Needle driver, system and method

Abstract

A liquid chromatography sample manager includes a thermal processing chamber; a sample tray 110 mounted in the thermal processing chamber; and a needle drive comprising a base 230 having a shaft configured to rotate about a vertical axis, the base being attachable to the interior of a sample manager of a liquid chromatography system. The needle drive also includes a needle assembly attached to the base, the needle assembly including a sample needle 122 and a drive system 112 attached to the base, the drive system including a sample needle motor configured to impart vertical movement to the sample needle.

Description

[0001] Related applications

[0002] This application claims the benefit of the prior filing date of U.S. Provisional Patent Application Serial No. 62 / 990,653, filed on March 17, 2020, entitled “Needle Drive, System and Method,” which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention generally relates to liquid chromatography systems. More particularly, the present invention relates to liquid chromatography sample managers and associated needle drive systems and methods. Background Art

[0004] Chromatography is a group of techniques that separate mixtures into their components. For example, in a liquid chromatography system, a pump draws in a mixture of liquid solvents and delivers it to a sample manager, where the injected sample awaits its arrival. In an isocratic chromatography system, the composition of the liquid solvent remains constant, while in a gradient chromatography system, the solvent composition changes over time. A mobile phase, consisting of the sample dissolved in a solvent mixture, passes through a column, known as the stationary phase. By passing the mixture through the column, the various components in the sample separate from one another at different rates and, therefore, elute from the column at different times. A detector receives the elution from the column and produces an output from which the type and amount of the analyte can be determined.

[0005] A sample can be provided to a sample manager prior to being provided to a liquid chromatography system. The sample manager can be configured to prevent the sample from being degraded or otherwise damaged while being provided to the liquid chromatography system. The sample manager regularly interacts with technicians and must therefore be user-friendly, reliable, accurate, dependable, serviceable, and cost-effective. Improved sample managers, systems, and methods would be welcome in the art. Summary of the Invention

[0006] In one embodiment, a liquid chromatography system includes: a solvent delivery system; a sample manager having a thermal treatment chamber, the thermal treatment chamber including: a sampling mechanism mounted within the thermal treatment chamber, the sampling mechanism including: a sample tray; a needle drive including: a base including a shaft configured to rotate about a vertical axis, the base attachable to an interior of the sample manager of the liquid chromatography system; a needle assembly attached to the base, the needle assembly including a sample needle; and a drive system attached to the base, the drive system including a sample needle motor configured to impart vertical movement to the sample needle; and a sample delivery system fluidly connected to the solvent delivery system, the sample delivery system configured to transfer a first sample from a first sample vial holder located in the sample tray to a chromatographic flow stream; a liquid chromatography column located downstream of the solvent delivery system and the sample delivery system; and a detector located downstream of the liquid chromatography column.

[0007] Additionally or alternatively, the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor, the puncture needle motor being configured to impart vertical movement to the puncture needle independently of the vertical movement of the sample needle, and wherein the needle assembly further comprises a stripper foot movable in a vertical direction, wherein the stripper foot comprises an opening, the puncture needle being configured to extend through the opening during puncture.

[0008] Additionally or alternatively, the needle driver further comprises a sensor system comprising a flexible circuit board attached to the base and configured to bend as the shaft rotates about the vertical axis, the sensor system further comprising: a stripper foot movement sensor configured to determine that the stripper foot has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved in a vertical direction to a sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved in a vertical direction to a puncture needle original position.

[0009] Additionally or alternatively, the needle driver further comprises a spindle motor configured to rotate the spindle about the vertical axis; and a magnetic encoder configured to maintain a precise rotational position of the spindle of the base.

[0010] Additionally or alternatively, the base of the needle driver further comprises a needle arm housing that supports the shaft at at least two locations, the needle arm housing being attached to the interior of the thermal processing chamber of the sample manager using a plurality of accessible bolts.

[0011] Additionally or alternatively, the needle assembly is attachably removable from the base of the needle driver using a plurality of accessible bolts, wherein the sample manager further comprises a door that provides a technician with access to the thermal processing chamber when opened, wherein the needle driver is removable from the thermal processing chamber through the door.

[0012] In another embodiment, a liquid chromatography sample manager includes: a thermal processing chamber; a sample tray mounted in the thermal processing chamber; a needle drive including: a base including a shaft configured to rotate about a vertical axis, the base attachable to an interior of a sample manager of a liquid chromatography system; a needle assembly attached to the base, the needle assembly including a sample needle; and a drive system attached to the base, the drive system including a sample needle motor configured to impart vertical movement to the sample needle; and a sample delivery system configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatography flow stream;

[0013] Additionally or alternatively, the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor, the puncture needle motor being configured to impart vertical movement to the puncture needle independently of the vertical movement of the sample needle, and wherein the needle assembly further comprises a stripper foot movable in a vertical direction, wherein the stripper foot comprises an opening, the puncture needle being configured to extend through the opening during puncture.

[0014] Additionally or alternatively, the needle driver further comprises a sensor system comprising a flexible circuit board attached to the base and configured to bend as the shaft rotates about the vertical axis, the sensor system further comprising: a stripper foot movement sensor configured to determine that the stripper foot has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved in a vertical direction to a sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved in a vertical direction to a puncture needle original position.

[0015] Additionally or alternatively, the needle driver further comprises a spindle motor configured to rotate the spindle about the vertical axis; and a magnetic encoder configured to maintain a precise rotational position of the spindle of the base.

[0016] Additionally or alternatively, the base of the needle driver further comprises a needle arm housing that supports the shaft at at least two locations, the needle arm housing being attached to the interior of the thermal processing chamber of the sample manager using a plurality of accessible bolts.

[0017] Additionally or alternatively, the needle assembly is attachably removable from the base of the needle driver using a plurality of accessible bolts, wherein the liquid chromatography sample manager further comprises a door that, when opened, provides a technician with access to the thermal processing chamber, wherein the needle driver is removable from the thermal processing chamber through the door.

[0018] In another embodiment, a needle drive for a liquid chromatography system includes: a base including a shaft configured to rotate about a vertical axis, the base attachable to an interior of a sample manager of the liquid chromatography system; a needle assembly attached to the base, the needle assembly including a sample needle; and a drive system attached to the base, the drive system including a sample needle motor configured to impart vertical movement to the sample needle;

[0019] Additionally or alternatively, the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor configured to impart vertical movement on the puncture needle independently of the vertical movement of the sample needle.

[0020] Additionally or alternatively, the needle assembly further comprises a stripper foot movable in a vertical direction, wherein the stripper foot comprises an opening, the piercing needle being configured to extend through the opening during piercing.

[0021] Additionally or alternatively, the needle assembly further includes a sensor system comprising a flexible circuit board attached to the base and configured to flex with rotation of the shaft about the vertical axis.

[0022] Additionally or alternatively, the sensor system further comprises: a stripper foot movement sensor configured to determine that the stripper foot has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved in a vertical direction to a sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved in a vertical direction to a puncture needle original position.

[0023] Additionally or alternatively, the needle driver includes a spindle motor configured to rotate the spindle about the vertical axis.

[0024] Additionally or alternatively, the needle driver further comprises a magnetic encoder configured to maintain a precise rotational position of the shaft of the base.

[0025] Additionally or alternatively, the base further comprises a needle arm housing that supports the shaft at at least two locations, the needle arm housing being attachable to the interior of the sample manager of the liquid chromatography system using accessible bolts.

[0026] Additionally or alternatively, the needle assembly is attachably removable from the base using accessible bolts. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The above and other advantages of the present invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which like reference numerals refer to like elements and features throughout the various figures. For clarity, not every component is labeled in every figure. The drawings are not necessarily drawn to scale, emphasis instead being placed upon illustrating the principles of the invention.

[0028] Figure 1 Depicted is a schematic diagram of a liquid chromatography system including a sample manager, according to one embodiment.

[0029] Figure 2 Depicted is a method according to one embodiment comprising Figure 1 A perspective view of a liquid chromatography system with a sample manager.

[0030] Figure 3 Depicted according to one embodiment Figure 1 and Figure 2 Another perspective view of the interior of the sample manager.

[0031] Figure 4 Depicts a first calibration position according to one embodiment. Figure 1 and Figure 2 A perspective view of the interior of the sample manager.

[0032] Figure 5 Depicts a second calibration position according to one embodiment. Figure 1 and Figure 2 A perspective view of the interior of the sample manager.

[0033] Figure 6 Depicted is a perspective view of a needle arm disassembled from the interior of a sample manager, according to one embodiment.

[0034] Figure 7 Depicts a disassembled needle assembly according to one embodiment. Figure 6 Perspective view of the needle arm.

[0035] Figure 8 Depicted according to one embodiment Figure 6 Side view of the needle arm.

[0036] Figure 9 Depicted according to one embodiment Figure 6 and Figure 8 Top view of the needle arm.

[0037] Figure 10Depicted is a method for Figure 9 The arrow 10-10 intercepted Figure 6 、 Figure 8 and Figure 9 Side cross-sectional view of the needle arm. DETAILED DESCRIPTION

[0038] Reference in this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present teachings. References to specific embodiments within this specification are not necessarily all referring to the same embodiment.

[0039] This teaching will now be described in more detail with reference to the exemplary embodiments of this teaching as shown in the accompanying drawings. Although this teaching has been described in conjunction with various embodiments and examples, this teaching is not intended to be limited to such embodiments. In contrast, this teaching encompasses various alternatives, modifications, and equivalents, as will be understood by those skilled in the art. Those of ordinary skill in the art who can use this teaching will recognize additional embodiments, modifications, and embodiments within the scope of this disclosure as described herein, as well as other areas of use.

[0040] As described herein, before performing a liquid chromatography run, a technician loads an array of vials containing samples onto a sample vial rack, places the sample vial rack onto a drawer, and slides the drawer into a bay within a sample tray in a thermal processing chamber of a sample manager system. The sample manager system includes a sample delivery system configured to transfer samples from the sample vial rack into the chromatographic flow stream. The thermal processing chamber includes a sampling mechanism comprising a rotating sample tray with improved sample capacity and sampling accuracy. The sampling needle, which is part of the sampling mechanism, is located on a rotating needle arm that, in conjunction with the rotating sample tray, provides complete needle coverage over the bay within the sample tray. The entire needle arm is positioned and dimensioned within the thermal processing chamber so that it can be removed from the front door of the thermal processing chamber for easy maintenance. Encoders on the rotating needle arm and the rotating sample tray maintain sufficient resolution for accurate sampling. These rotating needle arms can be calibrated using a calibration process to ensure accuracy.

[0041] The features of the sample delivery system and sample manager thermal chamber described herein can be applied to any liquid chromatography system configured to deliver a sample into a chromatographic flow stream. As an example, Figure 1 An embodiment of a liquid chromatography system 10 for separating a mixture into its components is shown. The liquid chromatography system 10 includes a solvent delivery system 12 in fluid communication with a sample manager 14 (also known as an injector or autosampler) via tubing 16. The sample manager 14 is in fluid communication with a chromatography column 18. A detector 21, such as a mass spectrometer, is in fluid communication with the column 18 to receive the eluted solution.

[0042] Solvent delivery system 12 includes a pumping system 20 in fluid communication with a solvent reservoir 22, from which it draws solvent (liquid) via tubing 24. In one embodiment, pumping system 20 is embodied as a low-pressure mixing gradient pumping system having two pumps fluidically connected in series. In a low-pressure gradient pumping system, solvent mixing occurs before the pumps, and solvent delivery system 12 includes a mixer 26 in fluid communication with solvent reservoir 22 to receive each solvent in metered proportions. This mixing of the solvent (mobile phase) composition varies over time (i.e., a gradient).

[0043] Pumping system 20 is in fluid communication with mixer 26 to draw a continuous gradient flow therefrom for delivery to sample manager 14. Examples of solvent delivery systems that may be used to implement solvent delivery system 12 include, but are not limited to, the ACQUITY Binary Solvent Manager and the ACQUITY Quaternary Solvent Manager manufactured by Waters Corp. of Milford, Mass.

[0044] The sample manager 14 may include a syringe valve 28 having a sample loop 30. The sample manager 14 operates in one of two states: a load state and an inject state. In the load state, the position of the syringe valve 28 causes the sample manager to load a sample 32 into the sample loop 30. Sample 32 is drawn from a vial held in a vial holder. A "vial holder" herein refers to any device configured to hold a sample vial, such as a well plate, a vial holder, etc. In the inject state, the position of the syringe valve 28 changes, causing the sample manager 14 to introduce the sample in the sample loop 30 from the solvent delivery system into the continuously flowing mobile phase. The mobile phase thus carries the sample to the column 18. In other embodiments, a flow-through needle (FTN) method may be utilized instead of a fixed-loop sample manager. Using the FTN method, the sample is drawn into a needle, which is then moved into a seal. The valves can then be switched to align the needle with the solvent delivery system.

[0045] Liquid chromatography system 10 further includes a data system 34 in signal communication with solvent delivery system 12 and sample manager 14. Data system 34 includes a processor 36 and a switch 38 (e.g., an Ethernet switch) for handling signal communication between solvent delivery system 12 and sample manager 14. Signal communication between the various systems and instruments can be electrical or optical, using either wireless or wired transmission. A host computing system 40 is in communication with data system 34, allowing technicians to download various parameters and configuration files (e.g., inlet gas velocity profiles) to data system 34.

[0046] Figure 2 A perspective view of a liquid chromatography system 10 is shown, which includes a sample manager 14, a detector 21, a chromatography column 18, a solvent delivery system 12, and a solvent 22. Each of the sample manager 14, the detector 21, the chromatography column 18, and the solvent delivery system 12 can include a housing or body within which various features can be housed, such as a data system 34, a sample loop 30 and a syringe valve 28, a pumping system 20, a mixer 26, and tubing 24. The various components 12, 14, 18, 19, 21, 22 can be interconnected with fluidic tubing and in signal communication with the system's data system 34. The liquid chromatography system 10 is shown with the solvent delivery system 12, the sample manager 14, the chromatography column 18, the detector 21, and a tray for holding the solvent 22 stacked together.

[0047] Figure 3 Depicted according to one embodiment Figure 1 and Figure 2 14. As shown in the figure, the sampling mechanism 100 includes a sample tray 110 attached to a reference base 112. A vertical frame 114 is attached to and extends perpendicular to the reference base 112. A needle arm 116 is attached to the vertical frame 114. The needle arm 116 includes a puncture needle 122 (such as Figure 4 ) and a sample needle (not shown) as part of a sample delivery system that is in fluid communication with the solvent delivery system 12. The sample needle can be configured to remove a sample from a sample bottle 33 (e.g., Figure 2 1 (not shown) to obtain or otherwise extract a sample 32. Thereafter, the sample delivery system of the liquid chromatography system 10 is configured to transfer the sample 32 into the chromatographic flow stream and to the column 18 located downstream of the sample delivery system, and then to the detector 21 located downstream of the column 18. The sample vial 33 can be one of many vials located in up to four sample vial holders (not shown) on the sample tray 110.

[0048] The sample tray 110 can be configured to rotate 360 degrees about a first vertical axis A1, while the needle arm 116 can be configured to rotate at least partially about a second vertical axis A2. These two rotations can provide adequate coverage of all sample vial holders 124 within the sample tray 110 by the needle arm 116. The rotation of the needle arm 116 combined with the rotation of the sample tray 110 can thus be configured to move the puncture needle 122 into position to access any location on the sample tray 110 that holds a sample vial 33 within a sample vial holder.

[0049] As shown, sample tray 110 comprises a circular frame comprising four compartments: a first support compartment 126a, a second support compartment 126b, a third support compartment 126c, and a fourth support compartment 126d. The support compartments 126a, 126b, 126c, and 126d are equidistantly spaced around the circumference of the circular sample tray 110. In other words, the support compartments 126a, 126b, 126c, and 126d are arranged 90 degrees from one another around the circular sample tray 110. As described above, the rotating needle arm 116, in conjunction with the rotation of the sample tray 110, is configured to move the puncture needle 122 directly over any position covered by the respective circumferences of the respective support compartments 126a, 126b, 126c, and 126d. The tray may include four compartments as shown, but in other embodiments, it may also include three compartments or extend to even more than four compartments. The compartments may be equidistant from one another or may be staggered in other ways around the circumference of the circular sample tray 110.

[0050] Each of the rack bays 126a, 126b, 126c, 126d is shown as a drawer that slides into and out of a bay drawer receiver 128a, 128b, 128c, 128d. The rack bays 126a, 126b, 126c, 126d can be configured to be pulled radially outward from the respective bay drawer receivers 128a, 128b, 128c, 128d to facilitate loading of sample bottle racks into and out of the front door 130 (e.g., a sample tray) of the sample tray. Figure 2 128d). The integration of the rack bays 126a, 126b, 126c, 126d and the corresponding bay drawer receivers 128a, 128b, 128c, 128d can be configured to stop the rack bays 126a, 126b, 126c, 126d before the rack bays 126a, 126b, 126c, 126d are completely disconnected from the bay drawer receivers 128a, 128b, 128c, 128d. Alternatively, the frame of the sampling mechanism 100 can include a structure that prevents the rack bays 126a, 126b, 126c, 126d from being completely disconnected from the bay drawer receivers 128a, 128b, 128c, 128d.

[0051] Each of the rack bays 126a, 126b, 126c, 126d is configured to receive a sample bottle rack. The sample manager 14 can be configured to receive and process samples in all four rack bays 126a, 126b, 126c, 126d. In addition to sliding in and out of the bay drawer receivers 128a, 128b, 128c, 128d via a track system, the rack bays 126a, 126b, 126c, 126d can include a magnet located underneath that is configured to magnetically hold the sample bottle rack in place within the rack bays 126a, 126b, 126c, 126d. Corresponding magnets can be located radially inwardly within the rack bays 126a, 126b, 126c, 126d to further ensure that the rack bays 126a, 126b, 126c, 126d are properly seated (i.e., fully inserted) relative to the bay drawer receivers 128a, 128b, 128c, 128d. The leaf spring 132 can be configured to bias a received sample disc toward the leftmost wall of the corresponding rack bay 126a, 126b, 126c, 126d, while the magnetic structure holds the received sample disc against the radially inward wall of the corresponding rack bay 126a, 126b, 126c, 126d.

[0052] Sample tray 110 includes a central opening 134 for receiving a column 135, around which sample tray 110 is configured to rotate about a vertical axis A1. Sample tray 110 also includes additional openings 136 disposed around its perimeter between rack compartments 126a, 126b, 126c, and 126d. These additional openings are configured to receive and hold larger, individual vials (not shown) or other samples. Needle arm 116 (and its needle) can be configured to be positioned above each of the peripheral additional openings 136.

[0053] The sample tray 110 is shown mounted to a reference base 112. The reference base 112 can be a metal plate mounted to a thermal chamber frame (not shown) within the sample manager 14. The reference base 112 can include an opening through which deflection limiting posts 120 extend. The deflection limiting posts 120 can be configured to prevent the sample tray 110 from deflecting beyond a specific distance relative to the reference base 112 before coming to rest. The deflection limiting posts 120 can be keyed to channels in the bottom of the sample tray 110 and can act as bearings to allow the sample tray 110 to rotate about the reference base 112. Rotation of the sample tray 110 about the reference base 112 can be generated by a motor 150 disposed on the reference base 112 near the perimeter of the sample tray 110. The reference base 112 also includes a plurality of threaded openings configured to receive bolts for attaching right-angle brackets 118 on each side. The right-angle brackets 118 can be configured to attach the vertical frame 114 to the reference base 112 in a vertical orientation. An encoder (not shown) may be further attached to the sample disk 110 to maintain the position of the sample disk 110 relative to the reference base 112 .

[0054] The vertical frame 114 is attached to the reference base 112 so that the vertical frame 114 extends across the circumference of the sample tray 110. Given that this position is above the sample tray 110, the vertical frame 114 includes an opening 140 (e.g., Figure 4 The sample tray 110 and any received sample bottle carriers 124a, 124b and any received sample bottles 33 are configured to pass through the opening or cutout. The opening 140 is sized high enough to receive the tall sample bottle holder 124b without interference. The vertical frame 114 forms a surface above the opening 140 on which the needle arm 116 is mounted.

[0055] Needle arm 116 is shown to include a drive mechanism 142 and a motor 144. Motor 144 is configured to rotate about the axis of a rotating belt 148, which in turn rotates pulley 152. Rotation of pulley 152 can be configured to rotate needle arm 116 about a second vertical axis A2. The rotation of needle arm 116 can be independent of the rotation of sample disk 110 and can be about a vertical axis A2 that is different from the vertical axis A1 about which sample disk 110 rotates.

[0056] Now see Figure 4 , according to one embodiment, is shown in a first calibration position Figure 1 and 2 A perspective view of the interior of sample manager 14. Figure 4 The first calibration position shown is the needle arm 116 relative to Figure 3The position shown is a position rotated counterclockwise about the second vertical axis A2. As shown, a shaft 154 extends through the pulley 152, which is attached to and configured to rotate with the pulley 152. The shaft 154 is connected to a rotating plate 155, which is configured to rotate with the shaft 154 and rotate the needle assembly 190. The shaft 154 includes a biasing spring 232. A removable needle arm housing 158 is attached to the vertical frame 114. The removable needle arm housing 158 includes a horizontal plate 160 extending just above the opening 140 in the vertical frame 114. The horizontal plate 160 includes a bushing 156 that is configured to receive the base of the shaft 154 and maintain the shaft 154 aligned with the second vertical axis A2. The needle arm housing 158 is removably attached to the vertical frame 114 using a plurality of accessible bolts 162. The accessible bolts 162 are accessible through the door 130 of the sample manager 14. This may allow the entire vertical frame 114 and needle arm 116 and all components thereof to be easily removed through the door 130 during maintenance or parts replacement.

[0057] Needle arm 116 also includes a magnetic encoder 146. Magnetic encoder 146 can be configured to determine the rotational position of needle arm 116 to any tolerances required for accurate positioning of puncture needle 122. Similarly, motor 150 can be equipped with an encoder for determining the rotational position of sample tray 110. Both encoders in the system can communicate with a control system (e.g., data system 34) for calibrating and controlling the movement of needle arm 116 and sample tray 110. While magnetic encoders can be utilized, other encoders, such as optical encoders, are contemplated.

[0058] The needle arm 116 is shown to include two separate motors 164a, 164b that are configured to rotate two separate drive shafts. The first motor 164a is configured to rotate the first drive shaft 236 (e.g., Figure 6 and Figure 8 The second motor 164b is configured to rotate the second drive shaft 238 (as shown) to move the first drive shaft on the puncture needle 122. Figure 6 and Figure 8 The second drive shaft (shown) rotates, which moves the sample needle (not shown). A first motor 164a and a second motor 164b can be attached to the needle arm 116 so that the motors 164a, 164b rotate together with the needle arm 116. The puncture needle 122 can operate in conjunction with the sample needle to puncture any material or membrane covering the sample vial. The two motors 164a, 164b can be configured to operate independently and can be controlled and programmed by the control system and / or data system 34 for operating routines.

[0059] The needle assembly 190 of the needle arm includes a plate 192 having two accessible bolts 194 that are accessible by a technician opening the door 130 of the sample manager 14. After loosening the accessible bolts 194, the technician can remove the needle assembly 190 and the attached motors 164a, 164b from the needle mechanism base 230. The needle assembly 190 and motors 164a, 164b can be removed through the door 130 of the sample manager 14 without removing the needle mechanism base 230. Similarly, the motors 164a, 164b can be easily removed from the needle arm 116 by removing one or more accessible motor bolts 196 from the plate 192. This can allow the motors 164a, 164b to be easily replaced or removed for maintenance through the front door 130 of the sample manager 14 without removing other components of the needle arm 116.

[0060] The sample delivery system may also include a fluid tube (not shown) positioned between the sample needle and the liquid chromatography column 18. The fluid tube may include a coiled portion configured to expand and contract during rotation of the needle arm 116 about the second vertical axis A2. The coiled portion may extend between the top of the needle arm 116 above the puncture needle 122 and the vertical frame 114. The coiled portion may expand when the needle arm 116 rotates away from the vertical frame 114 and retract when the needle arm 116 rotates toward the vertical frame 114. The coiled portion of the fluid tube may be spiral, curved, or otherwise coiled to provide longitudinal expansion and contraction in a predictable manner that does not interfere with other movements of various components within the sample manager 14.

[0061] See again Figure 3 , needle arm 116 is shown in this view as having been rotated to a home position, whereby protruding stopper 182 connected to, coupled to, or integrated into vertical frame 114 contacts needle assembly 190. The home position may be a position where the needle arm 116 has been rotated to a stop point beyond which the needle arm 116 may not be able to rotate. As shown in the figure, in the home position, needle arm 116 has been rotated in a clockwise direction to a maximum rotation point, whereby needle arm 116 is stopped from further clockwise rotation by protruding stopper 182.

[0062] Attached to reference base 112 may be a needle cleaning system (not shown) extending from an opening 170 in reference base 112 located near the home position or location. The needle cleaning system may include a plurality of liquid source tubes, each configured to introduce water and / or other cleaning agents to clean introducer needle 122 and / or the introducer needle as the needle moves over the needle cleaning system. The cleaning process may include, for example, providing a first cleaning agent to introducer needle 122 from a first of the liquid source tubes, and then moving introducer needle 122 over a second of the liquid source tubes to be cleaned with water. Other cleaning processes and structures suitable for cleaning the needle in needle arm 116 are contemplated.

[0063] The needle arm 116 can be configured to rotate about the rotation axis 154 and the second axis A2 by an amount that allows the needle assembly 190 to completely cover the entire working portion of the sample disc 110. In the illustrated embodiment, the needle arm 116 can be configured to rotate more than 45 degrees but less than 90 degrees. Additional rotational motions (i.e., equal to or greater than 90 degrees) beyond those illustrated are also contemplated in other embodiments.

[0064] See also Figure 4 and Figure 5 , showing an embodiment according to Figure 1 and Figure 2 14, wherein the needle arm 116 is located in two calibration positions. In various contemplated embodiments, various calibration systems are contemplated. Figure 4 and Figure 5 An exemplary calibration system is shown in which the data system 34 and / or the sample manager control system can be configured to calibrate the sampling mechanism 100 for use. A calibration process may include, for example, Figure 4 The first step shown is to move the sample tray 110 and the needle arm 116 to align the needle with the first opening 210 in the sample tray, and then record the first encoder position of each of the sample tray 110 and the needle arm 116. For example, the needle arm 116 can be moved from an original position (such as Figure 3 Move counterclockwise to Figure 4 The position shown is such that the puncture needle 122 (or sample needle) is directly above the first opening 210 .

[0065] The calibration process may then include moving the sample tray 110 and needle arm 116 to Figure 5 The second step involves aligning the puncture needle 122 (or sample needle) with the second opening 220 in the sample tray. The calibration process can then include recording a second encoder position for each of the sample tray 110 and the needle arm 116. Using the known first and second encoder positions, the data system 34 and / or the sample manager control system can be configured to back-calculate the geometric parameters of the sampling mechanism 100, thereby calibrating the movement and position of the sample tray 110 and the needle arm 116. Positional accuracy can be more precise than typical prior art calibration processes because the inventive method described above does not rely on an assumed geometric quality within a certain level of tolerance.

[0066] Figure 6A perspective view of the needle arm 116 detached from the interior of the sample manager 14, according to one embodiment, is depicted. As shown, the needle arm 116 includes a base 230 that is removably attachable to the sample manager 14 of the liquid chromatography system 10. The needle arm 116 also includes a needle assembly 190 that is removably attached to the base 230. The removability of the base 230 from the sample manager 14 and the removability of the needle assembly 190 from the base 230 can each be provided by an accessible bolt, screw, pin, or other easily accessible, engageable, and / or releasable coupling device. The removable attachability of each of these components as described herein provides for ease of servicing and replacement of components of the needle arm 116 through the front door of the sample manager 14. In addition, as described above, the needle arm 116 includes sufficient structure to provide for rotational movement of the arm about a vertical axis when the needle arm 116 is attached to the sample manager 14.

[0067] Figure 7 Depicts a disassembled needle assembly 190 according to one embodiment. Figure 6 14. The base 230 includes a removable needle arm housing 158. The removable needle arm housing 158 provides a framework for attaching the base 230 to the interior of the sample manager 14 of the liquid chromatography system 10, such as by attaching the removable needle arm housing 158 to the vertical frame 114. The removable needle arm housing 158 includes a flat vertical surface that is configured to abut a flat vertical surface of the vertical frame 114. Figure 6 As shown, a plurality of alignment pins 234 located on the back surface of the needle arm housing 158 cooperate with the accessible bolts 162 to attach the flat vertical surface of the needle arm housing 158 to the flat vertical surface of the vertical frame 114. Although not shown, the vertical frame 114 may include corresponding holes or concave receiving openings for receiving each of the accessible bolts 162 and the alignment pins 234.

[0068] As shown, the base 230 includes a shaft 154 configured to rotate about a vertical axis A2. The removable needle arm housing 158 is configured to hold the shaft 154 in both a top position and a bottom position while allowing the shaft 154 to rotate about the removable needle arm housing 158. Specifically, the removable needle arm housing 158 includes a lower horizontal plate 160 and an upper horizontal plate 161 extending from a flat vertical surface of the removable needle arm housing 158. The bushing 156 is provided with an opening at the lower horizontal plate 160 to allow the shaft 154 to rotate therein.

[0069] The base 230 also includes a motor 144, a drive mechanism 142, a belt 148, a pulley 152, and a rotating plate 155. The drive mechanism 142 of the motor 144 can be a drive shaft, etc., which the motor 144 is configured to rotate. The rotation of the drive mechanism 142 further causes the belt 148 to move, thereby causing the pulley 152 to rotate. The pulley is attached to the vertical shaft 154. The rotating plate 155 is attached to the shaft 154 and is configured to rotate as the shaft 154 rotates.

[0070] Figure 8 Depicted is a side view of the needle arm 116 including both the needle assembly 190 and the base 230 according to one embodiment. Figure 6 Perspective drawing and Figure 8 , showing a side view of the base 230, which includes each of the motor 144, the magnetic encoder 146, the housing 158, and the rotating plate 155. The needle assembly 190 includes a housing 264 or other body to which the components of the needle assembly 190 are attached. As shown, the plate 192 of the housing 264 of the needle assembly 190 is attached to the base 230, and specifically to the rotating plate 155.

[0071] Needle assembly 190 includes a drive system. The drive system includes a first motor having a first drive shaft 236 attached to the top of plate 192 of housing 264. Needle assembly 190 also includes a second motor 164b having a second drive shaft 238 attached to the bottom of plate 192 of housing 264. First motor 164a and first drive shaft 236 are configured to impart vertical motion or movement to introducer needle 122 by imparting vertical motion or movement to introducer needle axis 260. Similarly, second motor 164b and second drive shaft 238 are configured to impart vertical motion or movement to sample needle 261 by imparting vertical motion or movement to sample needle axis 258.

[0072] Furthermore, stripper foot 262 is attached to a stripper foot axis 268, which includes a spring-loaded end 266 having a spring mechanism. The spring mechanism can be configured to compress during downward movement of stripper foot 262 and stripper foot axis 268. In use, stripper foot 262 can contact the top of a sample vial (not shown), after which puncture needle 122 can be pushed through the sample vial's protective membrane. After puncturing needle 122 has punctured this top protective membrane, puncture needle 122 must be retracted from the sample vial and the protective membrane. Stripper foot 262 can be configured to provide a downward force on the top of the sample vial, allowing puncture needle 122 to properly retract without adhering to the sample vial's protective membrane. Stripper foot 262 includes an opening through which puncture needle 122 is configured to extend during puncture.

[0073] like Figure 6 As shown, the stripper leg axis 268 is movable relative to the puncture needle axis 260 via two couplings 270. The couplings 270 may include top and bottom elongated vertical openings in the stripper leg axis 268, through which respective top and bottom pins extend. The respective top and bottom pins are attached to a puncture needle coupling surface 272 of the puncture needle axis 260. The top and bottom elongated vertical openings cooperate with the pins to connect or otherwise couple the stripper leg axis 268 and the puncture needle axis 260 in a manner that allows vertical movement between the stripper leg axis 268 and the puncture needle axis 260. The maximum vertical movement between the stripper leg axis 268 and the puncture needle axis 260 is limited by the vertical lengths of the top and bottom elongated vertical openings in the stripper leg axis 268.

[0074] The sample needle 261 is positioned along the same vertical axis as the puncture needle 122. The sample needle 261 can be a needle having a smaller diameter than the puncture needle 122, such that the sample needle 261 is configured to extend through the larger diameter opening of the puncture needle 122. The needle holder 244 is located at the top of the sample needle axis 258. The sample needle holder 244 can be configured to removably receive the sample needle 261 in a position that aligns the sample needle 261 with the puncture needle 122. The sample needle holder 244 is attached to the sample needle axis 258 so that the sample needle holder 244 and, thereby, the sample needle 261 moves when the sample needle axis 258 is driven or moved by the second motor 164b and its second drive shaft 238.

[0075] Figure 9 A top view of the needle arm 116 is depicted according to one embodiment. Figure 6 Perspective drawing and Figure 9 , and a top view of the needle arm 116. The sensor system includes a sample needle origin sensor 240, a puncture needle origin sensor 254, and a top sensor 252. The sensor system may also include a printed circuit board 246 configured to provide power, control signals, and / or communication signals to / from the various sensors 240, 254, 252 in the sensor system. The printed circuit board 246 may be a flexible circuit board configured to flex with rotation of the needle assembly 190 about the vertical axis 154. The printed circuit board 246 may be able to perform its functions without losing its signal and / or conductive integrity while flexing back and forth throughout the life cycle of the needle arm 116 due to rotation of the needle assembly 190 about the vertical axis 154. The sensor system and / or the printed circuit board 246 and sensors 240, 254, 252 may be in operable communication with a control system, such as a data system 34, so that sensed information is provided to the data system 34 for processing.

[0076] The sample needle origin sensor 240 is configured to sense movement of the sample needle axis 258 and / or determine when the sample needle axis 258 reaches its home (top) position. The sample needle origin sensor 240 can be configured to sense and / or determine that the sample needle 261 has moved a predetermined distance in the vertical direction to the sample needle home position. The sample needle holder 244 is connected to the sample needle axis 258 and moves with the sample needle axis 258. The sample needle holder 244 includes an extension protrusion 242 configured to move between the two prongs of the sample needle origin sensor 240. Therefore, when the sample needle axis 258 moves to the top home position, the extension protrusion 242 is positioned between the two prongs of the sample needle origin sensor 240, thereby sensing that the sample needle axis 258 is in the home position. A connecting conductor 248 extends between the printed circuit board 246 and the sample needle origin sensor 240, which is configured to provide power and / or other control or communication signals to and from the sample needle origin sensor 240.

[0077] Needle origin sensor 254 is configured to sense movement of needle axis 260 and / or determine when needle axis 260 reaches its home (top) position. Needle origin sensor 254 can be configured to sense and / or determine that needle 122 has moved a predetermined distance in the vertical direction to the home position. Needle axis 260, and specifically its needle coupling surface 272, includes an extension protrusion 256 configured to move between the two prongs of needle origin sensor 254. Thus, when needle axis 260 moves to the top home position, extension protrusion 256 is positioned between the two prongs of needle origin sensor 254, thereby sensing that needle axis 260 is in the home position. Connecting conductor 248 extends between printed circuit board 246 and needle origin sensor 254, which is configured to provide power and / or other control or communication signals to and from needle origin sensor 254.

[0078] The top sensor 252 of the sensor system is configured to sense when the stripper leg 262 is compressed by a predetermined amount. This predetermined amount can correspond to the force acting on the stripper leg 262 through the top of the sample bottle. A service loop 250 can extend from the printed circuit board 246 to the top sensor 252 to provide power and / or other control signals or communication signals to and from the top sensor 252. The top sensor 252 can be a stripper leg movement sensor configured to determine that the stripper leg 262 has moved a predetermined distance in a vertical direction.

[0079] Figure 10 Depicted is a method for Figure 910. A side cross-sectional view of the needle arm 116 is shown as taken at arrow 10-10 in FIG. As shown, the drive system can include a system for converting the rotational motion of the drive shafts 236, 238 into vertical linear motion of the axes 258, 260. The first motor 164a and the second motor 164b can be operated independently of each other, so that the puncture needle 122 and the sample needle 261 can move vertically independently. The top drive shaft 236 is shown as extending from the first motor 164a through an opening in the plate 192 of the housing 264. Similarly, the bottom drive shaft 238 is shown as extending from the second motor 164b through an opening in the plate 192 of the housing 264. As shown, the top drive shaft 236 is attached to a coupling structure 274, which is configured to pass around the sample needle axis 258 and engage with the puncture needle axis 260 to convert the rotational motion of the drive shaft 236 into linear vertical motion of the puncture needle axis 260. Similarly, the bottom drive shaft 238 is attached to an engagement structure 276 that is configured to engage with the sample needle axis 258 to convert the rotational motion of the drive shaft 238 into linear vertical motion of the sample needle axis 258.

[0080] While the present invention has been shown and described with reference to particular embodiments, it will be understood by those skilled in the art that various changes in form and details may be made without departing from the spirit and scope of the invention as described in the following claims.

Claims

1. A liquid chromatography system, comprising: solvent delivery systems; A sample manager having a thermal processing chamber comprising: A sampling mechanism is installed in the heat treatment chamber, and the sampling mechanism includes: Sample tray; A needle driver, comprising: a base comprising a shaft configured to rotate about a vertical axis, the base attachable to an interior of a sample manager of a liquid chromatography system; a needle assembly attached to the base, the needle assembly including a sample needle; and a drive system attached to the base, the drive system comprising a sample needle motor configured to impart vertical movement on the sample needle; and a sample delivery system in fluid communication with the solvent delivery system, the sample delivery system being configured to transfer a first sample from a first sample vial holder positioned in the sample tray into a chromatographic flow stream; a liquid chromatography column located downstream of the solvent delivery system and the sample delivery system; and a detector located downstream of the liquid chromatography column, wherein rotation of the shaft about the vertical axis rotates the needle assembly and the sample needle motor about the vertical axis, said rotation combined with rotation of the sample tray to facilitate providing complete coverage of a first sample vial holder located in the sample tray, and wherein the needle assembly is attachably removable from the base of the needle driver using a plurality of accessible bolts, wherein the sample manager further comprises a door that provides a technician with access to the thermal processing chamber when opened, and wherein the needle driver is removable from the thermal processing chamber through the door.

2. The liquid chromatography system of claim 1 , wherein the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor, the puncture needle motor being configured to impart vertical movement on the puncture needle independently of the vertical movement of the sample needle, and wherein the needle assembly further comprises a stripper foot movable in the vertical direction, wherein the stripper foot comprises an opening, the puncture needle being configured to extend through the opening during puncture.

3. The liquid chromatography system of claim 2 , wherein the needle driver further comprises a sensor system comprising a flexible circuit board attached to the base and configured to flex as the shaft rotates about the vertical axis, the sensor system further comprising: a stripper leg movement sensor configured to determine that the stripper leg has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved vertically to the sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved vertically to the puncture needle original position.

4. The liquid chromatography system according to claim 1 , wherein the needle driver further comprises: a shaft motor configured to rotate the shaft about the vertical axis; as well as A magnetic encoder is configured to maintain a precise rotational position of the shaft of the base.

5. A liquid chromatography system according to claim 1, wherein the base of the needle drive further comprises a needle arm housing, the needle arm housing supporting the shaft at at least two locations, the needle arm housing being attached to the interior of the thermal processing chamber of the sample manager using a plurality of accessible bolts.

6. A liquid chromatography sample manager, comprising: heat treatment chamber; a sample tray, the sample tray being installed in the heat treatment chamber; A needle driver, comprising: a base comprising a shaft configured to rotate about a vertical axis, the base attachable to an interior of a sample manager of a liquid chromatography system; a needle assembly attached to the base, the needle assembly including a sample needle; and a drive system attached to the base, the drive system comprising a sample needle motor configured to impart vertical movement on the sample needle; and a sample delivery system configured to transfer a first sample from a first sample vial holder located in the sample tray into a chromatographic flow stream, wherein rotation of the shaft about the vertical axis rotates the needle assembly and the sample needle motor about the vertical axis, said rotation combined with rotation of the sample tray to facilitate providing complete coverage of a first sample vial holder located in the sample tray, and wherein the needle assembly is attachably removable from the base of the needle driver using a plurality of accessible bolts, wherein the liquid chromatography sample manager further comprises a door that, when opened, provides a technician with access to the thermal processing chamber, wherein the needle driver is removable from the thermal processing chamber through the door.

7. The liquid chromatography sample manager of claim 6 , wherein the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor, the puncture needle motor being configured to impart vertical movement on the puncture needle independently of the vertical movement of the sample needle, and wherein the needle assembly further comprises a stripper foot movable in the vertical direction, wherein the stripper foot comprises an opening, the puncture needle being configured to extend through the opening during puncture.

8. The liquid chromatography sample manager of claim 6, the needle driver further comprising a sensor system comprising a flexible circuit board attached to the base and configured to flex as the shaft rotates about the vertical axis, the sensor system further comprising: a stripper leg movement sensor configured to determine that the stripper leg has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved vertically to the sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved vertically to the puncture needle original position.

9. The liquid chromatography sample manager according to claim 6, wherein the needle driver further comprises: a shaft motor configured to rotate the shaft about the vertical axis; as well as A magnetic encoder is configured to maintain a precise rotational position of the shaft of the base.

10. The liquid chromatography sample manager of claim 6, wherein the base of the needle drive further comprises a needle arm housing that supports the shaft at at least two locations, the needle arm housing being attached to the interior of the thermal processing chamber of the sample manager using a plurality of accessible bolts.

11. A needle driver for a liquid chromatography system, the needle driver comprising: a base comprising a shaft configured to rotate about a vertical axis, the base attachable to an interior of a sample manager of a liquid chromatography system; a needle assembly attached to the base, the needle assembly comprising a sample needle; as well as a drive system attached to the base, the drive system comprising a sample needle motor configured to impart vertical movement on the sample needle, wherein rotation of the shaft about the vertical axis rotates the needle assembly and the sample needle motor about the vertical axis, said rotation combined with rotation of the sample tray to facilitate providing complete coverage of a first sample vial holder located in the sample tray, and wherein the needle assembly is attachably removable from a base of the needle driver using a plurality of accessible bolts.

12. A needle driver according to claim 11, wherein the needle assembly further comprises a puncture needle, and wherein the drive system further comprises a puncture needle motor, the puncture needle motor being configured to impart vertical movement on the puncture needle independently of the vertical movement of the sample needle.

13. The needle driver of claim 12, wherein the needle assembly further comprises a stripper foot movable in the vertical direction, wherein the stripper foot comprises an opening, the puncture needle being configured to extend through the opening during puncture.

14. The needle driver of claim 13, further comprising a sensor system comprising a flexible circuit board attached to the base and configured to flex with the rotation of the shaft about the vertical axis.

15. The needle driver of claim 14, the sensor system further comprising: a stripper leg movement sensor configured to determine that the stripper leg has moved a predetermined distance in a vertical direction; a sample needle movement sensor configured to determine that the sample needle has moved vertically to the sample needle original position; and a puncture needle movement sensor configured to determine that the puncture needle has moved vertically to the puncture needle original position.

16. The needle driver of claim 11, further comprising a spindle motor configured to rotate the spindle about the vertical axis.

17. The needle driver of claim 16, further comprising a magnetic encoder configured to maintain a precise rotational position of the shaft of the base.

18. The needle driver of claim 11 , wherein the base further comprises a needle arm housing that supports the shaft at at least two locations, the needle arm housing being attachable to the interior of the sample manager of the liquid chromatography system using a plurality of accessible bolts.

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