Abstract:
An adjustable high pressure, low flow metering valve provides a sleeve extending about a restrictor shaft, the sleeve having a narrow helical groove formed in the inside diameter. A restrictor shaft within the sleeve encloses the groove and forms a sealed helical flow channel. The length of the flow channel is varied by withdrawing the restrictor shaft in the sleeve, whereby only a selected axial extent of the groove is enclosed by the sleeve to form a confined flow path. The shaft is provided with a threaded engagement in the body of the metering valve, so that rotation of an adjustment knob provides extremely fine control of the length of the flow path, and thus highly accurate selection of the flow resistance.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
   This application is a division of Ser. No. 10/390,142, filed Mar. 18, 2003, now abandoned. 

   FEDERALLY SPONSORED RESEARCH 
   Not applicable. 
   SEQUENCE LISTING, ETC ON CD 
   Not applicable. 
   BACKGROUND OF THE INVENTION 
   1. Field of the Invention 
   The present invention relates to fluid flow control, and, more particularly, to an improved method and apparatus to generate extremely low flow rates at high pressures that are accurately regulated for use in liquid chromatography and mass spectrometry. 
   2. Description of Related Art 
   In liquid chromatography, the liquid (solvent) flow rates generally used are between 100 μliters/min and 10 ml/min. However, more widespread use of capillary and micro-bore columns, as well as new applications such as combining liquid chromatography with mass spectrometry has created a requirement for flow rates that are as much as 100 times lower than the above mentioned flow rates. Very few HPLC pumps are capable of delivering accurate, stable flow rates in this range, and those that can do so are extremely expensive. As a result, most manufacturers have adopted a method known as flow splitting to achieve low flow rates with conventional high pressure liquid chromatography pumps. In the prior art, flow splitting is accomplished by using a tee to split the flow into two paths. Capillary tubes of different lengths and/or diameters are used on each path to create different fluid resistance in each path. Because these flow rates are all in the laminar flow regime, the resulting flow rates in each path can be found from the following relation: 
             Δ   ⁢           ⁢   P     =       μ   ⁢           ⁢   LQ       d   4             
where P is pressure, μ is dynamic viscosity, L is capillary flow length, Q is flow rate, and d is effective capillary diameter.
 
   The significant disadvantages of prior art include:
         Capillary tube is easy to clog.   Split ratios may change during a chromatographic run because of changes in fluid viscosity that occur during the run. This may occur because the volume in the capillary tubing can be large enough that the composition of solvents can become different in the two legs when the pre-split composition is changing.   Difficult to adjust split flow ratio. It is necessary to cut the tubing to different lengths to adjust the split ratio. This is difficult to do because the capillary usually closes off due to crimping in the cutting process available to most chromatographers in the lab, and thus the fluid resistance changes unpredictably. Also, it is necessary to cut and join additional pieces of tubing to add resistance. This is a troublesome and time consuming process because of the small tube and fitting size.   Verifying the flow rate is extremely difficult. There are no commercially available flow meters that work at these low flow rates. Measuring flow rates as low as 100 nanoliters per minute must be done by weighing the effluent on the low path side over a known time interval. This is very time intensive. Using traditional methods, such as pressure drop through a known capillary, do not work because the viscosity of the fluids is often changing over time, and is unknown.
 
When the capillary analytical column is added to the low flow path, the split ratio is changed. The resistance of analytical columns is usually unknown, and will change with a change in solvent viscosity. Thus, it is necessary for the user to measure flow rates after adding the column to the flow splitter.
       

   BRIEF SUMMARY OF THE INVENTION 
   The present invention generally comprises a method and apparatus for controlling and regulating the high pressure, low flow systems used in HPLC and the like. 
   A major aspect of the invention is the design of an adjustable high pressure, low flow metering valve. Other prior art devices have attempted to use orifice metering. This approach works well at high flow rates, but is unstable at these low flows and high pressures. Even a change in diameter of one millionth of an inch in the orifice diameter will produce an unacceptable change in back pressure. The present invention provides a sleeve that extends about a restrictor shaft, the sleeve having a narrow helical groove formed in the inside diameter thereof. A restrictor shaft is disposed within the sleeve in a press fit to enclose the groove and form a sealed helical flow channel that approximates a very small diameter capillary with a rather long path length. The long path tends to negate variations in effective diameter over the length of the flow path. The adjustment in fluid resistance is made by adjusting the length of the flow path. This is accomplished by changing the length of engagement of the restrictor shaft with the helical flow path created between the shaft and the bore. The length of the flow channel is varied by withdrawing the restrictor shaft in the sleeve, whereby only a selected axial extent of the groove is enclosed by the sleeve to form a confined flow path. The shaft is provided with a threaded engagement in the body of the metering valve, so that rotation of an adjustment knob provides extremely fine control of the length of the flow path, and thus highly accurate selection of the flow resistance. 
   The flow path is a groove having a 60° triangular cross-section which is provided to resist clogging. This groove has a flow resistance approximately the same as a tubular path having a diameter that fits within the 60° triangle, yet the triangular configuration permits the passage of particulates larger than the diameter of the tubular path. 
   Changes in the effective diameter that might otherwise be created by the engagement of the shaft and bore are minimized by creating a press fit of the shaft in the sleeve that induces compressive stress levels higher than the maximum operating pressure (5000 psi), and yet which are below the stress level at which long term creep is significant (as determined by the so-called 1000 hour modulus of the outer tube material). Furthermore, the adjustable device is inherently self-cleaning: contamination in the flow path is flushed out when the restrictor shaft is retracted and the groove is exposed. 
   A further aspect of the invention is a method and apparatus for an adjustable metering valve. Placing a fixed fluid resistor element on the low flow path, and a variable fluid resistor (adjustable metering valve) on a parallel, high flow rate path, the chromatographer can adjust the split flow ratio to virtually any ratio desired. For example, if the user requires nanoliter flow rates, a high fixed resistance cartridge is selected for the low flow rate path that provides a reasonable back pressure at the desired flow rate (say 1000 psi at 100 nanoliters per minute—it is important not to exceed the maximum or minimum pressure limits of the pump). Then the exact desired flow rate through the low flow path is obtained by means of the adjustable resistance valve in the high flow path. When the metering valve is adjusted to 1000 psi back pressure, the resistor chosen in this example will provide exactly 100 nanoliters per minute of flow. Because the volume in the fixed resistor and adjustable resistance valve is negligible compared to the flow rate and residence time in each respective path, the solvent composition and viscosity differences in each path are negligible (less than 1%). 
   Another aspect of the invention is a flow meter that can measure the flow rates on both pathways. A high pressure pump feeds a parallel circuit layout, one branch having fixed resistance, a pressure transducer, and an HPLC analytical column. The other branch includes a fixed resistance, another pressure transducer, and the adjustable resistance valve. Because flow rates are laminar, the flow rate can be determined by measuring the pressure drop across the two fluid resistor elements. The flow meter also allows for the user to know what flow rate is passing through the analytical column without needing to know the resistance of the column. The flow meter also provides a means to document the flow rate during the chromatographic run. This is very important for validating results in drug testing or other critical applications. 
   Accuracy of measurement is not affected by solvent gradient runs. Because the resistor elements each have negligible volume (below 50 nanoliters) the residence time of solvents in each path is too small to permit sufficient change in fluid viscosity to alter measurement accuracy. 
   Another aspect of the invention is the ability to gang multiple controller/meter units together to achieve multi-channel flow splitting. The mass spectrometers that are used with HPLC&#39;s are capable of doing analyses in much less time than the HPLC. So, when combining the output of HPLC to LC-MS, the LC-MS must sit idle while the HPLC completes a run. This is a problem because the mass spectrometer systems typically cost 10 times as much as an HPLC pump and column. Prior art devices use multiple pumps working simultaneously to feed samples through multiple columns for sample separation, and then into the mass spectrometer for final analyses (the mass spec is multiplexed). The present invention allows a single HPLC pump to split flow multiple ways into multiple branches, and then into the mass spectrometer. Each branch includes a pressure transducer, a signal conditioner, and an ADC feeding a digital computing device. The computing device also controls an actuator driver that operates a servo device to selectively vary the variable resistance valve described above. This arrangement provides a great cost savings as well as an important improvement in overall system reliability (an 8 channel system would normally have 32 check valves, 16 high pressure seals, and is very prone to down time). 

   
     BRIEF DESCRIPTION OF THE DRAWING 
       FIG. 1  is a cross-sectional view of the adjustable flow resistance valve of the present invention, shown in the maximum flow resistance disposition. 
       FIG. 2  is a cross-sectional view of the adjustable flow resistance valve of  FIG. 1 , shown in a reduced flow resistance disposition. 
       FIG. 3  is a schematic diagram of the flow metering circuit of the present invention. 
       FIG. 4  is a magnified cross-sectional view of the triangular groove flow path of the adjustable flow resistance valve of the invention. 
       FIG. 5  is a functional block diagram of a multi-channel flow splitting arrangement for a plurality of ganged flow metering circuits. 
   

   DETAILED DESCRIPTION OF THE INVENTION 
   The present invention generally comprises a method and apparatus for controlling and regulating the high pressure, low flow systems used in HPLC and the like. With regard to  FIG. 1 , a major aspect of the invention comprises an adjustable flow rate valve  11  for such high pressure, low flow systems. The valve  11  includes a valve body  12  having a stepped bore  13  extending generally axially therethrough. A sleeve  14  of stainless steel or the like is secured within the bore  13 , and a helical groove  16  is formed in the inner circumferential surface of the sleeve. The axial extent of the helical groove  16  (shown in breakaway in  FIG. 1 ) is substantially the entire length of the sleeve. A restrictor shaft  17  is press fit into the sleeve  14 , the outer surface of the shaft  17  impinging on the inner circumferential surface of the sleeve and sealing the helical groove  16  to define an enclosed helical capillary fluid flow path through the groove  16 . The length of the flow path may be many times larger than the length of the sleeve  14 , and the long path tends to negate any variations in effective diameter over the length of the flow path. An extension  18  of the shaft  17  extends outwardly therefrom, and is provided with indicia that indicate a liquid flow ratio, as will be described in the following. High pressure seal assemblies  19  and  21  are secured at opposed ends of the sleeve  14  to contain the high pressure liquid fed through the device. 
   A high pressure input fitting  22  is secured in the valve body  12 , and is connected through a small passage  23  to a flow space at the inner end of the helical groove  16 . Another high pressure input fitting  26  is secured to the body  12 , and a fixed flow resistance cartridge  27  is incorporated within the fitting  26 . The fitting  26  communicates through passage  24  to the flow space at the inner end of the groove  16 . This arrangement permits high pressure liquid to be input through fitting  22 , the liquid flow being split so that some of the flow proceeds through groove  16  and the remainder of the flow goes through passage  26  and fixed flow resistance  27  to a low flow output branch, as will be described further below. 
   The fluid resistance of the flow path through groove  16  is selected by adjusting the length of the flow path. This is accomplished by changing the length of engagement of the restrictor shaft  17  with the helical flow path  16 . Secured to body  12  is a valve body extension  42 , which includes a central bore  43  aligned with bore  13 . Restrictor shaft  17  includes a head  44  that is secured within a drive block  46 , and block  46  is axially translatable within bore  43 . Block  46  is provided with a longitudinally extending groove  47 , and pin  48  extends from component  42  to the groove  47  to prevent rotation of block  46 . Shaft  49  extends axially from block  46 , and is provided with fine drive threads  51 . 
   A cap assembly  52  is secured coaxially to the extension  42 , and supports a rotatable collar  53  that has internal threads adapted to engage drive threads  51 . Adjustment knob  54  is secured about the cap assembly  52 , and pin  56  joins the knob to the collar  53  for rotation in common. Thus the knob may be rotated to turn the collar  53  so that the threads  51  move the drive block axially and translate the restrictor shaft axially.  FIG. 2  depicts the device  11  with the restrictor shaft  17  translated partially outwardly (to the right in  FIG. 2 ) so that a portion of the helical groove  16  is unsealed, reducing the length of the capillary flow path so that the fluid flow resistance is reduced concomitantly. It may be appreciated that the knob  54  may be replaced by a motorized rotational drive, such as a stepper motor, for automated flow adjustment. 
   The restrictor shaft  17  is preferably formed of a ceramic material so that the press fit thereof into the sleeve  14  does not create spalling or other surface disruptions that could introduce contamination and particulate debris into the flow stream. 
   The fixed fluid flow resistance  27  may comprise any convenient construction known in the prior art. One preferred embodiment may comprise a helical groove formed in the receptacle that receives the cartridge  27 , the cartridge  27  serving to seal the helical groove and form a helical capillary flow path in a fashion similar to the components  14 ,  16 , and  17 , although the non-movable cartridge  27  defines a fixed, non-adjustable flow path having a fixed resistance. A number of fittings  26  may be provided, each having a cartridge  27  with a different known fluid flow resistance, whereby fittings  26  may be interchanged to selectively modify the fixed resistance and the low flow output. 
   With regard to  FIG. 4 , the groove  16  in the sleeve  14  is defined by a 60° equilateral triangle. The groove has a flow resistance approximately the same as a capillary tube  61  having a diameter that fits within the 60° triangle, yet the triangular configuration has the advantage of permitting the passage of particulates, such as oblong particle  62 , that are larger than the diameter of the tubular capillary  61 . Thus clogging of the flow path is minimized. The hydraulic radius of a triangular groove is given by the relationship: 
   
     
       
         
           
             Hydraulic  radius 
           
           = 
           
             
               (cross  sectional  area) 
             
             
               (wetted  perimeter) 
             
           
         
       
     
     
       
         
           
             Area  of  triangular  groove 
           
           = 
           
             
               Base 
               × 
               Height 
             
             2 
           
         
       
     
     
       
         
           
             Wetted  perimeter 
           
           = 
           
             3 
             × 
             Base 
           
         
       
     
     
       
         
           
             Hydraulic  radius 
           
           = 
           
             h 
             / 
             6 
           
         
       
     
   
   The equivalent diameter of a circular groove=4×hydraulic radius or 2h/3. A conduit of circular cross section h would provide the same pressure drop as a 60° triangular groove of depth=1.5 h. Therefore, since most particles have irregular shapes, there is less chance for clogging to occur in the 60° triangular groove. 
   Another salient feature of the invention is a flow meter that can be employed to adjust and measure the flow rates in a HPLC arrangement. With regard to  FIG. 3 , a high pressure pump  63  delivers a flow Q to two parallel branches  64  and  66 . Branch  64 , a low flow path, is comprised of a fluid resistance R 1  having a flow q 1  therethrough and a pressure drop P 1 , which is connected to the analytical column having an unknown flow resistance R c . Branch  66 , a high flow path, is comprised of a fluid resistance R 2  having a flow q 2  therethrough and a pressure drop P 2 , which is connected to the adjustable flow resistance R v  of the device  11  described above. R 1  may comprise the fixed, known flow resistance of cartridge  27  of the device  11 . The following relationships pertain to the calculation of flow rate through the column: 
           Q   =       q   1     +     q   2                     q   1     =       (     P   -     P   1       )       μ   ⁢           ⁢     R   1                       q   2     =       (     P   -     P   2       )       μ   ⁢           ⁢     R   2                       q   1     =           R   2     ⁡     (     P   -     P   2       )       ⁢   Q           R   1     ⁡     (     P   -     P   2       )       +       R   2     ⁡     (     P   -     P   1       )                 
It is apparent that viscosity is not a factor in calculating the flow rates, and a process monitoring device may be easily programmed to calculate the flow rates in real time based on measured parameters P, P 1  and P 2 . The flow meter also allows for the user to know what flow rate is passing through the analytical column without needing to know the resistance of the column. The flow meter also provides a means to document the flow rate during a chromatographic run.
 
   Another salient feature of the present invention is that it allows a single HPLC pump to split flow multiple ways into multiple branches, and then into the mass spectrometer. With regard to  FIG. 5 , each branch includes a pressure transducer  71 , a signal conditioner  72 , and an A/D converter  73  feeding a digital computing device  74 . The computing device  74  is programmed to control an actuator driver  76  that operates a servo device  77  (such as a stepper motor  80 ) to selectively vary the variable resistance valve  11  described above. A status display  78  and an interface  79  to an external computer for data collection and monitoring may also be provided. This arrangement provides a great cost savings as well as an important improvement in overall system reliability. 
   The foregoing description of the preferred embodiment of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and many modifications and variations are possible in light of the above teaching without deviating from the spirit and the scope of the invention. The embodiment described is selected to best explain the principles of the invention and its practical application to thereby enable others skilled in the art to best utilize the invention in various embodiments and with various modifications as suited to the particular purpose contemplated. It is intended that the scope of the invention be defined by the claims appended hereto.