in
Alternatively, a hard seal may be provided between a modified closure device 106 and the tapered mouth 108 of the wash chamber 74 as shown in
As will be appreciated, any of the illustrated sealing arrangements between the closure device and the wash chamber can be used interchangeably, as desired.
Although the invention has been shown and described with respect to a certain embodiment or embodiments, it is obvious that equivalent alterations and modifications will occur to others skilled in the art upon the reading and understanding of this specification and the annexed drawings. In particular regard to the various functions performed by the above described elements (components, assemblies, devices, compositions, etc.), the terms (including a reference to a “means”) used to describe such elements are intended to correspond, unless otherwise indicated, to any element which performs the specified function of the described element (i.e., that is functionally equivalent), even though not structurally equivalent to the disclosed structure which performs the function in the herein illustrated exemplary embodiment or embodiments of the invention. In addition, while a particular feature of the invention may have been described above with respect to only one or more of several illustrated embodiments, such feature may be combined with one or more other features of the other embodiments, as may be desired and advantageous for any given or particular application.
This application claims the benefit of U.S. Provisional Application Nos. 60/742,386 filed Dec. 5, 2005, 60/748,853 filed Dec. 7, 2005, and 60/803,295 filed May 26, 2006, all of which are hereby incorporated by reference in their entireties.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US06/46403 | 12/4/2006 | WO | 00 | 9/9/2008 |
| Number | Date | Country | |
|---|---|---|---|
| 60742386 | Dec 2005 | US | |
| 60748853 | Dec 2005 | US | |
| 60803295 | May 2006 | US |
