Patent Publication Number: US-2015083947-A1

Title: Back pressure regulation

Description:
RELATED APPLICATION 
     This application claims priority to and benefit of U.S. Provisional Patent Application No. 61/608,219 entitled “Back Pressure Regulation,” filed Mar. 8, 2012, which is incorporated by reference herein in its entirety. 
    
    
     TECHNICAL FIELD 
     This disclosure relates to back pressure regulation, and, in one particular implementation, to a dynamic back pressure regulator for a supercritical fluid chromatography system. 
     BACKGROUND 
     Supercritical fluid chromatography (SFC) is a chromatographic separation technique that typically utilizes liquefied carbon dioxide (CO 2 ) as a mobile phase solvent. In order to keep the mobile phase in liquid (or liquid-like density) form, the chromatographic flow path is pressurized; typically to a pressure of at least 1100 psi. 
     SUMMARY 
     This disclosure is based, in part, on the realization that a dynamic back pressure regulator can be provided with a needle having a polymer (e.g., polyether-ether-ketone or polyimide) tip for improved resistance to corrosion and/or erosion. 
     On aspect provides a dynamic back pressure regulator that includes an inlet, an outlet, a seat disposed between the inlet and the outlet and defining at least part of a fluid pathway, and a needle displaceable relative to the seat to form a restriction region therebetween for restricting fluid flow between the inlet and the outlet. The needle includes a corrosion and erosion resistant polymer tip. 
     Another aspect features a supercritical fluid chromatography (SFC) system that includes a separation column, at least one pump configured to deliver a mobile phase fluid flow comprising liquefied CO2 toward the separation column, an inject valve configured to introduce a sample plug into the mobile phase fluid flow, and a dynamic back pressure regulator disposed downstream of, and in fluid communication with, the column for regulating pressure in the system. The dynamic back pressure regulator includes an inlet, an outlet, a seat disposed between the inlet and the outlet and defining at least part of a fluid pathway, and a needle displaceable relative to the seat to restrict fluid flow between the inlet and the outlet. The needle includes a corrosion and erosion resistant polymer tip. 
     According to another aspect, a method includes delivering a mobile phase fluid flow comprising liquefied carbon dioxide (CO2) from a chromatography toward a dynamic back pressure regulator; and passing the mobile phase fluid flow through a restriction region in the dynamic back pressure regulator defined by a seat, and a needle that includes a corrosion and erosion resistant polymer tip. 
     Implementation can include one or more of the following features. 
     In some implementations, the corrosion and erosion resistant polymer is selected from polyether-ether-ketone and polyimide. 
     In certain implementations, the needle includes a stem connected to the tip. The stem is made of a metal. 
     In some implementations, the metal for the stem is selected from stainless steel, MP35N, and titanium. 
     In certain implementations, the tip is threadingly connected to the stem. 
     In some implementations, the tip is overmolded on the stem. 
     In certain implementations, the stem includes barbs for mounting the tip. 
     In some implementations, the seat is at least partially formed of a polymer (e.g., polyether-ether-ketone). 
     In certain implementations, the polymer at least partially forming the seat is filled with between 20 and 50 wt. % carbon fiber (e.g., about 30 wt. % carbon fiber). 
     In some implementations, the seat is at least partially formed of a chemically resistant ceramic (e.g., sapphire and zirconia). 
     In certain implementations, the tip includes a tapered portion in the shape of a cone. 
     In some implementations, the cone has an included angle of about 30 degrees to about 60 degrees. 
     In certain implementations, the total displacement of the needle relative to seat is about 0.001 inches to about 0.005 inches. 
     In some implementations, the dynamic back pressure regulator can also include a solenoid configured to limit displacement of the needle relative to the seat to control the restriction of fluid flow. 
     In certain implementations, the dynamic back pressure regulator can also include a head defining a portion of the fluid pathway, and a body connecting the solenoid to the head, 
     In some implementations, the needle includes a proximal end that extends into the body, and a distal end that extends into the head. 
     In certain implementations, the dynamic back pressure regulator also includes a seat nut that engages the head to secure the seat therebetween. 
     In some implementations, the head defines the inlet port and the seat nut defines the outlet port. 
     In certain implementations, the dynamic back pressure regulator also includes a seal disposed between the head and the body. The needle extends through the seal. 
     In some implementations, the dynamic back pressure regulator can also include a bushing disposed between the head and the body, wherein the needle extends through the bushing. 
     In certain implementations, the dynamic back pressure regulator is configured to regulate fluid pressure at the inlet port to a pressure within the range of about 1500 psi to about 6000 psi. 
     In some implementations, a flow of electrical current to dynamic back pressure regulator is changed to adjust the size of the restriction region. 
     In certain implementations, the step of delivering the mobile phase fluid flow from the chromatography column toward the dynamic back pressure regulator includes: delivering the mobile phase fluid flow from the chromatography column toward a detector, and then delivering the mobile phase fluid flow from the detector toward the dynamic back pressure regulator. 
     Implementations can provide one or more of the following advantages. 
     Implementations provide a needle that is resistant to corrosion, erosion, or any combination thereof in the back pressure regulator environment of a supercritical fluid chromatography system. 
     Other aspects, features, and advantages are in the description, drawings, and claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of a supercritical fluid chromatography (SFC) system; 
         FIG. 2  is a schematic view of a dynamic back pressure regulator from the SFC system of  FIG. 1 ; 
         FIG. 3A  is an exploded view of a needle from the dynamic back pressure regulator of 
         FIG. 2 ; 
         FIG. 3B  is a cross-section view of a tip of the needle from  FIG. 3A ; 
         FIG. 3C  is a perspective view of the needle from the dynamic back pressure regulator of  FIG. 2 ; 
         FIG. 4  is cross-section view of an implementation of the needle with the tip mounted on the stem via barbs; and 
         FIG. 5  is a cross-section view of an implementation of the needle with the tip mounted on the stem via overmolding. 
     
    
    
     Like reference numbers indicate like elements. 
     DETAILED DESCRIPTION 
     System Overview 
       FIG. 1  schematically depicts a supercritical fluid chromatography (SFC) system  100 . The SFC system  100  includes a plurality of stackable modules including a solvent manager  110 ; an SFC manager  140 ; a sample manager  170 ; a column manager  180 ; and a detector module  190 . 
     The solvent manager  110  is comprised of a first pump  112  which receives carbon dioxide (CO2) from CO2 source  102  (e.g., a tank containing compressed CO2). The CO2 passes through an inlet shutoff valve  142  and a filter  144  in the SFC manager  140  on its way to the first pump  112 . The first pump  112  can comprise one or more actuators each comprising or connected to cooling means, such as a cooling coil and/or a thermoelectric cooler, for cooling the flow of CO2 as it passes through the first pump  112  to help ensure that the CO2 fluid flow is deliverable in liquid form. In some cases, the first pump  112  comprises a primary actuator  114  and an accumulator actuator  116 . The primary and accumulator actuators  114 ,  116  each include an associated pump head, and are connected in series. The accumulator actuator  116  delivers CO2 to the system  100 . The primary actuator  114  delivers CO2 to the system  100  while refilling the accumulator actuator  116 . 
     In some cases, the solvent manager  110  also includes a second pump  118  for receiving an organic co-solvent (e.g., methanol, water (H2O), etc.) from a co-solvent source  104  and delivering it to the system  110 . The second pump  118  can comprise a primary actuator  120  and an accumulator actuator  122 , each including an associated pump head. The primary and accumulator actuators  120 ,  122  of the second pump  118  are connected in series. The accumulator actuator  122  delivers co-solvent to the system  100 . The primary actuator  120  delivers co-solvent to the system  100  while refilling the accumulator actuator  122 . 
     Transducers  124   a - d  are connected to outlets of the respective pump heads for monitoring pressure. The solvent manager  110  also includes electrical drives for driving the primary actuators  114 ,  120  and the accumulator actuators  116 ,  122 . The CO2 and co-solvent fluid flows from the first and second pumps  112 ,  118 , respectively, and are mixed at a tee  126  forming a mobile phase fluid flow that continues to an injection valve subsystem  150 , which injects a sample slug for separation into the mobile phase fluid flow. 
     In the illustrated example, the injection valve subsystem  150  is comprised of an auxiliary valve  152  that is disposed in the SFC manager  140  and an inject valve  154  that is disposed in the sample manager  170 . The auxiliary valve  152  and the inject valve  152  are fluidically connected and the operations of these two valves are coordinated to introduce a sample plug into the mobile phase fluid flow. The inject valve  154  is operable to draw up a sample plug from a sample source (e.g., a vial) in the sample manager  170  and the auxiliary valve  152  is operable to control the flow of mobile phase fluid into and out of the inject valve  154 . The SFC manager  140  also includes a valve actuator for actuating the auxiliary valve  152  and electrical drives for driving the valve actuations. Similarly, the sample manager  170  includes a valve actuator for actuating the inject valve and  154  and electrical drives for driving the valve actuations. 
     From the injection valve subsystem  150 , the mobile phase flow containing the injected sample plug continues through a separation column  182  in the column manager  180 , where the sample plug is separated into its individual component parts. The column manager  180  comprises a plurality of such separation columns, and inlet and outlet switching valves  184 ,  186  for switching between the various separation columns. 
     After passing through the separation column  182 , the mobile phase fluid flow continues on to a detector  192  (e.g., a flow cell/photodiode array type detector) housed within the detector module  190  then through a vent valve  146  and then on to a back pressure regulator assembly  200  in the SFC manager  140  before being exhausted to waste  106 . A transducer  149  is provided between the vent valve  146  and the back pressure regulator assembly  200 . 
     The back pressure regulator assembly  200  includes a dynamic (active) back pressure regulator  202  and a static (passive) back pressure regulator  204  arranged in series. The dynamic back pressure regulator  202 , which is discussed in greater detail below, is adjustable to control or modify the system fluid pressure. This allows the pressure to be changed from run to run. The properties of CO 2  affect how quickly compounds are extracted from the column  182 , so the ability to change the pressure can allow for different separation based on pressure. 
     The static back pressure regulator  204  is a passive component (e.g., a check valve) that is set to above the critical pressure, to help ensure that the CO2 is liquid through the dynamic back pressure regulator  202 . The dynamic back pressure regulator  202  can control more consistently when it is liquid on both the inlet and the outlet. If the outlet is gas, small reductions in the restriction can cause the CO 2  to gasify upstream of the dynamic back pressure regulator  202  causing it to be unable to control. In addition, this arrangement helps to ensure that the static back pressure regulator  204  is the location of phase change. The phase change is endothermic, therefore the phase change location may need to be heated to prevent freezing. By controlling the location of phase change, the heating can be simplified and localized to the static back pressure regulator  204 . 
     Generally, the static back pressure regulator  204  is designed to keep the pressure at the outlet of the dynamic back pressure regulator  202  below 1500 psi but above the minimum pressure necessary to keep the CO2 in liquid phase. In some cases, the static back pressure regulator  204  is designed to regulate the pressure within the range of about 1150 psi (at minimum flow rate) to about 1400 psi (at maximum flow rate). The dynamic back pressure regulator  202  can be used to regulate system pressure in the range of about 1500 psi to about 6000 psi. 
     Also shown schematically in  FIG. 1  is a computerized system controller  108  that can assist in coordinating operation of the SFC system  100 . Each of the individual modules  110 ,  140 ,  170 ,  180 ,  190  also includes its own control electronics, which can interface with each other and with the system controller  108  via an Ethernet connection  109 . The control electronics for each module can include non-volatile memory with computer-readable instructions (firmware) for controlling operation of the respective module&#39;s components (e.g., the pumps, valves, etc.) in response to signals received from the system controller  108  or from the other modules. Each module&#39;s control electronics can also include at least one processor for executing the computer-readable instructions, receiving input, and sending output. The control electronics can also include one or more digital-to-analog (D/A) converters for converting digital output from one of the processors to an analog signal for actuating an associated one of the pumps or valves (e.g., via an associated pump or valve actuator). The control electronics can also include one or more analog-to-digital (A/D) converters for converting an analog signal, such as from system sensors (e.g., pressure transducers), to a digital signal for input to one of the processors. In some cases, some or all of the various features of these control electronics can be integrated in a microcontroller. 
     Dynamic Back Pressure Regulator 
     Referring to  FIG. 2 , an implementation of a dynamic back pressure regulator  202  for use in chromatographic separations includes a body  208 , a head  210  fastened to the body  208 , a seat  212 , and a seat nut  214  which is threadingly received within a counterbore  211  in the head  210  securing the seat  212  therebetween. The head  210 , the seat  212 , and the seat nut  214  together define a fluid pathway  215  that connects an inlet port  216  in the head  210  to an outlet port  218  in the seat nut  214 . That is, the fluid pathway  215  is formed by the interconnection of cavities and passageways in the head  210 , the seat  212 , and the seat nut  214 . The inlet and outlet ports  216 ,  218  are each configured to receive a standard compression screw and ferrule connection for connecting fluidic tubing. 
     The dynamic back pressure regulator  202  also has a needle  220  which extends into the fluid pathway  215 . The needle  220  is displaceable relative to the seat  212  to adjust a restriction region defined between the needle  220  and the seat  212  for controlling fluid flow through the fluid pathway  215 . During operation, the total displacement of the needle  220  is between about 0.001 inches and 0.005 inches. For example, at about 2000 psi the displacement of the needle  220  is barley 0.001 inches, leaving about a 0.001 inch gap between the needle  220  and seat  212  where fluid can flow. Consequently, the fluid velocity within the dynamic back pressure regulator  202  tends to be high. In general, during normal operation, the needle  220  is not intended to completely seal against the seat  212  in a manner that completely stops flow, but instead is intended to merely restrict the flow to achieve the desired pressure. The seat  212  can be manufactured from polyether-ether-ketone, such as PEEK™ polymer (available from Victrex PLC, Lancashire, United Kingdom), filled with between 20 and 50 wt. % (e.g., 30 wt. %) carbon fiber. Alternatively, the seat  212  can be manufactured from a chemically resistant ceramic such as sapphire or zirconia. 
     The needle  220  is supported in a through hole  221  in the head  210  and is arranged such that a distal end  222  of the needle  220  is in the fluid pathway  215 . The needle  220  passes through a seal  230  which inhibits flowing fluids from passing into the body  208  and extends through a bushing  232 . The bushing  232  is secured between the head  210  and a body  208  which is connected to the head  210  (e.g., by means of fasteners such as screws). A proximal end  224  of the needle  220  extends outwardly from the bushing  232  and into a first cavity  234  in the body  208 . 
     The needle  220  can be actuated by a solenoid  240  which is connected to the body  208  (e.g., by means of fasteners such as screws). The solenoid  240  comprises a housing  242  and a plunger  244  that includes an outer shaft  246  and an inner shaft  248 . An electrical coil  250  for activating the solenoid  240  is disposed within the housing  242 . A distal end portion  245  of the plunger  244  extends through a second cavity  252  in the body  208  and into the fist cavity  234  via a reduced diameter through hole  254 . When the solenoid  240  is activated, a distal end  249  of the inner shaft  248  pushes against the proximal end  224  of the needle  220 , which displaces the needle  220  towards the seat  212  to restrict fluid flow. Pressure force (fluid) will move the needle  220  until the fluidic pressure force on the needle  220  matches the force applied by the solenoid  240 . In this regard, the fluid pressure creates whatever restriction is necessary to equalize the pressure force from the solenoid. 
     A balancing spring collar  260  is fastened about a distal end  247  of the plunger&#39;s outer shaft  246  and retains a balancing spring  262  between the housing  242  and the balancing spring collar  260 . The balancing spring  262  is provided to balance the solenoid  240  to have minimal force change through the working stroke of the plunger  244 . As the plunger  244  moves out of the magnetic field the force drops off. The balancing spring  262  is selected to make the spring rate positive so that the plunger  244  has a returning force. The chosen spring adds an equivalent to slightly higher positive (stabilizing) spring rate. 
     A calibration collar  270  is fastened about a proximal end portion  271  of the plunger  244 . The calibration collar  270  includes a first clamping section  272  that secures the calibration collar  270  to the proximal end  273  of the outer shaft  246 , and a second clamping section  274  that secures the calibration collar  270  to the inner shaft  248 . The calibration collar  270  secures a calibration spring  276  between the proximal end  275  of the inner shaft  248  and the calibration collar  270 . The calibration spring  276  proves for a mechanical self calibration of the plunger  244  during assembly. That is, during assembly of the dynamic back pressure regulator  202  the first clamping section  272  is fastened to the proximal end  273  of the outer shaft  246  while the second clamping section  274  is left loose to allow the inner shaft  248  to move relative the outer shaft  246 . This allows the calibration spring  276  to move the inner shaft  248  into contact with the needle  220 . Consequently, the needle  220  is moved into contact with the seat  212 , thereby calibrating the needle position. The engagement of the needle  220  with the seat  212  also helps to center the needle  220  and the seat  212 . The second clamping section  274  can then be fastened to the inner shaft  248  to inhibit movement of the inner shaft  248  relative to the outer shaft  246  during normal operation. 
     Needle 
     During operation, the dynamic back pressure regulator  202  in the SFC system  100  can provide an exceptionally corrosive and erosive environment for the needle  220  and the seat  212 . The combination of CO 2  and water or organic solvent can be very corrosive. In addition, the high velocity flow through the restriction region defined between the needle  220  and seat  212  can expose the needle  220  and seat  212  to significant erosive forces. When the two conditions are combined the needle  220  and the seat  212  are exposed to a highly destructive environment, which can lead to degradation of the needle  220 , and, consequently, loss of control over the pressure. The pressure drop across the dynamic back pressure regulator  202 , from between about 1500 psi to about 6000 psi at the inlet of the dynamic back pressure regulator to between about 1150 psi to about 1400 psi at the outlet of the dynamic back pressure regulator  202  may also result in localized phase change of the CO2 along the needle  220  which can also contribute to erosion. 
     In the following, the needle  220  is described in more detail with reference to  FIGS. 3A &amp; 3B . Notably, the needle  220  can be provided with a corrosion and erosion resistant polymer (e.g., polyether-ether-ketone or polyimide) tip, which is the portion of the needle  220  that forms the restriction region with the seat  212 . The utilization of such material can allow the needle  220  to survive the harsh environment that it is exposed to. 
     Referring to  FIG. 3A , the needle  220  includes a stem  280  and a tip  282  that is connected the stem  280  and which forms the restriction region with the seat  212 . The stem  280  includes a flange  284 , a threaded projection  286 , and an elongate shaft  288  that extends between the flange  284  and the threaded projection  286 . Following assembly, the flange  284  is disposed within the first cavity  234  in the body  208  and can serve as a hard stop against the bushing  232  ( FIG. 2 ) and a shoulder formed at the junction of the first cavity  234  ( FIG. 2 ) and the reduced diameter through hole  254  ( FIG. 2 ). The stem  280  can be formed from a metal such as stainless steel, MP35N, titanium, etc. 
     The tip  282  includes a threaded counter bore  290  which mates with the threaded projection  286  to secure the tip  282  to the stem  280 . In some cases, the threaded counter bore  290  is provided with an incomplete thread, leaving an unthreaded section  291  ( FIG. 3B ), which is deformed when the tip  282  is threaded on the stem  280  to provide a deformation fit. The tip  282  may also include another counter bore  292  ( FIG. 3B ) which has a close fit (e.g., a 0 to 0.002 inch gap) with a shoulder  293  on the stem  280  for alignment to ensure that the tip  282  is straight. The tip  282  also includes a tapered portion in the shape of a cone  294 . The cone  282  has an included angle of about  30  degrees to about  60  degrees. The cone  294  cooperates with the seat  212  to restrict fluid flow. The cone  294  also helps to center the seat  212  during assembly. That is, during assembly, as the seat nut  214  is tightened into the head  210  the cone  282  engages a cavity in the proximal end of the seat  212  which assists in centering the seat  212 . The tip  282  is formed of a corrosion and erosion resistant polymer (e.g., polyether-ether-ketone, such as PEEK™ polymer (available from Victrex PLC, Lancashire, United Kingdom), or polyimide (available as DuPont™ VESPEL® polyimide from E. I. du Pont de Nemours and Company)). 
     Referring to  FIG. 3C , the needle  220  has an overall length L of about 0.75 inches to about 1.5 inches. The stem  280  and tip  282  have a diameter d of about 0.124 inches to about 0.126 inches (e.g., about 0.125 inches), which leaves a clearance of about 0.005 inches between the shaft  280  and the through hole  221  ( FIG. 2 ) in the head  210  following assembly. 
     This combination of needle materials provides the structural advantages of a metal stem with a tip that will resist corrosion and erosion when exposed to corrosive chemicals (e.g., carbonic acid) and high fluid velocities. It was found that this needle combined with a carbon fiber filled polyether-ether-ketone seat is extremely well suited to this environment and has shown little to no wear over time. A dynamic back pressure regulator  202  with this arrangement of needle and seat materials remained fully functional following testing at 100 liters of flow at a flow rate of 4 mL/min through the restriction region. 
     Other Implementations 
     Although a few implementations have been described in detail above, other modifications are possible. For example, while an implementation of a needle has been described in which a corrosion and erosion resistant polymer tip is threadingly attached to a rigid metal stem, in some cases, the stem  280  may instead be provided with one or more barbs  290  for engaging a counter bore  292  in the tip  282 , as shown in  FIG. 4 . 
     Alternatively, the tip may be overmolded on the stem. For example,  FIG. 5  illustrates an implementation in which the tip  282  is overmolded on the stem  280 . The stem  280  is provided with an overmold feature  300  to help ensure that the overmolded tip  282  does not slip off the stem  280 . 
     While an implementation of a dynamic back pressure regulator has been described which uses a solenoid for regulating the displacement of the needle relative to the seat, some implementations may utilize another type of actuator, e.g., a linear position component, such as a voice coil, for regulating the displacement of the needle. 
     In addition, although described with respect to SFC applications, the principles can be implemented in back pressure regulators used in other applications which involve the handling of corrosive fluids and/or high velocity fluid flows. In some instances, for example, the back pressure regulators described herein may be desirable for regulating system pressure in other types of chromatography systems, such as high performance liquid chromatography (HPLC) systems. 
     While implementations have been describe in which the needle tip is formed of a corrosion and erosion resistant polymer, in some cases, the tip may instead include a corrosion and erosion resistant metal plating (e.g., a gold plating or a platinum plating). For example, the tip may be formed of a metal (such as stainless steel, aluminum, titanium) that is provided with a metal plating. Alternatively, the needle tip may be formed (e.g. machined from) a corrosion and erosion resistant metal such as gold or platinum. 
     Accordingly, other implementations are within the scope of the following claims.