Abstract:
A combined pump-injector valve system utilizing a monolithic body to provide the barrel of the pump and as the stator of the valve, thus eliminating any need for connections between a pump and a valve, and therefore the potential for high-pressure leaks or pressure reductions. The combined pump-injector valve permits injection of nanoliter-sized samples into a chromatographic column, which is sealed during loading of the sample and filling of the pump, such that complete analyses can be completed with microliters of mobile phase with nanoliters of a sample. The pump-injector valve system further includes a pressure sensor external the barrel of the pump and may include an interim position intermediate loading and injection where the contents of the barrel may be pressurized to a desired pressure.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part and claims the benefit of U.S. Non-Provisional patent application Ser. No. 14/333,661 entitled “Pump and injector for liquid chromatography” filed Jul. 14, 2014 and of U.S. Non-Provisional patent application Ser. No. 14/156,197 entitled “Pump and injector for liquid chromatography” filed on Jan. 15, 2014, which claim the benefit of U.S. Provisional Patent Application No. 61/753,299 entitled “Integral nano-scale pump and injector for high performance liquid chromatography” filed on Jan. 16, 2013 in the United States Patent and Trademark Office, and which are incorporated herein by reference. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not Applicable. 
     BACKGROUND OF THE INVENTION 
     1. Field of Invention 
     The present invention pertains to pump and injection valve systems for use with liquid chromatography. More particularly, the present invention pertains to a combined pump/injection valve for injection of a nanoliter-sized sample into a chromatography column utilizing an single piece as the barrel of the pump and as the stator of the valve, thus eliminating any need for connections between the pump and valve. 
     2. Description of the Related Art 
     High performance liquid chromatography (HPLC) is generally performed using pumps, columns and injection valves scaled to deliver fluids at flow rates measured in cubic centimeters of fluid per minute. These components are typically separate and joined together to provide a system for HPLC. Unfortunately, these systems require relatively large sample volumes, large mobile phases, and large flow rates for analysis. 
     Additionally, these relatively large systems frustrate generate of field portable HPLC units, where there is a need for a lightweight robust flow system which uses a minimum of mobile phase during an analysis. 
     It would therefore be desirable to provide an integrated nano-scale pump and injection valve for high performance liquid chromatography. 
     SUMMARY OF THE INVENTION 
     The present invention therefore meets the above needs and overcomes one or more deficiencies in the prior art by providing a combined pump/injector valve which injects nanoliter samples into a chromatographic column, which is sealed during loading of the sample and filling of the pump, such that complete analyses can be completed with microliters of mobile phase, ranging from as small as about 5-10 nanoliters, to 60 nanoliters, and larger. The present invention therefore provides a lightweight robust flow system which uses a minimum of mobile phase during an analysis and is appropriate for use as a field portable HPLC unit. 
     The present invention provides an integral nano-scale pump and injection valve for high performance liquid chromatography which includes an integrated barrel-stator, which has an elongate barrel in a first end and a stator at a second end, a plunger slidably disposed within an interior chamber of the barrell of substantially uniform cross-section, and a rotor, wherein the pump and injection valve is switchable between a load position and a injection position. In one embodiment, the circular rotor has a surface adjacent the stator and has a plurality of channels in its surface and is with respect to the stator about a centerpoint between the load position and the injection position. The elongate barrel portion of the integrated barrel-stator includes an open ends, a length, and a sidewall defining the interior chamber adapted to receive a supply of fluid, an outer diameter, and a wall thickness. The circular stator has an orifice therethrough at its centerpoint and a first side and a second side such that the elongate barrel open distal end is aligned with the second side of the stator at the centerpoint and the interior chamber includes the orifice. The pump is therefore in communication with the valve at the orifice. 
     In a first embodiment, the rotor includes three channels and the stator has a first stator port for communication with a mobile phase supply, a second stator port in communication with a fifth stator port, a third stator port for communication with a sample reservoir, a fourth stator port for sample outflow, a sixth stator port for communication with a chromatography column, a seventh stator port for return from the chromatography column, and an eighth stator port for outflow from the valve. In the first embodiment, the load position is defined by the first port and the orifice communicating with a first channel and by the third port and the fourth port communicating with a second channel. In the first embodiment, the injection position is defined by the orifice and the second port communicating with the first channel, by the fifth port and the sixth port communicating with the second channel, and by the seventh port and the eighth port communicating with the third channel. 
     In the alternative embodiment, the rotor includes four channels and the stator has a first stator port for communication with a mobile phase supply, a second stator port in communication with a fifth stator port via an external loop, a third stator port for communication with a sample reservoir, a fourth stator port for sample outflow, a sixth stator port for communication with a chromatography column, a seventh stator port for return from the chromatography column, and an eighth stator port for outflow from the valve. In the alternative embodiment, the load position is defined by the first port and the orifice communicating with a first channel, by the second port and the third port communicating with the second channel, and the fourth port and the fifth port communicating with the third channel. In the alternative embodiment, the injection position is defined by the orifice and the second port communicating with the first channel, by the fifth port and the sixth port communicating with the third channel, and by the seventh port and the eighth port communicating with the fourth channel. 
     In a further alternative embodiment, where the embodiment is used as a pump without regard to the equipment connected thereto, the rotor has only one channel and the stator has a first stator port for communication with a mobile phase supply and a second stator port for communication with an external device. In the further alternative embodiment, the load position is defined by the first port and the orifice communicating with a first channel and the injection position is defined by the orifice and the second port communicating with the first channel. 
     In an additional alternative embodiment, wherein the embodiment is used to push sample through a column, but wherein the output of the column is provided to other equipment rather than through the valve, the embodiment includes channels and the stator has a first stator port for communication with a mobile phase supply, a second stator port in communication with a fifth stator port via an external loop, a third stator port for communication with a sample reservoir, a fourth stator port for sample outflow, and a sixth stator port for communication with a chromatography column. In the additional alternative embodiment, the load position is defined by the first port and the orifice communicating with a first channel, by the second port and the third port communicating with the second channel, and the fourth port and the fifth port communicating with the third channel. In the alternative embodiment, the injection position is defined by the orifice and the second port communicating with the first channel, and by the fifth port and the sixth port communicating with the third channel. 
     In each embodiment, it may be advantageous to determine the pressure within the barrel and even to provide an interim position between the load position and the injection position, which may be characterized as a dead or pressuring position, which has no connectivity and thus permits the fluid received in the load position to be pressurized to a desired pressure. 
     Additional aspects, advantages, and embodiments of the invention will become apparent to those skilled in the art from the following description of the various embodiments and related drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       So that the manner in which the described features, advantages, and objects of the invention, as well as others which will become apparent; are attained and can be understood in detail; more particular description of the invention briefly summarized above may be had by referring to the embodiments thereof that are illustrated in the drawings, which drawings form a part of this specification. It is to be noted, however, that the appended drawings illustrate only typical preferred embodiments of the invention and are therefore not to be considered limiting of its scope as the invention may admit to other equally effective embodiments. 
       In the drawings: 
         FIG. 1  is an illustration of a top view of one embodiment of the present invention as assembled. 
         FIG. 2  is an illustration of a side view of one embodiment of the present invention as assembled. 
         FIG. 3  is an illustration of the face of the stator of the integrated barrel-stator of the first embodiment of the present invention. 
         FIG. 4  is an illustration of the face of the rotor of the first embodiment of the present invention. 
         FIG. 5  is an illustration of the relative positions of the face of the stator and the face of the rotor of the first embodiment of the present invention in the load position. 
         FIG. 6  is an illustration of the relative positions of the face of the stator and the face of the rotor of the first embodiment of the present invention in the injection position. 
         FIG. 7  is a cross-section illustration of the present invention along line Z-Z of  FIG. 1  for the maximum position of the pump associated with the load position in connection with a linear actuator. 
         FIG. 8  is a cross-section illustration of the present invention along line Z-Z of  FIG. 1  for the maximum position of the pump in the injection position in connection with a linear actuator. 
         FIG. 9  is a close-up of the pump plunger driven forward for delivery for the maximum position of the pump in the injection position. 
         FIG. 10  is an illustration of isometric view of the embodiment of the present invention with the pump and valve actuators illustrating the first valve position illustrated in  FIGS. 5 and 7  at the maximum position of the pump in the load position. 
         FIG. 11  is an illustration of isometric view of the embodiment of the present invention with the pump and valve actuators illustrating the second valve position illustrated in  FIGS. 6 and 8  at the maximum position of the pump in the injection position. 
         FIG. 12A  is an enlargement of Section A of  FIG. 10 . 
         FIG. 12B  is an enlargement of Section B of  FIG. 11 . 
         FIG. 13  is an illustration of the face of the stator of the integrated barrel-stator in the alternative embodiment of the present invention. 
         FIG. 14  is an illustration of the face of the rotor of the alternative embodiment of the present invention. 
         FIG. 15  is an illustration of the relative positions of the face of the stator and the face of the rotor of the alternative embodiment of the present invention in the load position. 
         FIG. 16  is an illustration of the relative positions of the face of the rotor and the face of the rotor of the alternative embodiment of the present invention in the injection position. 
         FIG. 17  is an illustration of the relative positions of the face of the stator and the face of the rotor of the further alternative embodiment of the present invention in the load position. 
         FIG. 18  is an illustration of the relative positions of the face of the rotor and the face of the rotor of the further alternative embodiment of the present invention in the injection position. 
         FIG. 19  is an illustration of the relative positions of the face of the stator and the face of the rotor of the additional alternative embodiment of the present invention in the load position. 
         FIG. 20  is an illustration of the relative positions of the face of the rotor and the face of the rotor of the additional alternative embodiment of the present invention in the injection position. 
         FIG. 21  is a close-up of the pump plunger driven forward for delivery for the maximum position of the pump in the injection position depicting a seal of the present disclosure. 
         FIG. 22  is an illustration of the relative positions of the face of the stator and the face of the rotor of the additional alternative embodiment of the present invention in the load position. 
         FIG. 23  is an illustration of the relative positions of the face of the stator and the face of the rotor of the additional alternative embodiment of the present invention in the injection position. 
         FIG. 24  is an illustration of a strain gauge, as a pressure sensor, incorporated about the integrated barrel-stator. 
         FIG. 25  is an illustration of the face of the rotor of the present invention identifying the location of the interim position. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Referring to  FIGS. 1 and 2 , a two-position embodiment of the integrated nano-scale pump and injection valve  100  is provided. A top view of one embodiment of the integrated nano-scale pump and injection valve  100  as assembled is provided in  FIG. 1  while a side view is provided  FIG. 2 . As illustrated in  FIGS. 1B and 2 , the integrated nano-scale pump and injection valve  100  includes an integrated barrel-stator  716  which provides the interface between the pump section  102  and valve section  104 . 
     Referring to  FIGS. 3 and 4 , constructions of the face of the stator  302  and the face of the rotor  402  of the integrated barrel-stator  716  are illustrated for a first embodiment. Referring to  FIGS. 13 and 14 , constructions of the face of the stator  302  of the integrated barrel-stator  716  and the face of the rotor  1402  of the valve section  104  are illustrated for an alternative embodiment. 
     Referring to  FIGS. 1-22 , by forming the elongate barrel  726  of the pump  708  and the stator  302 ,  1302 ,  1712 ,  1932  of the valve  710  of a single part as integrated barrel-stator  716 , the integrated nano-scale pump and injection valve  100  may operate at high pressures without degradation incident to intervening parts and fittings. 
     Unlike the prior art where a valve and pump were separate bodies simply joined together, in the integrated nano-scale pump and injection valve  100 , as illustrated in  FIGS. 7-12B , the elongate barrel  726  of the pump  708  and the stator  302 ,  1302 ,  1712 ,  1932  of the valve  710  are integrally formed of a single piece, i.e a monolithic body, to provide direct communication between the pump  708  and the valve  710  without introducing any fittings or connectors which may swell or leak during high pressure operation. 
     By switching between the maximum extent of the load position  502 ,  1502 ,  1710 ,  1928  and the maximum extent of the injection position  602 ,  1602 ,  1802 ,  2002 , the integrated nano-scale pump and injection valve  100  provides a pump  708 , which may be sized to hold microliters for use with nano-scale columns for quick separation. 
     Upon initiation of loading, the pump  708  and valve  710  and positioned in the load position  502  and the plunger  706  begins being retracting by the piston  712  and draws a solvent from a reservoir, such as through a 15 cm×200 μm steel tube into the barrel  726 . At the same time and independent of pump filling, a sample is introduced into the sample loop through a 5.08 cm×75 μm inner diameter capillary, which is connected to the port  308  on the pump and to a sample supply, preferably using a zero-dead volume connector. 
     After completion of loading, the integrated nano-scale pump and injection valve  100  may be switched for injection, changing the direction of operation of the pump  708  and changing the position of the valve  710 . During injection, the plunger  706  is driven by the piston  712  into the barrel  726 . The rate of advance, and therefore the dispensing flow rate, may be controlled by power supply and/or by computer software. As the plunger  706  is driven forward by the piston  712 , the sample is driven from the sample passage of second channel  406  into the column  504  while the mobile phase flows from the barrel  726  through the loop  506 , through the column  504  and to the detector. 
     In all embodiments, in the load position  502 ,  1502 ,  1710 ,  1928 , the pump plunger  706  is retracted for filling the interior chamber  702  as illustrated in  FIGS. 7, 10 and 12A . The plunger may have a diameter of 0.03 inches, or slightly smaller, or of 0.93 inches, or slightly larger, or may be between, such as 0.62 inches. The pump  708  thus includes a pump plunger  706 , an interior chamber  702  defined by an elongate barrel  726  and the plunger  706 . Referring to  FIGS. 5, 7, 10, 12A and 15 , the arrangement and nano-scale operation of integrated nano-scale pump and injection valve  100  is illustrated in at the maximum position of the pump  708  in the load position  502 . The load position  502  of integrated nano-scale pump and injection valve  100 , showing the positions of the stator  302  and the rotor  402  in the first embodiment, is depicted in  FIG. 5 . The load position  1502  of integrated nano-scale pump and injection valve  100 , showing the positions of the stator  1302  and the rotor  1402  for the alternative embodiment is depicted in  FIG. 15 . As can be appreciated either the stator  302 ,  1302 ,  1712 ,  1932  or the rotor  402 ,  1402 ,  1702 ,  1902  will include a seal surface to contact the other. A cross-section illustration of the present invention along line Z-Z of  FIG. 1  for the maximum position of the pump  708  in the load position  502 ,  1502 ,  1710 ,  1928  is illustrated in  FIG. 7 . An illustration of isometric view of the embodiment of the present invention with the valve actuator illustrating the first valve position is illustrated in  FIG. 10 . An enlargement of Section A of  FIG. 10  is provided in  FIG. 12A . 
     Referring to  FIG. 21 , for operation at high pressure, such as above 10000 psi, it is essential that a strong seal  2150  be positioned about the plunger  706  within the barrel  726  of the integrated barrel-stator  716 , at least a stroke-length  1202  above or beyond the first end  750  of the plunger  706  when in the maximum injection position so as to contact the plunger  706  and to form a seal thereabout. Positioning the seal  2150  less than a stroke-length  1202  from the first end  750  of the plunger  706  would cause the seal  2150  to fail when the plunger  706  was fully retracted to reach the maximum load position. While a single seal across the barrel  726 , through which the plunger  706  would move, may be used, a composite seal is preferable. As depicted in  FIG. 21 , the seal  2150  about the plunger  706  within the barrel  726  may be formed of a compressed sequence of a first hard seal  2100 , a flexible seal  2108 , and a second hard seal  2112 , placed under compression by a driving disk  2106  maintained within the integrated barrel-stator  716 . The diameter of the barrel  726  of the integrated barrel-stator  716  is enlarged for that section more than a stroke-length  1202  above or beyond the first end  750  of the plunger  706  when in the maximum injection position to accept a first hard plastic seal  2100 . The first hard plastic seal  2100  may be composed of a material such as polyether ether ketone (PEEK) or another material, and is sized to fit within the barrel  726  and about the plunger  706  without precluding movement of the plunger  706 . Atop the first hard plastic seal  2100  is positioned a flexible seal  2108 . The flexible seal  2108  is composed of a compressible sealing material, such as polytetrafluoroethylene (PTFE). The flexible seal  2108  is sized to fit within the barrel  726  and about the plunger  706  without precluding movement of the plunger  706 . Atop the flexible seal  2108  is positioned a second hard plastic seal  2112 , which may also may be composed of a material such as polyether ether ketone (PEEK) or another material, and is sized to fit within the barrel  726  and about the plunger  706  without precluding movement of the plunger  706 . Compression of the flexible seal  2108  results in lateral expansion of the flexible seal  2108  and thereby causes the flexible seal  2108  to provide a seal against the plunger  706  which does not preclude movement of the plunger  706 , between the first hard seal  2100  and the second hard seal  2112 . This may be accomplished by application of force against the second hard seal  2112  and a shoulder  2114  in the barrel  726  to maintain the position of the first hard seal  2100 . The application of force against the second hard seal  2112  may be obtained by joining a threaded male sleeve or nut  2102 , having a bore therethrough to freely accommodate the plunger  706  and piston  712  without interference, to the integrated barrel-stator  716 , above or beyond the seal  2150 , which threaded male sleeve  2102  would apply force to one or more springs  2122 , particularly a Belleville spring also known as a coned disc spring, positioned within the integrated barrel-stator  716  above or adjacent the barrel  726 , to force a driving disk  2106  to compress the second hard seal  2112 . The threaded male sleeve  2102  is sized to a threaded female section of the integrated barrel-stator  716  above or adjacent the barrel  726 . The driving disk  2106  includes a bore  2124  sized to permit the plunger  706  to pass therethrough without interference, a shoulder  2116  to permit the application of force against the driving disk  2106  from the springs  2122  smaller in diameter than the threaded male sleeve or nut  2102  so as not to contact the inner walls of the integrated barrel-stator  716 , and a neck  2120  at its end  2126  proximate the barrel  726  sized to enter the barrel  726  without interference and having sufficient height to contact and apply force against the second hard seal  2112 . As a result, the neck  2120  is driven against the second hard seal  2112 , which is in turn driven into the flexible seal  2108  to compress it and form a seal about the plunger  706 . The plunger  706  is therefore able to move through the seal  2150  without fluid seeping past, even as the flexible seal  2108  may become pliable during repeated movement of the plunger  706 . Because only the seals  2112 ,  2108 ,  2100  laterally contact the plunger  706 , and because the balance of the components, including the integrated barrel-stator  716 , the threaded male nut or sleeve  2102 , and the driving disk  2106 , include sufficient clearance for the plunger  706  to move without interference, the plunger  706  can move within the barrel  726  and can operate to draw or eject fluid into the barrel  726  and through the stator  302 , particularly at high pressure. 
     Thus, the seal  2150  includes a first hard plastic seal  2100 , a flexible seal  2108 , a second hard plastic seal  2112  and is compressed to seal about the plunger  706  by a driving disk  2106 , a threaded male sleeve  2102 , and one or more springs  2122 . The first hard plastic seal  2100  is sized to fit within the barrel  726  and to fit about the plunger  706 . The flexible seal  2108  is sized to fit within the barrel  726  and to fit about the plunger  706  adjacent the first hard plastic seal  2100 . The second hard plastic seal  2112  is sized to fit within the barrel  726  and to fit about the plunger  706  adjacent the flexible seal  2108 . The driving disk  2106  has a bore  2124  therethrough sized to fit about the plunger  706  without interference, a first end  2118  and a second end  2126 . The driving disk  2106  is sized to freely fit within said integrated barrel-stator  716  adjacent the barrel  726 , and includes a shoulder  2116  near the first end  2118 , and a neck  2120  at the second end  2126 , which neck  2120  is sized to fit within the barrel  726  and to contact the first hard plastic seal  2100 . The threaded male sleeve  2102  has a bore therethrough sized to permit movement of the plunger  706  without interference and is sized to a threaded female section within the integrated barrel-stator  716  above, or adjacent, the barrel  726 . The spring  2122  contacts the shoulder  2116  of the driving disk  2106  and an end of said threaded male sleeve  2102  and is compressed as the threaded male sleeve  2102  is driven into the integrated barrel-stator  716 . 
     Referring to  FIG. 5 , in the first embodiment, the valve  710  thus has a circular stator  302 , formed integrally with the elongate barrel  726  of a single block of monolithic material, to provide the integrated barrel-stator  716 , and a circular rotor  402  where the two components cooperate to permit or preclude fluid communication among various parts of the valve  710 . The stator  302  has an orifice  320  at its centerpoint, as well as a first stator port  304  for communication with a mobile phase supply, a second stator port  306  in communication with a fifth stator port  312 , a third stator port  308  for communication with a sample reservoir, a fourth stator port  310  for outflow of sample waste, a sixth stator port  314  for communication with a chromatography column  504 , a seventh stator port  316  for return from the chromatography column  504 , and an eighth stator port  318  for outflow from the valve  710  such as to a detector. As both ends of the column  504  can be connected to the integrated nano-scale pump and injection valve  100  to maintain pressure during filling of the integrated nano-scale pump and injection valve  100  when the flow through the column  504  is stopped, if desired. This would eliminate a delay period for column re-pressurization. The rotor  402  therefore has a surface adjacent the stator  302  and three channels, or slots,  404 ,  406 ,  408  in its surface. The rotor  402  is rotatable with respect to the stator  302  about the centerpoint between the load position  502  and the injection position  602 . Rotation between the two positions may be 45 degrees about the centerpoint, or more or less. In the load position  502 , components are isolated while the mobile phase is delivered to the internal chamber  702  of the pump  708 , so that the first port  304  communicates with the orifice  320 , and thereby to the internal chamber  702  of the pump  708 , via the first channel  404 , to provide filling, while all other ports are individually or paired in isolation, include the third port  308  and the fourth port  310 , while communicating via the second channel  406  not otherwise communicating with any other components. The column  504  may therefore maintained at pressure and isolated while the interior chamber  702  of the pump  708  located in the pump section  102 , as illustrated in  FIG. 7 , is filled by a mobile phase by drawing mobile phase through orifice  320 , introduced via first channel  404  which is connected to port  304 . For initial charging of the column  504 , the operator can run the mobile phase through the second channel  406 , the sample channel, switching between the load position  502  and the injection position  602  to fill the column  504  and to ensure no bubbles are present in the system. In the load position  502 , the port  318 , which may be connected to a detector, is likewise isolated. Referring to  FIGS. 3 and 4 , and more particularly to  FIG. 5 , in this load position  502 , with reference to stator  302  and rotor  402 , ports  306  and  312  are in communication to form a loop  506 , to provide an internal sample, but are otherwise isolated. This loop  506  may be of 5.08 cm×75 or 150 μm inner diameter stainless steel tubing to carry the mobile phase to the column during injection (dispensing). A sample is introduced to and flows through the integrated nano-scale pump and injection valve  100  at port  308 , the sample inlet port, which is connected via second channel  406  to port  310 , the waste outlet port. As can be appreciated each port is associated with a connector  206  on the intersection of the pump section  102  and the valve section  104 . During the introduction of the sample, second channel  406  therefore contains the sample to be tested. Thus, in this load position  502 , a sample, which may originate from an external reservoir, may be flowed through an internal passage. In the injection position  602 , mobile phase is delivered from the pump  708  and directed through the valve  710  to the column  504  and potentially to a downstream detector by connecting the orifice  320 , which is in communication with the pump  708 , and the second port  306  via the first channel  404 , by connecting the fifth port  312  and the sixth port  314  via the second channel  406 , which thereby provides a complete flow path to the chromatography column  504 , and by connecting the seventh port  316 , which is in communication with the outflow of the column  504 , with the eighth port  318  via the third channel  408  so that the sample separated by the column  504  may be processed by a detector. As can be appreciated, in a secondary embodiment, the seventh port  316 , the eighth port  318  and the third channel  408  could be omitted and the outflow from the column  504  provided directly to a detector or other equipment. 
     Due to the volumes involved, refilling of the integrated nano-scale pump and injection valve  100  may be accomplished is less than 2 minutes. Since typical flow rates used in capillary columns (100-150 μm i.d.) range from 100 to 500 nL/min, an isocratic separation can be easily completed without the need to refill the integrated nano-scale pump and injection valve  100 . 
     In the alternative embodiment, such as depicted in  FIGS. 13, 14, 15, and 16 , the valve  710  has a circular stator  302 , again of a single block of monolithic material to also provide the elongate barrel  726 , formed integrally therewith, and a circular rotor  402  where the two components cooperate to permit or preclude fluid communication among various parts of the valve. As with the stator of the first embodiment, the stator  1302  has an orifice  1320  at its centerpoint with the pump  708  in communication with the valve  710  at the orifice  1320 , a first stator port  1304  for communication with a mobile phase supply, a second stator port  1306  in communication with a fifth stator port  1312  via a loop  1506 , a third stator port  1308  for communication with a sample reservoir, a fourth stator port  1310  for outflow, a sixth stator port  1314  for communication with a chromatography column  1504 , a seventh stator port  1316  for return from the chromatography column  1504 , and an eighth stator port  1318  for outflow from the valve  710  such as to a detector. The rotor in the alternative embodiment includes the four channels  1404 ,  1406 ,  1408 ,  1410  in its surface. In the alternative embodiment, the load position  1502  is defined by the first port  1304  and the orifice  1320  communicating with the first channel  1404 , by the second port  1306  and the third port  1308  communicating with the second channel  1406 , and the fourth port  1310  and the fifth port  1312  communicating with the third channel  1408 . In the alternative embodiment, as illustrated in  FIG. 15 , the column  504  is attached to port  1314 , column inflow, and port  1316 , column outflow, which are otherwise isolated. The column  1504  is therefore maintained at pressure and isolated while the interior chamber  702  of the pump  708  located in the pump section  102 , as illustrated in  FIG. 7 , is filled by a mobile phase by drawing mobile phase through orifice  1320 , introduced via the first channel  1404 , the fill/dispense channel, which is connected to port  1304 . In the load position  502 , the port  318 , which may be connected to a detector, is likewise isolated. Referring to  FIGS. 13 and 14 , and more particularly to  FIG. 15 , in this load position  502 , with reference to stator  1302  and rotor  1402 , ports  1306  and  1312  are in communication to form a loop  1506  but are otherwise isolated. A sample is introduced to and flows through the integrated nano-scale pump and injection valve  100  at port  1308 , the sample inlet port, which is connected via second channel  1406  to port  1306  and then, via a loop  1506  to port  1312 , which is then in communication with port  1310  via third channel  1408 , the waste outlet port. As can be appreciated each port is associated with a connector  206 . During the introduction of the sample, the sample to be tested is contained with the channel  1406  and the loop  506 , providing for an increased sample size. Thus, in this load position  502 , a sample, which may originate from an external reservoir, may be flowed through an internal passage. In the alternative embodiment, the injection position  1602  is defined by the orifice  1320  and the second port  1306  communicating with the first channel  1404 , by the fifth port  1312  and the sixth port  1314  communicating with the third channel  1408 , and by the seventh port  1316  and the eighth port  1318  communicating with the fourth channel  1410 . 
     In the first embodiment, the second channel  406  defines the nano-scale sample size while the interior chamber  702  contains the volume from which mobile phase is pumped. In the alternative embodiment, the third channel  1408  and the loop  1506  define the nano-scale sample size. 
     Referring to  FIGS. 6, 8, 9, 11, and 12B , the nano-scale operation of the pump section  102  is illustrated in the injection position  602  for the first embodiment. The injection position  602  of the nano-scale operation of the pump section  102 , showing the positions of the stator  302  and the rotor  402 , is depicted in  FIG. 6 . As illustrated in  FIG. 6 , the rotor is rotated 45 degrees, preferably by a mechanical valve actuator  202  coupled to act in concert with the action of the linear pump actuator  204 , generating a new flow path within the valve  710 . The relative position between the stator  302  and the rotor  402  may be set to provide for a greater or lesser rotation. Referring to  FIG. 6 , the first channel  404 , the fill/dispense channel, connects the internal pump  708 , via orifice  320 , to the loop  506  at port  312 . The loop  506  now connects to second channel  406  containing the sample. Ports  308  and  310  are now isolated, preventing further inflow of any sample. Similarly, port  304  is isolated, preventing further inflow of mobile phase. As second channel  406  containing the sample now connects to the inlet of the column  504  via port  314  and as channel  408  now connects the outlet of the column  504 , at port  316 , to the port  318 , the outlet to the detector, a complete flow path is established and the mobile phase pushes the sample through the column  504  and to any connected detector. This is accomplished by the pump plunger  706  being driven toward the valve  710  as illustrated in  FIGS. 8, 10 and 12B , displacing fluid from the interior chamber  702  into the valve  710 . Thus, the pump  708  delivers fluid through the sample passage of second channel  406  into the column  504 . When the drive shaft  730  of the valve  710  is rotated by a valve actuator  202 , the pump  708  is started, which results in the pump  708  starting the moment the endpoint is reached and thus avoids the column bed becoming unstable. As can be appreciated, upon completion of the analysis, the integrated nano-scale pump and injection valve  100  is returned to the load position  502 , the filling position. 
     Referring to  FIGS. 8, 9, 11, 12B, and 16 , the nano-scale operation of the pump section  102  is illustrated in the injection position  1602  for the second embodiment. The injection position  1602  of the nano-scale operation of the pump section  102 , showing the positions of the stator  1302  and the rotor  1402 , is depicted in  FIG. 16 . As illustrated in  FIG. 16 , the rotor is rotated 45 degrees, preferably by a mechanical valve actuator  202  coupled to act in concert with the action of the linear pump actuator  204 , generating a new flow path within the valve  710 . The relative position between the stator  1302  and the rotor  1402  may be set to provide for a greater or lesser rotation. Referring to  FIG. 16 , first channel  1404 , the fill/dispense channel, connects the internal pump  708 , via orifice  1320 , to the loop  1506  at port  1312 . The loop  1506 , containing some sample, connected to third channel  1408  also containing some sample, now connects to the inlet of the column  1504  via port  1314  and as third channel  1408  now connects the outlet of the column  1504 , at port  1316 , to the port  1318 , the outlet to the detector, a complete flow path is established and the mobile phase pushes the sample through the column  1504  and to any connected detector. This is accomplished by the pump plunger  706  being driven toward the valve  710  as illustrated in  FIGS. 8, 10 and 12B , displacing fluid from the interior chamber  702  into the valve  710 . Thus, the pump  708  delivers fluid into the column  504 . Ports  1308  and  1310  are isolated, preventing further inflow of any sample. Similarly, port  1304  is isolated, preventing further inflow of mobile phase. When the drive shaft  730  of the valve  710  is rotated by a valve actuator  202 , the pump  708  is started, which results in the pump  708  starting the moment the endpoint is reached and thus avoids the column bed becoming unstable. As can be appreciated, upon completion of the analysis, the integrated nano-scale pump and injection valve  100  is returned to the load position  502 , the filling position. 
     Referring to  FIGS. 17 and 18 , the present disclosure may alternatively be used as a pump without regard to the equipment connected thereto. In the further alternative embodiment, the rotor  1702  has a channel  1704  and the stator  1712  has a first stator port  1706  for communication with a mobile phase supply, an orifice  1714  in communication with the elongate barrel  726  and a second stator port  1708  for communication with an external device. In the further alternative embodiment, the load position  1710 , as illustrated in  FIG. 17 , is defined by the first port  1706  and the orifice  1714  communicating with the channel  1704  and the injection position  1802  is defined by the orifice  1714  and the second port  1708  communicating with the channel  1704 . As can be appreciated, any number of additional ports may be positioned on the stator  1712  to permit the pump to draw fluid through the first port  1706  to be pumped to any one of a plurality of ports, providing a multiple position valve. 
     Referring to  FIGS. 19 and 20 , the present disclosure may be used to push a sample through a column, wherein the output of the column is provided to other equipment rather than through the valve. In the additional alternative embodiment, the rotor  1902  has a first channel  1904 , a second channel  1906 , and a third channel  1926 , and the stator  1932  has the orifice  1924  in communication with the elongate barrel  726 , a first stator port  1908  for communication with a mobile phase supply, a second stator port  1910  in communication with a fifth stator port  1912  via an external loop  1914 , a third stator port  1916  for communication with a sample reservoir, a fourth stator port  1918  for sample outflow, and a sixth stator port  1920  for communication with a chromatography column  1922 . In the additional alternative embodiment, the load position  1928  is defined by the first port  1908  and the orifice  1924  communicating with a first channel  1904 , by the second port  1910  and the third port  1916  communicating with the second channel  1906 , and the fourth port  1918  and the fifth port  1912  communicating with the third channel  1926 . In the alternative embodiment, the injection position  2002  is defined by the orifice  1924  and the second port  1910  communicating with the first channel  1904 , and by the fifth port  1912  and the sixth port  1920  communicating with the third channel  1926 , which is connected to a column  1922  connected to the sixth port  1920 . 
     Referring to  FIGS. 22 and 23 , the present disclosure may be used to push an internal sample through a column, wherein the output of the column is provided to other equipment rather than through the valve, incorporating the structure and flow paths of the first embodiment depicted in  FIGS. 3-6  excerpt for the third channel  408 , and the seventh port  316  and the eighth port  318 , which are omitted.  FIG. 22  is an illustration of the relative positions of the face of the stator and the face of the rotor of the additional alternative embodiment of the present invention in the load position.  FIG. 23  is an illustration of the relative positions of the face of the rotor and the face of the rotor of the additional alternative embodiment of the present invention in the injection position. Referring to  FIG. 22 , the valve  710  has a circular stator  2202 , formed integrally with the elongate barrel  726  of a single block of monolithic material to form or provide an integrated barrel-stator  716 , and a circular rotor  2250  where the two components cooperate to permit or preclude fluid communication among various parts of the valve  710 . The stator  2202  has an orifice  2220  at its centerpoint, as well as a first stator port  2204  for communication with a mobile phase supply, a second stator port  2206  in communication with a fifth stator port  2212  via a loop  2260 , a third stator port  2208  for communication with a sample reservoir, a fourth stator port  2210  for outflow of sample waste, and a sixth stator port  2214  for communication with a chromatography column  2280 . The rotor  2250  therefore has a surface adjacent the stator  2202  and two channels, or slots,  2254 ,  2256  in its surface. The rotor  2250  is rotatable with respect to the stator  2202  about the centerpoint between the load position  2222  and the injection position  2232 . The injection position  2232  of the nano-scale operation of the pump section  102 , showing the positions of the stator  2202  and the rotor  2250 , is depicted in  FIG. 23 . The first channel  2254 , the fill/dispense channel, connects the internal pump  708 , via orifice  2220 , to the loop  2260  at port  2212 . The loop  2260  now connects to second channel  2256  containing the sample. Ports  2208  and  2210  are now isolated, preventing further inflow of any sample. Similarly, port  2204  is isolated, preventing further inflow of mobile phase. As second channel  2256  containing the sample now connects to the inlet of the column  2280  via port  2214 , providing a complete flow path so the mobile phase pushes the sample through the column  2280  and to any connected detector. 
     The stroke of the pump section  102 , as illustrated in general in  FIGS. 7 and 8 , is particularly illustrated in  FIGS. 12A and 12B , wherein the stroke  1202  of the pump section  102  is illustrated between the maximum load position  502 ,  1502 ,  1710 ,  1928  and the maximum injection position  602 ,  1602 ,  1802 ,  2002 . The stroke  1202  may be 0.25 inches, or slightly smaller, or 0.75 inches, or slightly larger, or may be between, such as at 0.50 inches. As can be appreciated, the stroke  1202  and the diameter of the barrel  726  determine the volume of fluid transmitted during each load and injection cycle, which, by virtue of their values, are measured in microliters. Operation of the invention and the associated low flow rates are made possible by use of the integration of the pump section  102  and the valve section  104 , unlike conventional products. 
     Referring to  FIGS. 7, 8, 9, 10, 11, 12A and 12B , operation of the integrated nano-scale pump and injection valve  100  is provided by the body  724 , the linear pump actuator  204 , and the integrated barrel-stator  716 . The linear pump actuator  204  includes a plunger-driving piston  712  connected to the plunger  706 . A plunger  706 , at least equal in length to the stroke  1202  and nearly-equivalent to the diameter of the interior chamber  702 , is attached to the end of the plunger-driving piston  712 . In the load position  502 ,  1502 ,  1710 ,  1928 , the plunger  706  is at its maximum retraction within the elongate barrel  726  and defines the maximum volume which may be moved during the stroke  1202 . In the injection position  602 ,  1602 ,  1802 ,  2002 , the plunger  706  is at its maximum displacement into the elongate barrel  726 . The volume displaced during the stroke  1202  between the maximum position associated with the loading  502 ,  1502 ,  1710 ,  1928  and the maximum position associated with the injection  602 ,  1602 ,  1802 ,  2002  is equal to the volume of the plunger  706  introduced into the elongate barrel  726 . The position of the plunger  706  in the barrel  726  and its extent during the stroke be determined with mechanical systems such as optical encoders, or others known in the art, and the maximum extent may be defined and operation limited by mechanical stops or limit switches. 
     Thus, the integral nano-scale pump and injection valve  100  includes a body having a pump section  102  and a valve section  104  where the body has a pump  708  in the pump section  102  and a valve  710  in the valve section  104 . The pump  708  functions linearly by using an elongate barrel  726  and a plunger  706 . As the barrel provides an internal chamber in which the plunger  706  moves, drawing or ejecting fluid from one end while the plunger  706  is moved from the opposing end, the elongate barrel  726  is characterized by an open proximal end, an open distal end, a length, and a sidewall, which define the interior chamber  702 . As detailed, the internal chamber  702  is adapted to receive a supply of mobile phase, and provides operation in connection with the plunger  706  by having an inner diameter sized to the plunger, an outer diameter sized to fit within the pump section and a wall thickness therebetween to provide sufficient strength. The plunger  706 , which has a substantially uniform cross-section, is slidably disposed within the interior chamber  702  and is sized to ensure effective operation during the load position  502 ,  1502 ,  1710 ,  1928  and the injection position  602 ,  1602 ,  1802 ,  2002 . 
     The present invention provides an integral nano-scale pump and injection valve  100  for high performance liquid chromatography which includes an integrated barrel-stator  716 , which has an elongate barrel  726  at a first end and a stator  302 ,  1302 ,  1712 ,  1932  at a second end, a plunger  706  slidably disposed within an interior chamber  702  of the barrel  726  of substantially uniform cross-section, and a rotor  402 , wherein the pump  708  and valve  710  are switchable between a load position  502 ,  1502 ,  1710 ,  1928  and a injection position  602 ,  1602 ,  1802 ,  2002 . The circular rotor  402  has a surface adjacent the stator  302  and has a plurality of channels  404 ,  406 ,  408 ,  1404 ,  1406 ,  1408 ,  1410  in its surface and is rotatable with respect to the stator  302 ,  1302  about a centerpoint between the load position  502 ,  1502 ,  1710 ,  1928  and the injection position  602 ,  1602 ,  1802 ,  2002 . The elongate barrel  726  portion of the integrated barrel-stator  716  includes an open proximal end, an open distal end, a length, and a sidewall defining the interior chamber  702  adapted to receive a supply of fluid and which has an inner diameter, an outer diameter, and a wall thickness. The circular stator  302  has an orifice  320  at its centerpoint and a first side and a second side such that the elongate barrel open distal end is aligned with the second side of the stator  302  at the centerpoint and the interior chamber  702  includes the orifice  320 . The pump  708  is therefore in communication with the valve  710  at the orifice  320 . Because of the integrated nature of the pump  708  and valve  710 , it is desirable that the pressure be measured within the elongate barrel  726 . Unfortunately, the integrated barrel-stator  716  is necessarily monolithic and therefore precludes the presence of a pressure transducer within the elongate barrel  726 , or intermediate the elongate barrel  726  and the associated rotor  402 . While the pressure could be monitored external the valve  710 , such an arrangement would frustrate the operation of the integrated nano-scale pump and injection valve system  100  as it would require a further pressure control system. However, as illustrated in  FIG. 24 , the pressure within the elongate barrel  726  may be measured external the integrated barrel-stator  716  without any orifice or contact with the interior or the integrated barrel-stator  716 . This immediate pressure determination would typically be accomplished by a pressure transducer intermediate the pump and valve, but the integration of those two in the present invention precludes a conventional intermediate component. Therefore the integration of a pressure transducer into the present system is accomplished by determining the effect of pressure of the barrel itself. The integrated barrel-stator  716  may provide an elongate barrel  708  having a thickness  2410  along a first side  2408  of the integrated barrel-stator  716  on the elongate barrel  726  sufficient to sustain the operating pressure of the integrated nano-scale pump  708  and injection valve system  100  but sufficiently thin to deform proportionally to a change in the operating pressure without failing, i.e. leaking or exploding, in a pressure-reading section  2402  and sufficiently elastic to return to its original dimension prior to pressurization so that subsequent readings are consistent with an initial position. This return to original position is essential for proper functioning and measurement of internal pressure. Any combination of material and thickness which fails to return to its original position, i.e. it deforms under pressure, will fail to be usable for the integrated barrel-stator  716 . The thickness  2410  is a property of the material selected and the strength of the material of the integrated barrel-stator  716 , i.e. the extent to which it deforms under pressure. A strain gauge  2404  is affixed to the elongate barrel  726  at this pressure reading section  2402  to provide a signal consistent with the extent of the deformation of the elongate barrel  726  while under pressure, which be converted to a pressure reading, thus providing a pressure sensor  2406 . The extent of deformation is measured in respect to the original position, while not under pressure. The strain gauge  2404  is thus affixed to the integrated barrel-stator  716  at the first side  2408  and adapted to detect deflection consistent with a pressure change within the elongated barrel  726 . 
     It may further be advantageous to permit the pressure at which the fluid in the pump  708  is provided from the integrated nano-scale pump and injection valve system  100  to be altered, such as increased or decreased, to a desired pressure. Additionally, pressure control may be desirable where two or more integrated nano-scale pump and injection valve systems  100  are used in conjunction to provide a flow to a t-connector, where a pressure differential between the two integrated nano-scale pump and injection valve systems  100 , such as incident to a difference in compressibility of the associated mobile phases, may result in retarded or back flow from the first integrated nano-scale pump and injection valve system  100  to the second integrated nano-scale pump and injection valve system  100 . Thus, the fluid within an integrated nano-scale pump and injection valve system  100  may be pressurized between the load position  502 ,  1502 ,  1710 ,  1928  and the injection position  602 ,  1602 ,  1802 ,  2002  by operation of the pump, while monitoring pressure, while the rotor  2504  is in an interim position  2502 , as illustrated in  FIG. 25 . By operation of the pump  708  while the rotor  2504  is in the interim position  2502 , where the fluid contained within the elongate barrel  726  has no means of escape, the pressure within the elongate barrel  726  can be increased to the desired pressure by driving the plunger  706  toward the rotor  2504 , or even decreased by retracting the plunger  706  away from the rotor  402 . This interim position  2502  may be characterized the channel  2516  being associated with a dead or pressurizing position  2510  on the face of the stator  2508  at a location intermediate the first stator port  2512  and the second stator port. In the interim position  2502 , the orifice  2506  is exposed to the surface of the rotor  2504 , which may be at a detent on the surface of the rotor  2504 . Unlike other positions on the rotor  2504 , the interim position  2502  provides no outlet. As a result, the contents of the plunger  706  and of the channel  2516  are pressurized prior to connection with a second stator port  2514 . 
     The pump  708  may be engaged while the rotor  402  is in this interim position  2502 , causing the pressure in the elongate barrel  726  to alter to the desired level. Once the desired pressure has been achieved, the rotor  402  is shifted to the injection position  602 ,  1602 ,  1802 ,  2002 . When desired, the rate of advance of the plunger  706  may then be controlled to maintain the desired pressure, as measured by the pressure sensor  2406 . The rate of advance of the plunger  706  may be varied in response to data from the strain gauge  2404  to maintain the desired pressure. 
     The nano-scale operation of the integrated nano-scale pump and injection valve  100  is made possible by integration of parts may be further augmented by sufficient and operable  360  zero-dead volume micrometer fittings, and by material selection. Diamond-coated surfaces may be utilized where beneficial. The plunger  706  may be constructed of a work hardened super alloy, such as MP35N, a nickel-chromium-molybdenum-cobalt alloy providing ultra-high strength, toughness, ductility and high corrosion resistance—particularly from contact with hydrogen sulfide, chlorine solutions and mineral acids (nitric, hydrochloric, and sulfuric). Moveover, the nano-scale operation of the integrated nano-scale pump and injection valve  100  permits portability, such as being battery-operated, while being light weight, having low mobile phase consumption and generating low waste. Additionally, this system, designed particularly for capillary column use, does not employ a splitter, provides a substantial in operation. The integrated nano-scale pump and injection valve  100  can generate up to 110.32 MPa (16,000 psi) pressure, with a pump volume capacity of 24 μL, and a sample volume as low as 10 nL, or higher, such as 60 nL, can be injected As a result of the structures provided herein, the maximum and minimum dispensing volumetric flow rates of the integrated nano-scale pump and injection valve  100  are 74.2 μL/min and 60 nL/min, respectively. This may further be accomplished by providing the loop  506  of 5.08 cm×75 or 150 μm inner diameter stainless steel tubing to carry the mobile phase to the column during injection (dispensing). 
     The terms and expressions which have been employed in the foregoing specification are used therein as terms of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding equivalents of the features shown and described or portions thereof.