Patent Publication Number: US-11656208-B2

Title: Multi-injection mode valve module

Description:
RELATED APPLICATIONS 
     This application claims priority to U.S. Provisional Application Ser. No. 62/140,615, filed on Mar. 31, 2015 entitled “MULTI-INJECTION MODE VALVE MODULE”, and International Patent Application No. PCT/US2016/018218 filed on Feb. 17, 2016 entitled “MULTI-INJECTION MODE VALVE MODULE”, and is a continuation application of U.S. Nonprovisional application Ser. No. 15/559,276, issued as U.S. Pat. No. 10,955,391, entitled “MULTI-INJECTION MODE VALVE MODULE”, the entireties of which are incorporated by reference herein. 
    
    
     FIELD OF THE INVENTION 
     The invention relates generally to chromatography systems. More specifically, the invention relates to valve modules used to add volume selectively and automatically to a chromatography system. 
     BACKGROUND 
     Chromatography is a set of techniques for separating a mixture into its constituents. Generally, in a liquid chromatography analysis, a pump system takes in and delivers a mixture of liquid solvents (and/or other fluids) to a sample manager, where a sample is injected into the solvent stream. The sample is the material under analysis. Examples of samples include, but are not limited to, complex mixtures of proteins, protein precursors, protein fragments, reaction products, and other compounds. The mobile phase comprised of a sample with the mixture of solvents (and/or other fluids), moves to a point of use, such as a separation column, referred to as the stationary phase. By passing the mobile phase through the column, the various components in the sample separate from each other at different rates and thus elute from the column at different times. A detector may receive the separated components from the column and produce an output from which the identity and quantity of the analytes may be determined. 
     Important to the successful performance of a chromatography system by such entities, for example, as pharmaceutical laboratories, companies, and other facilities, is ensuring the chromatography system is qualified for use in regulated environments. Various national and international regulations, quality standards, and company policies require the qualification of the analytical instruments involved in the chromatographic separations. Qualification pertains to instruments, ranging from individual modules and to complete chromatography systems (i.e., pump, sample injector, column module, and detector). A qualification may be performed initially, before use of a chromatography system, to establish a baseline and to determine if performance falls within predefined specifications, and, then regularly thereafter, to ensure the chromatography system remains within specification. 
     Full system qualifications generally test a chromatography system in a manner that the chromatography system is expected to be used. A variant of full system qualification is to qualify unique aspects of each configuration. For example, in high sample dispersion mode, system precision, injector linearity, and carryover require verification. The same metrics require verification for a low sample dispersion mode. 
     Manually changing the system mixing volume or the sample dispersion of a liquid chromatography (LC) system is a common practice used to accommodate the needs of a particular LC separation. Such manual alterations, however, can invalidate the qualification of the LC system, thereby requiring a time-consuming requalification before the altered LC system can be used. 
     SUMMARY 
     All examples and features mentioned below can be combined in any technically possible way. 
     In one aspect, a chromatography system with an associated system volume and a sample dispersion volume comprises a pump pumping a flow of gradient, a sample manager for introducing a sample to the flow of gradient, and a valve manager fluidically coupled to the pump and to the sample manager. The valve manager includes at least one valve. A first valve of the at least one valve has a plurality of ports including an inlet port that receives the flow of gradient from the pump and an outlet port through which the flow of gradient exits the first valve. The first valve has at least two different, automatically selectable positions. A first position of the at least two different automatically selectable positions of the first valve operates to change one of the system and sample dispersion volumes of the chromatography system when the first valve is automatically switched into the first position. 
     Embodiments of the chromatography system may include one of the following features, or any combination thereof. 
     The chromatography system may further comprise a valve drive operatively coupled to the first valve, and a processor in communication with the valve drive. The processor is programmed to qualify the chromatography system with the first valve in the first position, to operate the valve drive to switch the first valve automatically from the first position into a second position of the at least two different automatically selectable positions, and to qualify the chromatography system with the first valve in the second position. 
     The valve manager may further include at least one mixer. A first mixer of the at least one mixer may be connected between a third port and a fourth port of the first valve. The first position of the at least two different automatically selectable positions of the first valve places the first mixer of the at least one mixer into a path of the flow of gradient from the pump to change the system volume of the chromatography system. A volume of the first mixer may be predetermined to increase the system volume of the chromatography system to match a system volume of another model of chromatography system. A second mixer may be disposed in the path of the flow of gradient between the pump and the first valve. Alternatively, a second mixer of the at least one mixer may be connected between a fifth port and a sixth port of the first valve. A second position of the at least two different positions of the first valve places the second mixer of the at least one mixer into the path of the flow of gradient from the pump, while removing the first mixer from the path. 
     In other embodiments of the chromatography system, the pump may comprises the first valve, or the first valve may include seven ports, or the sample manager may include a flow-through needle with a tip and a proximal end opposite the tip, wherein the first position of the at least two different automatically selectable positions of the first valve operates to change the sample dispersion volume of the chromatography system by directing the flow of gradient in a reverse direction through the sample manager such that the flow of gradient enters the flow-through needle through the tip. 
     In another embodiment, the valve manager may further include at least one mixer. A first mixer of the at least one mixer is connected between a third port and a fourth port of the first valve. The first position of the at least two different automatically selectable positions of the first valve places the first mixer of the at least one mixer into a path of flow of sample composition between the sample manager and a column manager to increase the sample dispersion volume of the chromatography system. The at least one mixer may include a second mixer connected between a fifth port and a sixth port of the first valve. A second position of the at least two different automatically selectable positions of the first valve places the second mixer into the path of the flow of sample composition between the sample manager and a column manager, while removing the first mixer from the path of the flow of sample composition between the sample manager and the column manager. 
     The chromatography system may further comprise a column manager. The at least one valve of the valve manager may include a second valve. The second valve has a plurality of ports including an inlet port connected to the sample manager for receiving a flow of sample composition therefrom and an outlet port fludically coupled to the column manager for passing the flow of sample composition thereto. The sample manager may include a flow-through needle with a tip and a proximal end opposite the tip. The second valve may have a second inlet port connected to the outlet port of the first valve for receiving the flow of gradient therefrom. The second valve has at least two different automatically selectable positions. A first position of the at least two different positions of the second valve directs the flow of gradient through the sample manager in a forward direction such that the flow of gradient enters the flow-through needle through the proximal end and a second position of the at least two different positions of the second valve directs the flow of gradient through the sample manager in a reverse direction such that the flow of gradient enters the flow-through needle through the tip. The valve manager may further include a first mixer of the at least one mixer being connected between a third port and a fourth port of the first valve and a second mixer connected between a fifth port and a sixth port of the first valve. A second position of the at least two different automatically selectable positions of the first valve places the second mixer into the path of the flow of gradient from the pump, while bypassing the first mixer. 
     In one embodiment, the sample manager may include a flow-through needle with a tip and a proximal end opposite the tip. The second valve may have a second inlet port connected to the outlet port of the first valve for receiving the flow of gradient therefrom. Also, the second valve may have at least two different automatically selectable positions. A first position of the at least two different positions of the second valve directs the flow of gradient through the sample manager in a forward direction such that the flow of gradient enters the flow-through needle through the proximal end and a second position of the at least two different positions of the second valve directs the flow of gradient through the sample manager in a reverse direction such that the flow of gradient enters the flow-through needle through the tip. 
     In another embodiment, the outlet port of the first valve is fludically coupled to the sample manager for passing the flow of gradient thereto. In this embodiment, the chromatography system may further comprise a first mixer connected between a third port and a fourth port of the first valve, a second mixer connected between a fifth port and a sixth port of the first valve, wherein a second position of the at least two different automatically selectable positions of the first valve places the second mixer into the path of the flow of gradient from the pump, while removing the first mixer from the path, and a third mixer connected between a first port and a second port of the second valve. The second valve has at least two different automatically selectable positions. A first position of the at least two different automatically selectable positions of the second valve places the third mixer in a path of the flow of sample composition between the sample manager and the column manager. 
     In addition, the chromatography system may further comprise a fourth mixer connected between a third port and a fourth port of the second valve, wherein a second position of the at least two different automatically selectable positions of the second valve places the fourth mixer into the path of the flow of sample composition between the sample manager and the column manager, while removing the third mixer from the path of the flow of sample composition between the sample manager and the column manager. 
     In another aspect, a valve module used in chromatography comprises at least one rotary valve. A first rotary valve of the at least one rotary valve has a plurality of ports including an inlet port for receiving a flow of gradient and an outlet port through which the flow of gradient exits the first rotary valve. The first rotary valve has at least two different automatically selectable positions. The valve module further comprises at least one mixer including a first mixer connected between a third port and a fourth port of the first rotary valve, and a valve drive operatively coupled to the first rotary valve and responsive to a control command from a processor to switch the first rotary valve automatically into the first position of the at least two different automatically selectable positions to place the first mixer into a path of the flow of gradient. 
     Embodiments of the valve module may include one of the following features, or any combination thereof. 
     The first valve may include seven ports. 
     The valve module may further comprise a second mixer of the at least one mixer connected between a fifth port and a sixth port of the first rotary valve. A second position of the at least two different positions of the first rotary valve places the second mixer of the at least one mixer into the path of the flow of gradient from the pump, while removing the first mixer from the path. The at least one rotary valve may include a second rotary valve. The second rotary valve has a plurality of ports including an inlet port for receiving a flow of sample composition from a sample manager and an outlet port fludically coupled to a column manager for passing the flow of sample composition thereto. The second rotary valve may have a second inlet port connected to the outlet port of the first rotary valve for receiving the flow of gradient therefrom. The second rotary valve has at least two different positions. A first position of the at least two different positions of the second valve is for directing the flow of gradient through the sample manager in a forward direction and a second position of the at least two different positions of the second valve is for directing the flow of gradient through the sample manager in a reverse direction. 
     In one embodiment, the valve module may further comprise a second mixer of the at least one mixer connected between a fifth port and a sixth port of the first rotary valve. A second position of the at least two different positions of the first rotary valve places the second mixer of the at least one mixer into the path of the flow of gradient from the pump, while removing the first mixer from the path. The second rotary valve may have a second inlet port connected to the outlet port of the first rotary valve for receiving the flow of gradient therefrom. The second rotary valve has at least two different positions. A first position of the at least two different positions of the second rotary valve is for directing the flow of gradient through the sample manager in a forward direction and a second position of the at least two different positions of the second valve is for directing the flow of gradient through the sample manager in a reverse direction. 
     In one embodiment, the outlet port of the first rotary valve may be fludically coupled to the sample manager for passing the flow of gradient thereto, and the valve module may further comprise a second mixer, of the at least one mixer, connected between a fifth port and a sixth port of the first rotary valve, wherein a second position of the at least two different positions of the first rotary valve places the second mixer of the at least one mixer into the path of the flow of gradient from the pump, while removing the first mixer from the path. In this embodiment, the valve module may further comprise a third mixer connected between a third port and a fourth port of the second rotary valve. The second valve has at least two different positions. A first position of the at least two different positions of the second valve places the third mixer in a path of the flow of sample composition between the sample manager and the column manager. In addition, a fourth mixer may be connected between a fifth port and a sixth port of the second rotary valve, wherein a second position of the at least two different positions of the second rotary valve places the fourth mixer into the path of the flow of sample composition between the sample manager and the column manager, while removing the third mixer from the path of the flow of sample composition between the sample manager and the column manager. 
     In still another aspect, a method is provided of running a liquid chromatography system having an associated system volume and a sample dispersion volume. The liquid chromatography system further has a valve manager fluidically coupled to a pumping system and a sample manager. The valve manager includes at least one valve. A first valve of the at least one valve has a plurality of ports including an inlet port that receives the flow of gradient from the pump and an outlet port through which the flow of gradient exits the first valve. The first valve has at least two different, automatically selectable positions. A first position of the at least two different automatically selectable positions of the first valve increases one of the system and sample dispersion volumes of the chromatography system. The method comprises qualifying the liquid chromatography system with the first valve in the first position of the at least two different automatically selectable positions, qualifying the liquid chromatography system with the first valve in the second position of the at least two different automatically selectable positions, performing a chromatographic run with the first valve of the valve manager in the first position, switching the first valve from the first position to the second position, and performing a chromatographic run with the first valve of the valve manager in the second position without having to requalify the liquid chromatography system. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above and further advantages of this invention may be better understood by referring to the following description in conjunction with the accompanying drawings, in which like numerals indicate like structural elements and features in various figures. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG.  1    is a diagram of an embodiment of a liquid chromatography (LC) system with a volume manager used to add volume selectively and automatically to the LC system without having to requalify the LC system. 
         FIG.  2    is a diagram of an embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, without requiring a subsequent requalification of the LC system as a result of the change, the valve manager being in a first selectable configuration in communication with an embodiment of a sample manager of the LC system. 
         FIG.  3    is a diagram of the valve manager of  FIG.  2    in communication with the sample manager, wherein the valve manager is in a second, selectable configuration that adds the volume of a mixer to the system volume of the LC system without requiring a subsequent requalification of the LC system as a result of the change. 
         FIG.  4    is a diagram of the valve manager of  FIG.  2    in communication with the sample manager of  FIG.  2   , wherein the valve manager is in a third, selectable configuration that increases a sample dispersion volume of the LC system by reversing the direction of gradient flow through the sample manager from the flow direction shown in  FIG.  2    and  FIG.  3   . 
         FIG.  5    is a diagram of the valve manager of  FIG.  2    in communication with the sample manager of  FIG.  2   , wherein the valve manager is in a fourth, selectable configuration that adds the volume of a mixer to the system volume of the LC system and increases a sample dispersion volume of the LC system by reversing the direction of gradient flow through the sample manager, such as described in connection with  FIG.  4   . 
         FIG.  6    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, without requiring a subsequent requalification of the LC system as a result of the change, the valve manager having two four-port valves, one of which determines whether a mixer is added to the flow path and the other determining a direction of flow through the sample manager. 
         FIG.  7    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, without requiring requalification of the LC system as a result of the change, the valve manager having a six-port valve and a four-port valve, the six-port valve determining which of two mixers is added to the flow path and the four-port valve determining a direction of flow through the sample manager. 
         FIG.  8    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, without requiring requalification of the LC system as a result of the change, the valve manager having two six-port valves, one of which determines which of two mixers is added to the flow path and the other determines a direction of flow through the sample manager. 
         FIG.  9    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, the valve manager having a six-port valve and a four-port valve, the four-port valve determining whether a mixer is added to the flow path and the six-port valve determining a direction of flow through the sample manager. 
         FIG.  10    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, the valve manager having two six-port valves, one of which determines which of two mixers is added to a flow path upstream of the sample manager and the other determines which of two mixers is added to the flow path downstream of the sample manager. 
         FIG.  11    is a diagram of another embodiment of a valve manager capable of automatically changing the system volume of the LC system, sample dispersion volume, or both, the valve manager having a six-port valve and a four-port valve, the six-port valve determining which of two mixers is added to a flow path upstream of the sample manager and the four-port valve determining whether a mixer is added to the flow path downstream of the sample manager. 
         FIG.  12    is a diagram of an embodiment of a pump valve capable of automatically changing the system volume of the LC system by adding a mixer to the flow path, the pump valve being positioned to bypass the mixer. 
         FIG.  13    is a diagram of the valve manager of  FIG.  12   , wherein the pump valve is positioned to add the mixer to the flow path. 
         FIG.  14    is a diagram of the valve manager of  FIG.  12   , wherein the pump valve is positioned to facilitate a leak test of the LC system. 
         FIG.  15    is a diagram of the valve manager of  FIG.  12   , wherein the pump valve is positioned to vent the LC system. 
         FIG.  16    is a diagram of another embodiment of a pump valve capable of automatically changing the system volume of the LC system by selectively adding one of two mixers to the flow path, the valve being positioned to add a first mixer to the flow path. 
         FIG.  17    is a diagram of the valve manager of  FIG.  16   , wherein the pump valve is positioned to add the other of the two mixers to the flow path. 
         FIG.  18    is a diagram of the valve manager of  FIG.  16   , wherein the pump valve is positioned to facilitate a leak test of the LC system. 
         FIG.  19    is a diagram of the valve manager of  FIG.  12   , wherein the pump valve is positioned to vent the LC system. 
         FIG.  20    is a flow chart of an embodiment of a process automatically changing the system volume of the LC system, sample dispersion volume, or both, without requiring a system requalification in response to the change. 
     
    
    
     DETAILED DESCRIPTION 
     Chromatography systems described herein use a valve manager (also, valve module) to enable a user to automate the changing of the system mixing volume, sample dispersion volume, or both, of a liquid chromatography (LC) system so the LC system can accommodate the particular needs of the chromatographic separation. As used herein, system mixing refers to mixing occurring downstream of the pump because of tubing, system components, and additional selectable volumes. System mixing volume (or simply system volume—also known as gradient delay volume and dwell volume) refers to the overall fluid volume of such tubing, system components, and additional selectable volumes, from where the eluents (i.e., by a gradient proportioning valve or mixing tee) are proportioned to the inlet of the column. Sample dispersion refers to the dispersion of the sample as the sample travels through the tubing and connectors on the path to the column. Sample dispersion volume, as used herein, refers to the overall fluid volume of tubing, system components (e.g., a flow-through needle), and additional selectable volumes, from where the sample is introduced to the gradient to the inlet of the column. 
     The configurability of the valve manager enables a user to select a configuration automatically that gives the LC system characteristics that closely match the characteristics of older chromatographic systems. This ability to configure a contemporary LC system in order to match the characteristics of an older (legacy) chromatographic system is key to enabling efficient methods of transfer of older separations and methods taken from pharmaceutical compendia to the contemporary LC system. One can then transfer a method from the legacy chromatographic system without having to make any changes to the programmed gradient (i.e., the software that programs the method running through the LC system). 
     In addition, the LC system can be fully qualified in each of the multiple configurations of the valve manager through any qualification software, such as Systems Qualification Technology (SQT), without any disconnection or reconnection of any components or tubing. Fully qualifying the system in each of the valve manager configurations through SQT enables the user to ensure that both legacy and contemporary separations can be successfully run on the same chromatograph, without requiring a requalifying of the LC system each time a switch is made between the two types of separations, such switching being made by virtue of changing the valve manager configuration. Because the characteristics of a legacy chromatographic system can be switched as part of an instrument method, such characteristics can be qualified as part of the automated portion of the SQT. 
     In brief overview, each embodiment of valve manager described herein has multiple configurations. The valve manager has one or two conventional valves configured for automated control of the system mixing volume, sample dispersion volume, or both. The user can change the effective system mixing volume and sample dispersion volume, independently of the other. 
     In an example embodiment of a valve manager having two valves, the first of two valves is connected to the outlet of a pump and an inlet of the second valve, and an outlet of the second valve is connected to an inlet line and outlet line of the sample manager. The first valve can serve to introduce additional mixing volume to the outlet of the pump, thus changing the system mixing volume, while the second valve can determine a direction (forward or reverse) of the flow path through the sample manager, thus affecting the sample dispersion volume. Either valve can switch independently of the other, thus enabling the independent changes to the system mixing volume and sample dispersion volume. 
       FIG.  1    shows an embodiment of a liquid chromatography (LC) system  10  for separating a mixture into its constituents. Example implementations of the LC system include, but are not limited to, HPLC and UPLC systems. The chromatography system  10  includes a solvent delivery system  12  in fluidic communication with a valve manager (VM)  14  through tubing  16 . Generally, the solvent delivery system  12  includes pumps (not shown) in fluidic communication with solvent reservoirs  18  from which the pumps draw solvents. In one embodiment, the solvent delivery system  12  is a binary solvent manager (BSM), which uses two individual serial flow pumps to draw solvents from their reservoirs  18  and deliver a solvent composition to the VM  14 . An example implementation of a BSM is the ACQUITY® UPLC Binary Solvent Manager, manufactured by Waters Corp. of Milford, Mass. The pumps of the BSM are capable of generating pressure as high as 18K psi (pounds per square inch). Hereafter, for purposes of illustration by example, the solvent delivery system  12  may be referred to as a BSM  12  or LC pump  12 . 
     The VM  14  is in fluidic communication with a sample manager (SM)  20  by tubing  22  and  24  to enable the adding of volume to the chromatography system  10  without having to requalify the system configuration, as described in more detail later. Solvent composition (or gradient) arriving from the BSM  12  through tubing  16  passes through the VM  14  to the SM  20  by tubing  22 . Tubing  24  carries the solvent composition with the injected sample (i.e., mobile phase or sample composition) from the SM  20  to the VM  14 . The VM  14  is also in fluidic communication with a column manager (CM)  26  by tubing  28  by which the solvent composition with the injected sample passes to a column (not shown). Implementation of the VM  14  may be at the BSM  12 ; that is, the BSM  12  conventionally has a vent valve that is replaced with the VM  14  (or just the first valve  40  ( FIG.  2   ) of the VM  14 ). Except for changes to the plumbing, the VM  14  can reuse the valve drive previously used to operate the vent valve. 
     The SM  20  is in fluidic communication with a sample source  30  from which the SM  20  acquires a sample. The sample source  30  can be, for example, a vial containing the sample, or a process line, from which the sample manager  20  acquires and introduces a sample to the solvent composition arriving from the valve manager  14 . An example implementation of the sample manager  20  is the ACQUITY® FTN Sample Manager, manufactured by Waters Corp. of Milford, Mass. 
     The CM  26  generally provides a controlled temperature environment for one or more chromatography separation columns used in separating sample-solvent compositions. Each separation column is adapted to separate the various components (or analytes) of the sample from each other as the mobile passes through, and to elute the analytes (still carried by the mobile phase) from the column at different times. From the column manager  26 , the constituents of the separated sample pass to a detector  32  or other equipment, for example, a mass spectrometer or a Flame Ionization Detector (FID), for analyzing the separation. 
     The chromatography system  10  further includes a data system  34  that is in signal communication with the BSM  12 , the VM  14 , column manager  26 , detector  32 , and the SM  20 . The data system  34  has a processor and a switch (e.g., an Ethernet switch) for handling signal communication among the BSM  12 , the VM  14 , and SM  20 . In addition, the processor of the data system  34  is programmed to implement the various phases of operation performed by the VM (controlling a valve drive to rotate one or more valves) and the SM (e.g., turning pumps on and off, rotating a valve) in order to inject the sample to a solvent composition stream, as described herein. In addition, a host computing system  36  is in communication with the data system  34 , by which personnel can run qualifications of the LC system  10 , store results of the qualifications, and download various parameters and profiles to affect the data system&#39;s performance. For example, during a qualification of the LC system  10 , the data system  34  can automatically place the VM  14  in a first configuration, qualify the LC system with the VM  14  in that first configuration, change the VM  14  into a second configuration, and qualify the LC system with the VM  14  in that second configuration. The results of both qualifications can be stored in a database, and subsequently used to check the performance of the LC system. Further, subsequent automated switching of the VM  14  from the first configuration to the second configuration, or the second configuration to the first configuration, does not require a requalification of the LC system  10 . 
     The solvent delivery system  12 , VM  14 , SM  20 , CM  26 , detector  32 , and data system  34  may be separate instruments or integrated into a single unit. 
       FIG.  2    shows an embodiment the valve manager  14  in communication with an embodiment of the sample manager  20 . The VM  14  includes a first valve  40  in fluidic communication with a second valve  42 . Each valve  40 ,  42  is a rotary shear valve having a rotor fitted to a stator; the rotor rotates, while the stator is the stationary part of the valve. In general, the rotor has a plurality of arcuate flow-through channels or grooves circularly arranged in the rotor, and the stator has a plurality of stator ports symmetrically disposed around a radius of the stator. Each groove of the rotor connects two or more adjacent stator ports; which stator ports are actually connected to each other depends upon the position of the rotor. In general, the first valve  40  enables the addition of system volume to the LC system  10 ; the second valve  42  enables the addition of sample dispersion volume to the LC system  10  by changing the flow direction through the sample manager  20 . 
     The first valve  40  of the VM  14  has six stator ports  44 - 1 ,  44 - 2 ,  44 - 3 ,  44 - 4 ,  44 - 5 , and  44 - 6  (generally,  44 ) and three rotor channels  46 - 1 ,  46 - 2 , and  46 - 3  (generally,  46 ). In the configuration shown, rotor channel  46 - 1  connects stator ports  44 - 1  and  44 - 2 ; rotor channel  46 - 2  connects stator ports  44 - 3  and  44 - 4 ; and rotor channel  46 - 3  connects stator ports  44 - 5  and  44 - 6 . The stator port  44 - 4  is connected to the BSM  12 . Connected between stator ports  44 - 2  and  44 - 5  is a mixer  48 . 
     The second valve  42  of the VM  14  has four stator ports  50 - 1 ,  50 - 2 ,  50 - 3 , and  50 - 4 , (generally,  50 ) and two rotor channels  52 - 1  and  52 - 2  (generally,  52 ). In the configuration shown, rotor channel  52 - 1  connects stator ports  50 - 1  and  50 - 2  and rotor channel  52 - 2  connects stator ports  50 - 3  and  50 - 4 . Tubing  28  connects the stator port  50 - 2  to the column manager  26 ; and tubing  53  connects the stator port  50 - 4  to the stator port  44 - 3  of the first valve  40 . In general, the first valve  40  determines whether the volume of the mixer  48  is added to the system volume; whereas the second valve  42  determines the direction of gradient flow through the sample manager  20 . The direction of gradient flow through the sample manager  20  determines the sample injection dispersion. 
     Other embodiments of the valve manager  14  may have only one of the two valves, for example, only the first valve  40  or only the second valve  42 . Connected to each of the valves  40 ,  42  is a valve drive  45  for automatically rotating either or both valves under the control of the data system  34  ( FIG.  1   ). The valve drive  45  is omitted from the remainder of the FIGS. in this description to simplify the illustrations. 
     The SM  20  includes an injection valve  54 , a flow-through needle (FTN)  56 , a needle drive  58 , a seat  60 , a pressure source  62 , a transducer  64 , and a sample source  30  (here, e.g., a vial). 
     The injection valve  54  has six ports  66 - 1 ,  66 - 2 ,  66 - 3 ,  66 - 4 ,  66 - 5 , and  66 - 6  (generally,  66 ) and three rotor channels  68 - 1 ,  68 - 2 , and  68 - 3  (generally,  68 ). In the configuration shown, channel  68 - 1  connects stator ports  66 - 1  and  66 - 2 ; rotor channel  68 - 2  connects stator ports  66 - 3  and  66 - 4 ; and rotor channel  68 - 3  connects stator ports  66 - 5  and  66 - 6 . 
     The six ports  66  of the injection valve  54  are connected to the various components of the SM  20  and the second valve of the VM  14  as follows: tubing  70  connects port  66 - 1  to an exit port of the seat  60 ; tubing  22  ( FIG.  1   ) connects port  66 - 2  to the stator port  50 - 1  of the second valve  42  of the VM  14 ; tubing  24  ( FIG.  1   ) connects port  66 - 3  to the stator port  50 - 3  of the second valve  42  of the VM  14 ; tubing  76  connects port  66 - 4  to the entry end of the needle  56 ; tubing  78  connects port  66 - 5  to the transducer  64 ; and tubing  80  connects port  66 - 6  to waste. 
     In general, the needle  56  is part of the sample loop of the SM  20 ; the tubing  76 ,  70  and seat  60  complete the sample loop from port  66 - 4  to port  66 - 1 . The injection needle  56  has a tip that moves in and out of an injection port  82  of the seat  60  under the control of the needle drive  58 . The seat  60  produces a leak-proof seal when the needle tip enters therein. In addition to controlling the movement and position of the injection needle  56  (into and out of the injection port  82 ), the needle drive  58  can also move the injection needle  56  in an angular direction (theta motion) between the vial  30  and the injection port  82 . 
     The pressure source  62  produces a prescribed amount of pressure, which is measured by the transducer  64 . This pressure source  62  can be a unidirectional or bidirectional peristaltic pump or a milliGAT pump, or a syringe. 
     During operation of the LC system  10 , with the VM  14  in the configuration shown in  FIG.  2   , the BSM  12  pumps gradient into the stator port  44 - 4  of the first valve  40 . From the stator port  44 - 4 , the gradient passes through the rotor channel  46 - 2  and exits the first valve  40  through stator port  44 - 3 . Passing through tubing  53 , the gradient arrives at the stator port  50 - 4  of the second valve  42 . The gradient then passes through the rotor channel  52 - 2  to exit the second valve  42  through stator port  50 - 3 . From the stator port  50 - 3 , the gradient exits the second valve  42  and the valve manager  14  for delivery through tubing  24  to the stator port  66 - 3  of the valve  54  of the sample manager  20 . In this configuration, the volume of the mixer  48  is not in the flow path and, thus, not included in the system volume. 
     After entering the stator port  66 - 3  of the valve  54  of the sample manager  20 , the gradient passes through rotor channel  68 - 2  and exits the valve  54  through stator port  66 - 4 . The gradient then passes through tubing  76 , the flow-through needle  56 , the fluidic tee (seat  60 ), and the tubing  70  to return to the valve  54  at stator port  66 - 1 . When passing through the flow-through needle  56 , the gradient picks and moves a sample to become a sample composition. From the stator port  66 - 1 , the sample composition (or mobile phase) passes through the rotor channel  68 - 1  to exit the valve  54  through stator port  66 - 2 . Passing through tubing  22 , the sample composition arrives at stator port  50 - 1  of the second valve  42 . From the stator port  50 - 1 , the mobile phase passes through rotor channel  52 - 1  and exits the second valve  42  and valve manager  14  through the stator port  50 - 2  on the path through tubing  28  to the column manager  26 . 
       FIG.  3    shows a second configuration of the valve manager  14  in communication with the embodiment of the sample manager  20  of  FIG.  2   . The tubing connections between stator ports of the first and second valves  40 ,  42 , and between stator ports of the valve manager  14  and sample manager  20 , are the same as those described in  FIG.  2   . In this second configuration, the rotor of the first valve  40  of the valve manager  14  is turned, by one step, counterclockwise from the position shown in  FIG.  2   , so that the mixer  48  connected between stator ports  44 - 5  and  44 - 2  is added to the flow path of the gradient being pumped by the BSM  12 . (The rotor of the first valve  40  can turn clockwise by one step to achieve connections between the same pair of stator ports.) The flow path passes through the rotor channel  46 - 3  connecting stator ports  44 - 4  and  44 - 5 , the mixer  48 , and the rotor channel  46 - 2  connecting stator ports  44 - 2  and  44 - 3 . The rotor channel connections for the second valve  42  of the flow manager and injection valve  54  of the sample manager  20 , and the direction of fluidic flow through the second valve  42  and sample manager  20  towards the column manager  26  are unchanged from that shown in  FIG.  2   . 
     Accordingly, by automatically moving the first valve  40  into the position, as shown in  FIG.  3   , the volume of the mixer  48  becomes part of the overall system volume of the LC system  10 . A variety of commercially available mixers, having a range of mixing volumes, enables a technician to select a mixer of the desired volume when configuring the valve manager  14  (prior to qualification). The selected volume of the mixer  48  can then alter the system volume of the LC system  10  to match closely the system volume of a legacy LC system, thereby enabling methods previously performed on the legacy LC system to run unaltered on the LC system  10 . 
       FIG.  4    shows a third configuration of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . The tubing connections between stator ports of the first and second valves  40 ,  42 , and between stator ports of the valve manager  14  and sample manager  20 , are the same as those described in  FIG.  2   . In this configuration, the position of the first valve  40  matches the position of  FIG.  2   , whereas the rotor of the second valve  42  is turned, by one step, counterclockwise from its position shown in  FIG.  2    so that rotor channel  52 - 1  connects stator ports  50 - 4  and  50 - 1  and the rotor channel  52 - 2  connects stator ports  50 - 2  and  50 - 3 . (The rotor can turn clockwise by one step to achieve connections between the same pairs of stator ports.) During operation of the LC system  10  in the configuration shown in  FIG.  4   , the BSM  12  pumps gradient into the stator port  44 - 4  of the first valve  40 . From the stator port  44 - 4 , the gradient passes through the rotor channel  46 - 2  and exits the first valve  40  through stator port  44 - 3 . Passing through tubing  53 , the gradient arrives at the stator port  50 - 4  of the second valve  42 . Up to this point, the flow direction has been the same as that described in connection with  FIG.  2   , and the volume of the mixer  48  is not in the flow path and, thus, not included in the system volume. 
     From the stator port  50 - 4 , the gradient then passes through the rotor channel  52 - 1  to exit the second valve  42  through stator port  50 - 1 . From the stator port  50 - 1 , the gradient exits the second valve  42  and the valve manager  14  for delivery through tubing  22  to the stator port  66 - 2  of the valve  54  of the sample manager  20 . By entering the valve  54  through the stator port  66 - 2 , the direction of flow through the sample manager  20  is the reverse of the flow direction described in connection with  FIG.  2   . This reverse flow through the sample manager  20  increases the sample dispersion (i.e., the body of the flow-through needle  56  provides a greater volume within which the injected sample can mix than the volume of the tubing  70  in the forward direction). Advantageously, because both the forward and reverse flow configurations can be qualified automatically, switching between the two configurations does not require a time-consuming requalification. 
     Specifically, after entering the stator port  66 - 2  of the valve  54 , the gradient passes through rotor channel  68 - 1  and exits the valve  54  through stator port  66 - 1 . The gradient then passes through tubing  70 , the seat  60 , into the tip of the flow-through needle  56  (where it picks up the sample), and out through the tubing  76 , to return to the valve  54  at stator port  66 - 4 . 
     From the stator port  66 - 4 , the mobile phase with the sample (also referred to as the sample composition) passes through the rotor channel  68 - 2  to exit the sample manager valve  54  through the stator port  66 - 3 . Passing through tubing  24 , the sample composition arrives at stator port  50 - 3  of the second valve  42 . From the stator port  50 - 3 , the sample composition passes through rotor channel  52 - 2  and exits the second valve  42  (and valve manager  14 ) through the stator port  50 - 2 , onwards through tubing  28  to the column manager  26 . 
       FIG.  5    shows a fourth configuration of the valve manager  14  in communication with the sample manager of  FIG.  2   . The tubing connections between stator ports of the first and second valves  40 ,  42 , and between stator ports of the valve manager  14  and sample manager  20 , are the same as those described in  FIG.  2   . In this configuration, the position of the first valve  40  is the same as the position of the first valve  40  in  FIG.  3   , and the position of the second valve  42  is the same as the position of the first valve  40  in  FIG.  4   . In the fourth configuration, the first valve  40  places the mixer  48  in the path of the gradient flow, and the second valve  42  reverses the gradient flow through the sample manager  20 , as described in connection with  FIG.  4   . Accordingly, in comparison with the first configuration of  FIG.  2   , the fourth configuration enables the addition of system volume to the LC system  10  by virtue of switching the mixer  48  into to the flow path and to increase the sample dispersion volume by reversing the flow through the sample manager. 
       FIG.  6    shows a second embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . In this embodiment, the first valve  90  of the VM  14  is a four-port rotary valve, like the second valve  42 . The first valve  90  has four stator ports  92 - 1 ,  92 - 2 ,  92 - 3 , and  92 - 4  (generally,  92 ) and two rotor channels  94 - 1  and  94 - 2  (generally,  94 ). Rotor channel  94 - 1  connects stator ports  92 - 1  and  92 - 2 ; and rotor channel  94 - 2  connects stator ports  92 - 3  and  92 - 4 . The stator port  92 - 4  is connected to the BSM  12 . Connected between stator ports  92 - 1  and  92 - 2  is a mixer  96 . 
     The second valve  42  of the VM  14  and the sample manager  20 , and the stator port connections therebetween, are the same as those described in connection with  FIG.  2   . Tubing  98  connects the stator port  50 - 4  of the second valve  42  to the stator port  92 - 3  of the first valve  90 . 
     The valve manager  14  in  FIG.  6    is in a first configuration, wherein the first valve  90  bypasses the mixer  96  and the second valve  42  establishes a forward direction gradient flow through the sample manager  20 . 
     During operation of the LC system  10  in the configuration shown in  FIG.  6   , the BSM  12  pumps gradient into the stator port  92 - 4  of the first valve  90 . From the stator port  92 - 4 , the gradient passes through the rotor channel  94 - 2  and exits the first valve  90  through stator port  92 - 3 . Passing through tubing  98 , the gradient arrives at the stator port  50 - 4  of the second valve  42 . The gradient then passes through the rotor channel  52 - 2  to exit the second valve  42  through stator port  50 - 3 . From the stator port  50 - 3 , the gradient exits the second valve  42  and the valve manager  14  for delivery through tubing  24  to the stator port  66 - 3  of the injection valve  54  of the sample manager  20 . The gradient then passes through the sample manager  20  in the forward direction, as described in connection with  FIG.  2   , entering a proximal end (opposite the tip) of the flow-through needle  56 , where it picks up a sample, and returns to the second valve  42  through stator port  50 - 1 . From the stator port  50 - 1 , the sample composition passes through rotor channel  52 - 1  and exits the second valve  42  and the valve manager  14  through the stator port  50 - 2  on the path through tubing  28  to the column manager  26 . 
     In a second configuration of the valve manager  14  of  FIG.  6   , the position of the first valve  90  places the mixer  96  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  42  establishes a forward direction flow through the sample manager  20 . 
     In a third configuration of the valve manager  14 , the position of the first valve  90  causes the gradient flow coming from the BSM  12  to bypass the mixer  96  (like the first configuration), and the position of the second valve  42  establishes a reverse direction flow through the sample manager  20  (like the third configuration described in  FIG.  4   ). 
     In a fourth configuration of the valve manager  14 , the position of the first valve  90  places the mixer  96  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  42  establishes a reverse direction flow through the sample manager  20 . 
       FIG.  7    shows a third embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . This embodiment is the same as the embodiment of the valve manager  14  in  FIG.  2   , except for the particular placement of the mixer  48  and the addition of a second mixer  100 . In this embodiment, the mixer  48  is disposed between the stator ports  44 - 1  and  44 - 6  (in  FIG.  2   , it was between stator ports  44 - 2  and  44 - 5 ). The additional mixer  100  is disposed between stator ports  44 - 3  and  44 - 4 . Some tubing connections are also different from those in  FIG.  2   : the BSM  12  is connected to the stator port  44 - 5  of the first valve  40 ; and the tubing  53  connects the stator port  44 - 2  of the first valve  40  to the stator port  50 - 4  of the second valve  42  (in  FIG.  2   , stator ports  44 - 3  is connected to stator port  50 - 4 ). The stator port connections between the second valve  42  of the VM  14  and the sample manager  20  are the same as those described in connection with  FIG.  2   . 
     The first valve  40  determines which of the two mixers  48 ,  100  is placed in the path of the gradient flowing from the BSM  12 . The two mixers  48 ,  100  provide different volumes that can be selectively added to the system volume. The second valve  42  determines the flow direction, forward or reverse, through the sample manager  20 . 
     As shown in  FIG.  7   , the valve manager  14  is in a first configuration where the position of the first valve  40  places the mixer  48  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  42  establishes a forward direction flow through the sample manager  20 . 
     In a second configuration of the valve manager  14  of  FIG.  7   , the position of the first valve  40  places the other mixer  100  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  42  establishes a forward direction flow through the sample manager  20 . 
     In a third configuration of the valve manager  14 , the position of the first valve  40  places the mixer  48  into the path of the gradient flow coming from the BSM  12 , while the position of the second valve  42  establishes a reverse direction flow through the sample manager  20 . 
     In a fourth configuration of the valve manager  14 , the position of the first valve  40  places the other mixer  100  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  42  establishes a reverse direction flow through the sample manager  20 . 
     Advantageously, each of these configurations can be initially qualified and, therefore, any change in selection among the four configurations does not require a subsequent requalification as a result of the change. 
       FIG.  8    shows a fourth embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . In this embodiment, the sample manager  20  and the first valve  40  of the VM  14 , including the two mixers  48 ,  100 , are the same as the sample manager  20  and first valve  40  described in connection with  FIG.  7   , and the second valve  110  of the VM  14  is a six-port rotary valve, like the first valve  40 . The BSM  12  is connected to the stator port  44 - 5  of the first valve  40 . 
     The second valve  110  has six stator ports  112 - 1 ,  112 - 2 ,  112 - 3 ,  112 - 4 ,  112 - 5 , and  112 - 6  (generally,  112 ) and three rotor channels  114 - 1 ,  114 - 2 , and  114 - 3  (generally,  114 ). Rotor channel  114 - 1  connects stator ports  112 - 1  and  112 - 2 ; rotor channel  114 - 2  connects stator ports  112 - 3  and  112 - 4 ; and rotor channel  114 - 3  connects stator ports  112 - 5  and  112 - 6 . Stator port  112 - 1  is connected to stator port  112 - 2  by tubing  116 . Tubing  53  connects the stator port  44 - 2  of the first valve  40  to the stator port  112 - 5  of the second valve  110 . 
     Stator port  112 - 6  of the second valve  110  is connected stator port  66 - 3  of the sample manager valve  54  by tubing  22 ; stator port  112 - 4  of the second valve  110  is connected to stator port  66 - 2  of the sample manager valve  54  by tubing  24 ; and stator port  112 - 3  is connected to the column manager  26  by tubing  28 . 
     Like the embodiment of  FIG.  7   , in the embodiment of  FIG.  8   , the first valve  40  determines which of the two mixers  48 ,  100  is placed in the path of the gradient flowing from the BSM  12 , and the second valve  110  determines the flow direction, forward or reverse, through the sample manager  20 . Although the two mixers  48 ,  100  have the same reference numbers in  FIG.  7    and  FIG.  8   , in practice, the volumes of the mixers  48 ,  100  in  FIG.  7    can have the same or different volumes from corresponding mixers  48 ,  100  in  FIG.  8   . 
     In  FIG.  8   , the valve manager  14  is in a first configuration where the position of the first valve  40  places the mixer  48  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  110  establishes a forward direction flow through the sample manager  20 . 
     In a second configuration, the position of the first valve  40  places the other mixer  100  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  110  establishes a forward direction flow through the sample manager  20 . 
     In a third configuration, the position of the first valve  40  places the mixer  48  into the path of the gradient flow coming from the BSM  12 , while the position of the second valve  110  establishes a reverse direction flow through the sample manager  20 . 
     In a fourth configuration, the position of the first valve  40  places the other mixer  100  into the path of the gradient flow coming from the BSM  12 , and the position of the second valve  110  establishes a reverse direction flow through the sample manager  20 . 
     Each of these configurations can be initially qualified and, therefore, any change in selection among the four configurations does not require a subsequent requalification as a result of the change. 
       FIG.  9    shows a fifth embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . In this embodiment, the VM  14  has the same four-port first valve  90 , including the mixer  96 , as that described in  FIG.  6   , and the same six-port second valve  110 , as that described in  FIG.  8   . The stator port  92 - 4  of the first valve  90  is connected to the BSM  12 . Tubing  53  connects the stator port  92 - 3  of the first valve  90  to the stator port  112 - 5  of the second valve  110 . The tubing connections between the second valve  110  and the sample manager valve  54  are the same as those described in  FIG.  8   . 
     The first valve  90  determines whether the mixers  96  is placed in the path of the gradient flowing from the BSM  12 , and the second valve  110  determines the flow direction, forward or reverse, through the sample manager  20 . In the configuration shown, the position of the first valve  90  bypasses the mixer  96 , and that of the second valve  110  produces a forward direction flow through the sample manager  20 . Other configurations include a forward direction flow with the mixer  96  in the flow path, a reverse direction flow with the mixer  96  in the flow path, and a reverse direction flow with the mixer  96  bypassed. 
       FIG.  10    shows a sixth embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . This embodiment the valve manager  14  is the same as that described in  FIG.  8   , except the second valve  110  is configured with two mixers  118 ,  120  of different volumes, and the different tubing connections between the VM  14  and the sample manager  20 . The mixer  118  is connected between stator ports  112 - 1  and  112 - 6  of the second valve  110 ; and the mixer  120  is connected between stator ports  112 - 3  and  112 - 4  of the second valve  110 . Tubing  22  connects the stator port  44 - 2  of the first valve  40  with the stator port  66 - 3  of the sample manager valve  54 ; tubing  24  connects stator port  112 - 5  of the second valve  110  to the stator port  66 - 2  of the sample manager valve  54 ; and tubing  28  connects stator port  112 - 2  to the column manager  26 . 
     The embodiment of valve manager  14  in  FIG.  10    can produce forward direction gradient flow only through the sample manager  20 . The first valve  40  determines which of the two mixers  48 ,  100  is placed in the path of the gradient flowing from the BSM  12 , and the second valve  110  determines which of the two mixers  118 ,  120  is placed in the path of the sample composition flow arriving from the sample manager  20 . The two mixers  48 ,  100  determine changes to the system volume, whereas the two mixers  118 ,  120  determine changes to the sample dispersion volume. There are four different combination of mixers used to add volume to the LC system  10 : 1) mixers  48  and  118  as shown; 2) mixers  48  and  120 ; 3) mixers  100  and  118 ; and 4) mixers  100  and  120 . Each of these configurations can be initially qualified and, therefore, any change in selection among the four configurations does not require a subsequent qualification. 
       FIG.  11    shows a seventh embodiment of the valve manager  14  in communication with the sample manager  20  of  FIG.  2   . This embodiment the valve manager  14  is the same as that described in  FIG.  7   , except the second valve  42  is configured with one mixer  122 , and the tubing connections between the VM  14  and the sample manager  20 . The mixer  122  is connected between stator ports  50 - 1  and  50 - 2  of the second valve  42 . Tubing  22  connects the stator port  44 - 2  of the first valve  40  with the stator port  66 - 3  of the sample manager valve  54 ; tubing  24  connects stator port  50 - 4  of the second valve  42  to the stator port  66 - 2  of the sample manager valve  54 ; and tubing  28  connects stator port  50 - 3  to the column manager  26 . 
     The embodiment of valve manager  14  in  FIG.  11    can produce forward direction gradient flow only through the sample manager  20 . The first valve  40  determines which of the two mixers  48 ,  100  is placed in the path of the gradient flowing from the BSM  12 , and the second valve  42  determines whether the mixer  122  is placed in the path of the sample composition flow arriving from the sample manager  20 . The two mixers  48 ,  100  determine changes to the system volume, whereas the mixer  122  can be used to change to the sample dispersion volume. There are four different combination of mixers used to add volume to the LC system  10 : 1) mixer  48  only, as shown; 2) mixers  48  and  122 ; 3) mixers  100  and  122 ; and 4) mixer  100  only. Each of these configurations can be initially qualified and, therefore, any change in selection among the four configurations does not require a subsequent requalification as a result of the change. 
       FIG.  12    shows an embodiment of a valve pod  125  with a single valve  130  used to change the system volume of a chromatography system. The pod  125  containing the valve  130  may replace a conventional vent valve pod that is part of the BSM  12 . Except for changes to the plumbing, the valve  130  can be responsive to a valve drive previously used to operate the vent valve. The valve pod  125  gives the BSM  12  additional functionality (as described in  FIG.  12    and  FIG.  13   ), while maintaining conventional functionality (as described in connection with  FIG.  14    and  FIG.  15   ). Each position of the valve  130  (in combination with each position of a second valve, if any) can be initially qualified and, therefore, any change in selection of the valve position does not require a subsequent requalification as a result of the change. 
     The valve  130  has seven stator ports  132 - 1 ,  132 - 2 ,  132 - 3 ,  132 - 4 ,  132 - 5 ,  132 - 6 , and  132 - 7  (generally,  132 ) and three rotor channels  134 - 1 ,  134 - 2 ,  134 - 3  (generally,  134 ). Six of the stator ports  132 - 1 ,  132 - 2 ,  132 - 3 ,  132 - 4 ,  132 - 5 , and  132 - 6  are symmetrically disposed along a radius of an imaginary circle on the stator; the seventh stator port  132 - 7  is at the center of the stator. Rotor channels  134 - 1  and  134 - 2  are arcuate in shape, and rotor channel  134 - 3  is linear. Each of the arcuate rotor channels  134 - 1 ,  134 - 2  connects together two stator ports  132  on the radius of the imaginary circle. Rotor channel  134 - 3  connects the center stator port  132 - 7  to one of the stator ports on the radius. In addition, a mixer  136  is connected between stator ports  132 - 1  and  132 - 4 . The stator port  132 - 5  is connected to the BSM  12  through a second mixer  138 . This second mixer  138  is external to the valve pod  125  and may be part of the BSM  12 . Stator port  132 - 2  is connected to the sample manager  20  through tubing  140 . 
     In the configuration shown in  FIG.  12   , only the second mixer  138  is in the flow path. Arcuate rotor channel  134 - 1  connects stator ports  132 - 5  and  132 - 6 , arcuate rotor channel  134 - 2  connects stator ports  132 - 2  and  132 - 3 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 1 . 
     During operation of the LC system  10 , the BSM  12  pumps gradient through the mixer  138  into the stator port  132 - 5  of the valve  130  of the valve pod  125 . From the stator port  132 - 5 , the gradient passes through the rotor channel  134 - 1  to the stator port  132 - 6 . Passing through tubing  137 , the gradient arrives at the stator port  132 - 3 . The gradient then passes through the rotor channel  134 - 2  to exit the valve  130  through stator port  132 - 2 . From the stator port  132 - 2 , the gradient exits the valve pod  125  for delivery through tubing  140  to a stator port of the valve  54  ( FIG.  2   ) of the sample manager  20  or to a second valve of a valve manager. In this configuration, the volume of the mixer  136  is not in the flow path and, thus, not included in the system volume. 
       FIG.  13    shows the embodiment of the valve pod  125  of  FIG.  12    with the single valve  130  in a position that places the mixer  136  into the flow path in series with the second mixer  138 . With respect to  FIG.  12   , the rotor is turned two steps clockwise (or four steps counterclockwise). In the position shown, arcuate rotor channel  134 - 1  connects stator ports  132 - 1  and  132 - 2 , arcuate rotor channel  134 - 2  connects stator ports  132 - 4  and  132 - 5 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 3 . 
     During operation, the BSM  12  pumps gradient through the mixer  138  into the stator port  132 - 5  of the valve  130  of the valve pod  125 . From the stator port  132 - 5 , the gradient passes through the rotor channel  134 - 2  to the stator port  132 - 4 . The gradient then passes through the mixer  136  to the stator port  132 - 1 , then through rotor channel  134 - 1  to exit the valve  130  through stator port  132 - 2 . From the stator port  132 - 2 , the gradient exits the valve pod  125  for delivery through tubing  140  to a stator port of the valve  54  ( FIG.  2   ) of the sample manager  20  or to a second valve of a valve manager. In this configuration, the volume of both mixers  136 ,  138  are in the flow path. 
       FIG.  14    shows the embodiment of the valve pod  125  of  FIG.  12    with the single valve  130  in a dead-end position to facilitate a leak test. With respect to  FIG.  12   , the rotor is turned one step clockwise (or five steps counterclockwise). In the position shown, arcuate rotor channel  134 - 1  connects stator ports  132 - 1  and  132 - 6 , arcuate rotor channel  134 - 2  connects stator ports  132 - 3  and  132 - 4 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 2 . In this position, the valve  130  has no flow path from the BSM  12  to the sample manager  20 , and the mixer  136  is part of an isolated loop formed together with the rotor channels  134 - 1  and  134 - 2  and the connection  137  between the channels. 
       FIG.  15    shows the embodiment of the valve pod  125  of  FIG.  12    with the single valve  130  in a position to vent the flow path. With respect to  FIG.  12   , the rotor is turned four steps clockwise (or two steps counterclockwise). In the position shown, arcuate rotor channel  134 - 1  connects stator ports  132 - 3  and  132 - 4 , arcuate rotor channel  134 - 2  connects stator ports  132 - 1  and  132 - 6 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 5 . In this position, the flow path from the BSM  12  passes through a vent tube  142  into waste. As in  FIG.  14   , the mixer  136  is part of an isolated loop formed together with the rotor channels  134 - 1  and  134 - 2  and the connection  137  between the channels. 
       FIG.  16    through  FIG.  19    show the embodiment of the valve pod  125  of  FIG.  12   , having the single valve  130 , configured with both mixers  136 ,  138  (i.e., the mixer  138  that was external to the valve pod  125  in  FIG.  12    is here integrated into the valve pod  125 ). As described in  FIG.  12   , the valve pod  125  may replace a conventional vent valve pod that is part of the BSM  12 , to give the BSM  12  additional functionality (as described in  FIG.  16    and  FIG.  17   ), while maintaining conventional functionality (as described in connection with  FIG.  18    and  FIG.  19   ). Each position of the valve  130  (in combination with each position of a second valve, if any) can be initially qualified and, therefore, any change in selection of the valve position does not require a subsequent requalification as a result of the change. 
     In each of the  FIG.  16    through  FIG.  19   , the second mixer  138  is connected between the stator port  132 - 6  and the stator port  132 - 3  of the valve  130 . The connection of the first mixer  136  between stator ports  132 - 1 ,  132 - 4  and the other connections between the rotor channels  134  and stator ports  132  in  FIG.  16    through  FIG.  19    are the same as those described in connection with  FIG.  12    through  FIG.  15   , respectively. 
     In  FIG.  16   , the position of the single valve  130  has only the second mixer  138  in the flow path from the BSM  12  to the sample manager  20 . The flow path passes from the BSM  12  to the stator port  132 - 5  of the valve  130 , from the stator port  132 - 5  through the rotor channel  134 - 1  to the stator port  132 - 6 , from the stator port  132 - 6  through the second mixer  138  to the stator port  132 - 3 . From the stator port  132 - 3 , the flow path continues through the rotor channel  134 - 2  to stator port  132 - 2  and exits the valve pod  125  through tubing  140  to a stator port of the valve  54  ( FIG.  2   ) of the sample manager  20  or a second valve of a valve manager. In this configuration, the volume of the first mixer  136  is not in the flow path and, thus, not included in the system volume, such as illustrated in  FIG.  12   . 
       FIG.  17    shows the position of the single valve  130  wherein only the first mixer  136  is in the flow path from the BSM  12  to the sample manager  20 . With respect to  FIG.  16   , the rotor is turned two steps clockwise (or four steps counterclockwise). In this position shown, the connections are the same as those described in connection with  FIG.  13   : arcuate rotor channel  134 - 1  connects stator ports  132 - 1  and  132 - 2 ; arcuate rotor channel  134 - 2  connects stator ports  132 - 4  and  132 - 5 ; and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 3 . 
     The flow path passes from the BSM  12  to the stator port  132 - 5 , from the stator port  132 - 5  through the rotor channel  134 - 2  to the stator port  132 - 4 , from the stator port  132 - 4  through the first mixer  136  to the stator port  132 - 1 . From the stator port  132 - 1 , the flow path continues through the rotor channel  134 - 1  to stator port  132 - 2  and exits the valve pod  125  through tubing  140  to a stator port of the valve  54  ( FIG.  2   ) of the sample manager  20 . In this configuration, the volume of the second mixer  138  is not in the flow path and, thus, not included in the system volume. 
       FIG.  18    shows the valve  130  in a dead-end position to facilitate a leak test. With respect to  FIG.  16   , the rotor is turned one step clockwise (or five steps counterclockwise). In the position shown, arcuate rotor channel  134 - 1  connects stator ports  132 - 1  and  132 - 6 , arcuate rotor channel  134 - 2  connects stator ports  132 - 3  and  132 - 4 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 2 , just as described in connection with  FIG.  14   . In this position, the valve  130  has no flow path from the BSM  12  to the sample manager  20 , and both mixers  136 ,  138  are part of an isolated loop formed together with the rotor channels  134 - 1  and  134 - 2 . 
       FIG.  19    shows the valve  130  in a position to vent the flow path. With respect to  FIG.  16   , the rotor is turned four steps clockwise (or two steps counterclockwise). In the position shown, arcuate rotor channel  134 - 1  connects stator ports  132 - 3  and  132 - 4 , arcuate rotor channel  134 - 2  connects stator ports  132 - 1  and  132 - 6 , and linear rotor channel  134 - 3  connects center stator port  132 - 7  to stator port  132 - 5 , just as described in connection with  FIG.  15   . In this position, the flow path from the BSM  12  passes through a vent tube  142  into waste. As in  FIG.  18   , the mixers  136 ,  138  are part of an isolated loop formed together with the rotor channels  134 - 1  and  134 - 2 . 
       FIG.  20    shows an embodiment of a process  150  that uses a reconfigurable valve manager  14  to facilitate changing system volume, sample dispersion volume, or both of an LC system without requiring requalification as a result of the change. At step  152 , the valve manager is put into a first configuration, for example, one without any mixer in the flow path as in  FIG.  2   . While in this configuration, the system is qualified (step  154 ). If there are other configurations to be qualified, the VM  14  is placed (step  156 ) into the next select configuration, and then the LC system is qualified (step  154 ) with the VM in that configuration. The qualification of the LC system  10  with each subsequently selected VM configuration continues until all desired configurations are qualified. The information gathered during the qualifications can be stored to establish a performance baseline for each of the configurations. 
     After all desired VM configurations are qualified, the LC system can perform (step  158 ) a chromatography run in one of the selected configuration. Then, when, at step  160 , another of the qualified VM configurations is selected, the LC system  10  can perform (step  162 ) a chromatography run in using that selected configuration without having to qualify the LC system before doing so. 
     As will be appreciated by one skilled in the art, aspects of the present invention may be embodied as a system, method, or computer program product. Accordingly, aspects of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system.” Furthermore, aspects of the present invention may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon. 
     Any combination of one or more computer readable storage medium(s) may be utilized. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device. 
     Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wire-line, optical fiber cable, RF, etc., or any suitable combination of the foregoing. Computer program code for carrying out operations for aspects of the present invention may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the “C” programming language or similar programming languages. 
     Aspects of the present invention are described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks. 
     These computer program instructions may also be stored in a computer readable storage medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function/act specified in the flowchart and/or block diagram block or blocks. 
     The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks. 
     The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. 
     It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions. 
     It is to be understood that such terms like above, below, upper, lower, left, leftmost, right, rightmost, top, bottom, front, and rear are relative terms used for purposes of simplifying the description of features as shown in the figures, and are not used to impose any limitation on the structure or use of any thermal systems described herein. While the invention has been shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the following claims.