Patent Abstract:
A combined dual pump-injector valve utilizing a single piece of material to house the barrel for each of the two piston-based pumps and to provide the stator of the associated valve, thus eliminating any need for connections between the pumps and the valve, and therefore eliminating the potential for high-pressure leaks or pressure reductions. The combined dual pump-injector valve permits injection of nanoliter-sized samples into a chromatographic column such that complete analyses can be completed with microliters of mobile phase with nanoliters of a sample.

Full Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of Ser. No. 14/156,197 entitled “Pump and injector for liquid chromatography” filed on Jan. 15, 2014 and 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 dual pump/injection valve for injection of a nanoliter-sized sample into a chromatography column utilizing a single piece of material to house the barrel for each of the two piston-based pumps and to provide the stator of the associated valve, thus eliminating any need for connections between the pumps 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 system 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 system for high performance liquid chromatography which includes an integrated barrel-stator providing within its integral body a first elongate barrel and a second elongate barrel, and providing on the end of its integral body a stator, such that all three integrally formed of a single piece of material. As can be appreciated the integrated barrel-stator has an integrated barrel-stator first section and an integrated stator barrel second section. The stator has a stator first side, while the first elongate barrel has a first elongate barrel first open end in the integrated stator barrel first section and a second open end at the integrated barrel-stator second section, and a sidewall defining a first interior chamber to receive a supply of fluid at second open end. The first elongate barrel second open end is provided at the stator first side and provides a second stator orifice. Similarly, the second elongate barrel has a second elongate barrel first open end in the integrated stator barrel first section and a second elongate barrel second open end at the integrated barrel-stator second section, and a second elongate barrel sidewall defining an second interior chamber to receive a supply of fluid at first open end, where the second elongate barrel second open end at the stator first side provides a first stator orifice. The stator has a first stator fluid supply port for communication with a liquid supply and has a second stator fluid supply port for communication with a liquid supply, a third stator port, and a fourth stator port. The stator is in contact at a surface of a stator face with a surface of a rotor face of a rotor, and communicates with the rotor at the first stator fluid supply port and at the second stator fluid supply port. The first stator orifice and the second stator orifice are non-overlapping to ensure separateness of operation. A first longitudinal plunger is slidably disposed within the first interior chamber and is of a substantially uniform cross section. A second longitudinal plunger is slidably disposed within the second interior chamber and likewise is of a substantially uniform cross section. 
     In the first embodiment, the rotor has a first channel and a second channel in the rotor face and is rotable with respect to the stator about a centerpoint of the stator between a load position and an injection position. The load position is characterized by the second stator orifice in communication with the first stator fluid supply port via the first channel and the first stator orifice in communication with the second stator fluid supply port via the second channel, such that fluid may be drawn though each port from an external fluid supply. During operation in the load position, the associated pumps are filling due to retraction of the each associated plunger. The injection position characterized by the second stator orifice in communication with the third stator port via the first channel and the first stator orifice in communication with the fourth stator port via the second channel. During operation in the injection position, the associated pumps are imparting fluid due to forward movement of the each associated plunger. 
     As can be appreciated, the chromatographic device may be a chromatographic column. 
     The first embodiment may be modified, to provide a first alternative embodiment, which provides a gradient system with an external sample output to a chromatographic column without a detector. The first alternative embodiment includes, in addition to the elements of the first alternative embodiment, the stator having a fifth stator port, a sixth stator port, a seventh stator port, an eighth stator port, a ninth stator port and a tenth stator port, and a rotor having a third rotor slot in the rotor face, a fourth rotor slot in the rotor face and a fifth rotor slot in the rotor face. In the first alternative embodiment, the load position is further defined by the third stator port and the fourth stator port in communication via an external connector with the fifth stator port, the sixth stator port in communication with the seventh stator port via the third rotor slot, the seventh stator port in communication with a sample loop return, the eighth stator port in communication with a fluid sample source and in communication with the ninth stator port via the fourth rotor slot, the ninth stator port in communication with the sixth stator port via an external sample loop and the tenth stator port in communication with an input to a chromatographic device and in communication with the fifth rotor slot. In the first alternative embodiment, the injection position is further characterized by the third stator port and the fourth stator port being for communication via the external connector with the fifth stator port, the fifth stator port in communication with the sixth stator port via the third rotor slot, the sixth stator port in communication with the ninth stator port via the external sample loop, the ninth stator port in communication with the tenth stator port via the fifth rotor slot, the eighth stator port adapted for communication with the fluid sample source and in communication with the seventh stator port via the fourth rotor slot, the seventh stator port adapted for communication with a sample loop return, and the tenth stator port adapted for communication with the input to the chromatographic device. 
     As can be appreciated, the embodiment need not include the external connectors, columns and detectors, but must be adapted for use with them. 
     The first alternative embodiment may be modified to provide a second alternative embodiment, which provides a gradient system with an external sample with a detector by providing output to a chromatographic column, and provides the output from the chromatographic column to a chromatographic detector. In this second alternative embodiment, the stator further has an eleventh stator port, a twelfth stator port, and a thirteen stator port, while the rotor further has a sixth rotor slot. In the second alternative embodiment, the load position further comprises the eleventh stator port in communication with an input of a chromatographic detector, and the twelfth stator port set to receive the output of the chromatographic column. This is enabled by the twelfth stator port being in communication with the thirteenth stator port via the sixth rotor slot. The injection position thus further comprises the twelfth stator port being adapted to receive the output of the chromatographic column, the twelfth stator port in communication with the eleventh stator port via the sixth rotor slot, and the eleventh stator port being adapted to communicate to an input of a chromatographic detector. 
     In a third alternative embodiment, the first embodiment may be modified to provide a gradient system with an internal sample without a detector by providing a stator which further includes a fifth stator port, a sixth stator port, a seventh stator port, and an eighth stator port, and by providing a stator which further includes a third rotor slot in the rotor face of the rotor. In this fourth alternative embodiment, the load position further includes the third stator port and the fourth stator port being in communication via an external connector with the sixth stator port, the fifth stator port being in communication with an input to a chromatographic device, and the eighth stator port being in communication with a fluid sample source, and in communication with the seventh stator port via the third rotor slot. The injection position therefore further comprises the third stator port and the fourth stator port in communication via an external connector with the sixth stator port, the sixth stator port in communication with the fifth stator port via the third rotor slot, and the fifth stator port adapted for communication with an input to a chromatographic device. The third rotor slot thus contains the entire sample for processing. 
     The third alternative embodiment may be modified, to provide a fourth alternative embodiment, which provides a gradient system with an internal sample with output to a chromatographic column, as the chromatographic device, and provides the output from the chromatographic column to a chromatographic detector. a gradient system with an internal sample with. In this fourth alternative embodiment, the stator further has a ninth stator port and a tenth stator port, and the rotor further has a fourth rotor slot in the rotor face. In this fourth alternative embodiment, the load position further includes the tenth stator port connected to receive an output of the chromatographic column, the ninth stator port in communication with an input of a chromatographic detector. The injection position therefore further includes the tenth stator port set to receive an output of the chromatographic column, the tenth stator port communicating with the ninth stator port via the fourth rotor slot, and the ninth stator port in communication with an input of a chromatographic detector. 
     A fifth alternative embodiment is also provided which permits continuous flow. Like the other embodiments, the integral nano-scale pump and injection valve system for high performance liquid chromatography includes an integrated barrel-stator, said integrated barrel-stator having a first elongate barrel, a second elongate barrel, and a stator integrally formed of a single piece of material. The integrated barrel-stator has an integrated barrel-stator first section and an integrated stator barrel second section, and a stator first side in the integrally formed stator. The first elongate barrel has a first elongate barrel first open end in the integrated stator barrel first section and a second open end at the integrated barrel-stator second section, and a sidewall defining a first interior chamber adapted to receive a supply of fluid at second open end. A first elongate barrel second open end is provided at the stator first side and provides a second stator orifice. The second elongate barrel has a second elongate barrel first open end in the integrated stator barrel first section and a second elongate barrel second open end at the integrated barrel-stator second section, and a second elongate barrel sidewall defining a second interior chamber adapted to receive a supply of fluid at first open end. A second elongate barrel second open end is provided at the stator first side and provides a first stator orifice. The stator has a first stator fluid supply port and a second stator fluid supply port for communication with a liquid supply, as well as a third stator port and a fourth stator port. The stator is in contact at a surface of a stator face with a surface of a rotor face of a rotor and is adapted to communicate with the rotor at the first stator fluid supply port and the second stator fluid supply port. For effective operation, the first stator orifice and the second stator orifice are non-overlapping. A first longitudinal plunger, of substantially uniform cross section, is slidably disposed within the first interior chamber. A second longitudinal plunger, also of substantially uniform cross section, is slidably disposed within the second interior chamber. The rotor has a first channel in the rotor face and a second channel in the rotor face and is rotable with respect to the stator about a centerpoint of the stator among a first position, a second position, and a third position. In the first position, the second pump is loading, i.e. retraction of the plunger away from the rotor, while the first pump is dispensing, i.e. forward movement of the plunger in the associated barrel toward the rotor. As a result, the first position is defined by the second stator orifice communicating with the third stator port-and-slot via the first rotor slot, the third stator port-and-slot communicating with an output, the first stator orifice communicating with the second stator port via the second rotor slot, and the third stator port communicating with a supply. In the second position, both pumps are dispensing. As a result, the second position is defined by the second stator orifice communicating with the third stator port-and-slot via the first rotor slot, the third stator port-and-slot communicating with an output, the first stator orifice communicating with the fourth stator port-and-slot via the second rotor slot, and the fourth stator port-and-slot communicating with an output. In the third position, the first pump is loading while the second pump finishes dispensing. As a result, the third position is defined by the second stator orifice communicating with the third stator port-and-slot via the first rotor slot, the first stator port-and-slot adapted communicating with a supply, the first stator orifice communicating with the fourth stator port-and-slot via the second rotor slot, and the fourth stator port-and-slot communicating with an output. 
     Each embodiment may include a seal within the integral nano-scale pump and injection valve system utilizing a first hard plastic seal, a flexible seal, a second hard plastic seal, all to fit about the plunger, and a driving disk and a spring, provided to interact with a threaded male sleeve, i.e. a sleeve with external threads, of the system. The first hard plastic seal is sized to fit within the first elongate barrel and about, and without contacting, the first longitudinal plunger. The flexible seal is sized to fit within a first elongate barrel and to fit about the first longitudinal plunger, and to contact the longitudinal plunger, adjacent the first hard plastic seal. 
     The second hard plastic seal is sized to fit within the first elongate barrel and about, and without contacting, the first longitudinal plunger, and adjacent the flexible seal. The driving disk includes a bore therethrough sized to fit about the first longitudinal plunger without interference, a first end and a second end, and is sized to freely fit within the integrated barrel-stator adjacent first elongate barrel. The driving disk further includes a shoulder near the first end, and a neck at the second end, the neck sized to fit within the first elongate barrel and to contact the first hard plastic seal. The threaded male sleeve, i.e. the sleeve with external threads, has a bore therethrough sized to permit movement of the first longitudinal plunger without interference, and is sized to a threaded female section, i.e. a sleeve with internal threads, within the integrated barrel-stator adjacent the first elongate barrel. The spring contacts the shoulder of the driving disk and an end of the threaded male sleeve, i.e. the sleeve with external threads, to drive the components towards the seal. 
     Each embodiment may further include a first pump actuator associated with a plunger-driving piston attached to the first longitudinal plunger, as well as a second pump actuator associated with a plunger-driving piston attached to said second longitudinal plunger. Moreover, each embodiment may include a valve actuator associated with a driveshaft attached to the rotor. 
     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 front view of one embodiment of the present invention as assembled and showing the internal components of the pumps. 
         FIG. 2  is a cross-section illustration of the embodiment of  FIG. 1  along line Z-Z, a side view, for the maximum position of one pump in the load position. 
         FIG. 3  is a cross-section illustration of the embodiment of  FIG. 1  along line Z-Z, the side view of  FIG. 2 , for the maximum position of one pump in the injection position. 
         FIG. 4  is an illustration of a close-up, from  FIG. 3  at section C, about the end of the plunger in the barrel illustrating the seal needed for operation at high pressure. 
         FIG. 5  is an illustration of the face of the stator of the first alternative embodiment of the present disclosure. 
         FIG. 6  is an illustration of the face of the rotor of the first alternative embodiment of the present disclosure. 
         FIG. 7  is an illustration of the relative positions of the face of the stator and the face of the rotor of the first alternative embodiment of the present disclosure in the load position. 
         FIG. 8  is an illustration of the relative positions of the face of the stator and the face of the rotor of the first alternative embodiment of the present disclosure in the injection position. 
         FIG. 9  is an illustration of the face of the stator of the second alternative embodiment of the present disclosure. 
         FIG. 10  is an illustration of the face of the rotor of the second alternative embodiment of the present disclosure. 
         FIG. 11  is an illustration of the relative positions of the face of the stator and the face of the rotor of the second alternative embodiment of the present disclosure in the load position. 
         FIG. 12  is an illustration of the relative positions of the face of the stator and the face of the rotor of the second alternative embodiment of the present disclosure in the injection position. 
         FIG. 13  is an illustration of the face of the stator of the third alternative embodiment of the present disclosure. 
         FIG. 14  is an illustration of the face of the rotor of the third alternative embodiment of the present disclosure. 
         FIG. 15  is an illustration of the relative positions of the face of the stator and the face of the rotor of the third alternative embodiment of the present disclosure in the load position. 
         FIG. 16  is an illustration of the relative positions of the face of the stator and the face of the rotor of the third alternative embodiment of the present disclosure in the injection position. 
         FIG. 17  is an illustration of the face of the stator of the fourth alternative embodiment of the present disclosure. 
         FIG. 18  is an illustration of the face of the rotor of the fourth alternative embodiment of the present disclosure. 
         FIG. 19  is an illustration of the relative positions of the face of the stator and the face of the rotor of the fourth alternative embodiment of the present disclosure in the load position. 
         FIG. 20  is an illustration of the relative positions of the face of the stator and the face of the rotor of the fourth alternative embodiment of the present disclosure in the injection position. 
         FIG. 21  is an illustration of the face of the stator of the fifth alternative embodiment of the present disclosure. 
         FIG. 22  is an illustration of the face of the rotor of the fifth alternative embodiment of the present disclosure. 
         FIG. 23  is an illustration of the relative positions of the face of the stator and the face of the rotor of the fifth alternative embodiment of the present disclosure in the first position. 
         FIG. 24  is an illustration of the relative positions of the face of the stator and the face of the rotor of the fifth alternative embodiment of the present disclosure in the second position. 
         FIG. 25  is an illustration of the relative positions of the face of the stator and the face of the rotor of the fifth alternative embodiment of the present disclosure in the third position. 
         FIG. 26  is an illustration of the volume per unit time during operation dispensed by each of the two pumps of the present disclosure and the associated position, of the three positions, for the fifth alternative embodiment. 
         FIG. 27  is an illustration of a close-up about the ends of each of the plungers in their respective barrels in the third position of the fifth alternative embodiment. 
         FIG. 28  is an illustration of the face of the stator of the first embodiment of the present disclosure. 
         FIG. 29  is an illustration of the face of the rotor of the first embodiment of the present disclosure. 
         FIG. 30  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 disclosure in the load position. 
         FIG. 31  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 disclosure in the injection position. 
         FIG. 32  is an illustration of a connector and internal assembly of the present disclosure functioning as a static mixer. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Referring to  FIG. 1 , an embodiment of the integrated nano-scale pump and injection valve system  100  is provided.  FIG. 1  provides an illustration of a front view of one embodiment of the present invention as assembled and showing the internal components of the pumps. As illustrated in  FIG. 1 , the integrated nano-scale pump and injection valve system  100  includes an integrated barrel-stator  110  which provides the interface between the first pump section  102 , the second pump section  112 , and valve section  104 . Each pump section  102 ,  112  includes an actuator  108 ,  114 , the integrated barrel-stator  110  and an external body  130 ,  132  to provide a structural relationship among each pump actuator  108 ,  114 , the pump  118 ,  120 , and the integrated barrel-stator  110 . The valve section  104  includes an actuator  106 . 
     Unlike the prior art where a valve and pump were separate bodies simply joined together, in the integrated nano-scale pump and injection valve system  100 , as illustrated in  FIGS. 1-4 , the elongate barrel  116  of the first pump  118 , the elongate barrel  122  of the second pump  120  and the stator  210  of the valve  124  are integrally formed of a single piece to provide direct communication between the first pump  118  and the valve  124  and between the second pump  120  and the valve  124  without introducing any fittings or connectors which may swell or leak during high pressure operation. Referring to  FIGS. 1-4, 27 , by forming the elongate barrel  116  of the first pump  118  and the second pump  120  and the stator  210  of the valve  124  of a single part as integrated barrel-stator  110 , the integrated nano-scale pumps and injection valve system  100  may operate at high pressures without degradation incident to intervening parts and fittings. 
     Notably, the present invention provides a pump-and-injection system not only capable of pumping small volumes, and at high pressures, but also capable of providing a gradient system application, which permits substantially faster operation that conventional applications. For the first embodiment and all but the fifth alternative embodiment, the first position provides a load position where a sample flows through a groove or loop and where both the first and second pump are filling, i.e. the plunger is retracted and thus moved away from the rotor. Notably, the two pumps need not have the same carrier (mobile phase). For the second embodiment and all but the fifth alternative embodiment, the second position provides an inject position, where both pumps aspirate simultaneously, i.e. where the plunger is driven toward the rotor, one or the other, with the same, or different velocities, wherein the flow of the pumps may gradually grow or decline, depending on desirable mix volumes. The combined flow from the two pumps therefore mixes, such as in a tee, before entering a chromatographic column. After the injection cycle finishes, the system is switched again to the first, or load position. Because each pump, and the valve, has its actuator, each may be independently controlled. Additionally, as provided in the fifth alternative embodiment, the system may be uses to provide continuous flow where the two pumps have the same liquid. 
     A cross-section illustration of the present invention along line Z-Z of  FIG. 1  for the maximum position of the first pump  118  in the load position  202 , i.e. the plunger  206  is at the maximum retraction from the rotor  214 , is provided in  FIG. 2 . A cross-section illustration of the present invention along line Z-Z of  FIG. 1  for the maximum position of the first pump  118  in the injection position  302 , i.e. the plunger  206  is at the maximum position when driven toward the rotor  214 , is provided in  FIG. 3 . Operation of the second pump  120  is consistent with the operation of the first pump  118 . 
     Referring to  FIG. 2 , in the load position  202 , the pump plunger  206  of the first pump  118  is being retracted for filling the interior chamber  208 . 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 first pump  118  thus includes a pump plunger  206 , an interior chamber  208  defined by an elongate barrel  116 , and the plunger  206 . The second pump  120  is identically constructed to include a pump plunger, an interior chamber defined by the elongate barrel, and a plunger. Referring to  FIG. 2 , the arrangement and nano-scale operation of integrated nano-scale pump and injection valve system  100  is illustrated in at the maximum position of the first pump  118  in the load position  202 . 
     Upon initiation of loading, the first pump  118  is positioned in the load position  202  and the plunger  206  is retracted by the piston  212  and draws a solvent from a reservoir, such as through a 15 cm×200 μm steel tube into the barrel  116 . At the same time and independent of pump filling, a sample is introduced into the sample loop through a capillary, which is connected to the port  308  on the pump and to a sample supply, preferably using a zero-dead volume connector. This capillary may be sized to 5.08 cm×75 μm inner diameter. The second pump  120  is loaded in the same manner, potentially, but not necessarily, at the same time. 
     After completion of loading, the integrated nano-scale pump and injection valve system  100  may be switched for injection, changing the direction of operation of the first pump  118 , and potentially, but not necessarily, the second pump  120 , and changing the position of the valve  124 . Referring to  FIG. 3 , in the injection position  302 , the pump plunger  206  of the first pump  118  is being driven forward to empty the interior chamber  208 . During injection, the plunger  206  of the first pump  118  is driven by the piston  212  into the barrel  116 . The rate of advance, and therefore the dispensing flow rate, may be controlled by power supply and/or by computer software. 
     By switching between the maximum extent of the load position  202  and the maximum extent of the injection position  302 , each pump  118 ,  120  of the integrated nano-scale pump and injection valve system  100  may be sized to hold microliters for use with nano-scale columns for quick separation. Due to the volumes involved, refilling of each pump  118 ,  120 , of the integrated nano-scale pump and injection valve system  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 system  100 . Moreover, with the use of two pumps  118 ,  120 , separation may be continued beyond the volume of one pump by concurrent or consecutive pump operations. 
     The stroke  218  of each pump  118 ,  120 , is illustrated in  FIGS. 2 and 3 , and defined by the difference in position of the pump plunger  206  between the maximum load position  202  and the maximum injection position  302 . The stroke  218  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  218  and the diameter of the barrel  116  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 sections  102 ,  112  and the valve section  104 , unlike conventional products. 
     Referring to  FIG. 4 , a close-up about the end of the plunger  206  in the barrel  116  for operation at high pressure, such as above 10000 psi, it is essential that a strong seal  404  be positioned about the plunger  206  within the barrel  116  of the integrated barrel-stator  110 , at least a stroke-length  218  above or beyond the first end  140  of the plunger  206  when in the maximum injection position so as to contact the plunger  206  and to form a seal thereabout. Positioning the seal  404  less than a stroke-length  218  from the first end  140  of the plunger  206  would cause the seal  404  to fail when the plunger  206  was fully retracted to reach the maximum load position. While a single seal across the barrel  116 , through which the plunger  206  would move, may be used, a composite seal is preferable. As depicted in  FIG. 4 , the seal  404  about the plunger  206  within the barrel  116  may be formed of a compressed sequence of a first hard seal  406 , which does not contact the plunger  206 , a flexible seal  408 , which contacts the plunger  206 , and a second hard seal  410 , which does not contact the plunger  206 , placed under compression by a driving disk  412  maintained within the integrated barrel-stator  110 . The diameter of the barrel  116  of the integrated barrel-stator  110  is enlarged for that section more than a stroke-length  218  above or beyond the first end  140  of the plunger  206  when in the maximum injection position to accept a first hard plastic seal  406 . The first hard plastic seal  406  may be composed of a material such as polyether ether ketone (PEEK) or another material, and is sized to fit within the barrel  116  and about the plunger  206  without precluding movement of the plunger  206 . Atop the first hard plastic seal  406  is positioned a flexible seal  408 . The flexible seal  408  is composed of a compressible sealing material, such as polytetrafluoroethylene (PTFE). The flexible seal  408  is sized to fit within the barrel  116  and about the plunger  206  without precluding movement of the plunger  206 . Atop the flexible seal  408  is positioned a second hard plastic seal  410 , 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  116  and about the plunger  206  without precluding movement of the plunger  206 . Compression of the flexible seal  408  results in lateral expansion of the flexible seal  408  and thereby causes the flexible seal  408  to provide a seal against the plunger  206  which does not preclude movement of the plunger  206 , between the first hard seal  406  and the second hard seal  410 . This may be accomplished by application of force against the second hard seal  410  and a shoulder  414  in the barrel  116  to maintain the position of the first hard seal  406 . The application of force against the second hard seal  410  may be obtained by joining a sleeve with external threads, a threaded male sleeve or nut,  416 , having a bore therethrough to freely accommodate the plunger  206  and piston  212  without interference, to the integrated barrel-stator  110 , above or beyond the seal  404 , which sleeve with external threads  416  would apply force to one or more springs  418 , particularly a Belleville spring also known as a coned disc spring, positioned within the integrated barrel-stator  110  above or adjacent the barrel  116 , to force a driving disk  412  to compress the second hard seal  412 . The sleeve with external threads  416  is sized to a sleeve with internal threads, i.e. a threaded female section,  432  of the integrated barrel-stator  110  above or adjacent the barrel  116 . The driving disk  412  includes a bore  420  sized to permit the plunger  206  to pass therethrough without interference, a shoulder  422  to permit the application of force against the driving disk  412  from the springs  418  smaller in diameter than the sleeve with external threads  416  so as not to contact the inner walls of the integrated barrel-stator  110 , and a neck  424  at its end  426  proximate the barrel  116  sized to enter the barrel  116  without interference and having sufficient height to contact and apply force against the second hard seal  410 . As a result, the neck  424  is driven against the second hard seal  410 , which is in turn driven into the flexible seal  408  to compress it and form a seal about the plunger  206 . The plunger  206  is therefore able to move through the flexible seal  408  without fluid seeping past, even as the flexible seal  408  may become pliable during repeated movement of the plunger  206 . Because only the flexible seal  408  laterally contacts the plunger  206 , and because the balance of the components, including the integrated barrel-stator  110 , the sleeve with external threads  416 , and the driving disk  412 , include sufficient clearance for the plunger  206  to move without interference, the plunger  206  can move within the barrel  116  and can operate to draw or eject fluid into the barrel  116  and through the stator  210 , particularly at high pressure. 
     Thus, the seal  404  includes a first hard plastic seal  406 , a flexible seal  408 , and a second hard plastic seal  410  and is compressed to cause the flexible seal  408  to seal about the plunger  206  by a driving disk  412 , a sleeve with external threads  416 , and one or more springs  418 . The first hard plastic seal  406  is sized to fit within the barrel  116  and to fit about the plunger  206 , without contacting the plunger  206 . The flexible seal  408  is sized to fit within the barrel  116  and to fit about the plunger  206  adjacent the first hard plastic seal  406 . The second hard plastic seal  410  is sized to fit within the barrel  116  and to fit about the plunger  206 , without contacting the plunger  206 , and adjacent the flexible seal  408 . The driving disk  412  has a bore  420  therethrough sized to fit about the plunger  206  without interference, a first end  428  and a second end  426 . The driving disk  412  is sized to freely fit within said integrated barrel-stator  110  adjacent the barrel  116 , and includes a shoulder  422  near the first end  428 , and a neck  424  at the second end  426 , which neck  424  is sized to fit within the barrel  116  and to contact the first hard plastic seal  406 . The sleeve with external threads  416  has a bore therethrough sized to permit movement of the plunger  206  without interference and is sized to a threaded female section within the integrated barrel-stator  110  above, or adjacent, the barrel  116 . The spring  418  contacts the shoulder  422  of the driving disk  412  and an end of the sleeve with external threads  416  and is compressed as the sleeve with external threads  416  is driven into the integrated barrel-stator  110 . 
     Referring to  FIGS. 1, 2, 3, and 4 , operation of each pump  118 ,  112  of the integrated nano-scale pump and injection valve system  100  is provided by the linear pump actuator  108 , and the integrated barrel-stator  110 . The linear pump actuator  108  includes a plunger-driving piston  212  connected to the plunger  206 . A plunger  206 , at least equal in length to the stroke  218  and nearly-equivalent to the diameter of the interior chamber  208 , is attached to the end of the plunger-driving piston  212 . In the load position  202 , the plunger  206  is at its maximum retraction within the elongate barrel  116  and defines the maximum volume which may be moved during the stroke  218 . In the injection position  302 , the plunger  206  is at its maximum displacement into the elongate barrel  116 . The volume displaced during the stroke  218  between the maximum position associated with the loading  202  and the maximum position associated with the injection  302  is equal to the volume of the plunger  206  introduced into the elongate barrel  116 . The position of the plunger  206  in the barrel  116  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 system  100  includes a body having a first pump section  102 , a second pump section  112 , and a valve section  104  where the body has a first pump  118  in the first pump section  102 , a second pump  120  in the second pump section  112  and a valve  124  in the valve section  104 . Each pump  118 ,  120  functions linearly by using an elongate barrel  116  and a plunger  206 . As the barrel provides an internal chamber in which the plunger  206  moves, drawing or ejecting fluid from one end while the plunger  206  is moved from the opposing end, the elongate barrel  116  is characterized by an open proximal end, an open distal end, a length, and a sidewall, which define the interior chamber  208 , interior to the integrated barrel-stator  110 . As detailed, the interior chamber  208  is adapted to receive a supply of mobile phase, or other liquid, and provides operation in connection with the plunger  206  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  206 , which has a substantially uniform cross-section, is slidably disposed within the interior chamber  208  and is sized to ensure effective operation during the load position  202  and the injection position  302 . 
     Referring to  FIG. 27 , to permit operation of the first pump  118  and the second pump  120  with a common integrated barrel-stator  110 , rather than providing a single pump along the centerline  2702  of the integrated barrel-stator  110 , the first pump  118  and the second pump  120  are mounted equivalently near the centerline  2702  of the integrated barrel-stator  110  opposite the face, i.e. the outer surface, of the stator  210  so that the elongate pump barrel  116  of the first pump  118  and the elongate pump barrel  116 B of the second pump  120  are angled toward to the centerline  2702 , to intersect the centerline  2702  just beyond the face of the stator  210 , thus providing a first stator orifice  2704  and a second stator orifice  2706  on the face of the stator  210 . Alternatively, the first pump  118  and the second pump  120  need not be mounted equivalently near the centerline  2702  of the integrated barrel-stator  110  opposite the face of the stator  210 —so long as the end of the elongate pump barrel  116  provides a first stator orifice  2704  on the face of the stator  210  and the end of the second elongate pump barrel  116 B provides a second stator orifice  2706  on the face of the stator  210 , such that the first stator orifice  2704  and the second stator orifice  2706  are positioned to permit operation, most likely symmetrically about the centerline  2702 . 
     As a plunger  206  of a pump  118 ,  120  is driven forward by the piston  212 , the content of the barrel is driven forward along a flow path provided by the valve  124 , which result from the construction of the face of the stator  210  and the face, i.e. the outer surface, of the rotor  214 . 
     Referring to  FIGS. 28, 29, 30 and 31 , in a first embodiment, the integral nano-scale pump and injection valve system  100  may be used to provide a gradient system. The valve  124  has a circular stator  210 , formed integrally with the elongate barrel  116  to form integrated barrel-stator  110 , and a circular rotor  214  where the stator  210  and the rotor  214  cooperate to permit or preclude fluid communication among various parts of the valve  124  depending on whether the valve  124  is in the load position  202  or the injection position  302 . The stator  210  for this first embodiment is illustrated in  FIG. 28 , while the rotor  214  is illustrated in  FIG. 29 . 
     Referring to  FIG. 28 , the stator  210  of the first embodiment has on its stator face  2802  a first stator orifice  2812  and a second stator orifice  2814  equally positioned about at its centerpoint  2702 , together with a first stator port  2806 , a second stator port  2810 , a third stator port  2804 , and a fourth stator port  2808 . Referring to  FIG. 29 , the rotor  214  of the first embodiment has on its rotor face  2902  a first rotor slot  2904 , and a second rotor slot  2906 , forming channels, in its surface. The first rotor slot  2904  and the second rotor slot  2906  are generated with an overlapping three lobe structure such that one of two large lobes of each rotor slot each fully communicates with a first stator orifice  2812  or a second stator orifice  2814  depending on the position of the stator  210  and the rotor  214 , while the third lobe provides communication to the other stator ports  2102 ,  2108  and ports-and-slots  2104 ,  2106 . 
     The rotor  214  is rotatable with respect to the stator  210  about the centerpoint  2702  between the load position  202  and the injection position  302 . In the load position  202  the mobile phase, or other liquid, is delivered to the interior chamber  208  of the first pump  118  and the second pump  120 . 
     In the load position  202  of the first embodiment, depicted in  FIG. 30 , the stator face  2802  includes a first stator port  2806  for communication by the first pump  118  with a first mobile phase, or other liquid, supply via a first rotor slot  2904 , and a second stator port  2810  for communication by the second pump  120  with a second mobile phase, or other liquid, supply via the second rotor slot  2906 . In this load position  202 , both the first pump  118  and the second pump  120  are loading, and thus suctioning fluid from the second stator orifice  2814  and the first stator orifice  2812 , respectively, where the first stator orifice  2812  is in communication with the second stator port  2810  via the second rotor slot  2906  and the second stator orifice  2814  is in communication with the first stator port  2806  via the first rotor slot  2904 . 
     Referring to  FIG. 31 , in the injection position  302  of the first embodiment, the rotor  214  is rotated in the valve  124  by the drive shaft  216 , which may be at or about 20 degrees or which may be at another selected angle, so that the existing stator ports and the existing rotor slots to create a second set of flow paths. The second stator orifice  2814  is in communication with the third stator port  2804  via the first rotor slot  2904 , providing outflow, i.e. dispensing, from the first pump  118 . The first stator orifice  2812  is in communication with the fourth stator port  2808  via the second rotor slot  2906 , providing outflow, i.e. dispensing, from the second pump  120 . The third stator port  2804  and the fourth stator port  2808  thus provide outflow, i.e. dispensing, from the first pump  118  and the second pump  120 . The first stator port  2806  and the second stator port  2810 , each in communication with the carrier supply, are each now isolated. 
     First Alternative Embodiment 
     Referring to  FIGS. 5, 6, 7 and 8 , in a first alternative embodiment, the integral nano-scale pump and injection valve system  100  may be used to provide a gradient system, using an external sample to be provided to a chromatographic column  704 , but not necessarily to a chromatographic detector. The valve  124  has a circular stator  210 , formed integrally with the elongate barrel  116  to form integrated barrel-stator  110 , and a circular rotor  214  where the stator  210  and the rotor  214  cooperate to permit or preclude fluid communication among various parts of the valve  124  depending on whether the valve  124  is in the load position  202  or the injection position  302 . The stator  210  for this first alternative embodiment is illustrated in  FIG. 5 , while the rotor  214  is illustrated in  FIG. 6 . 
     Referring to  FIG. 5 , the stator  210  of the first alternative embodiment has on its stator face  502  a second stator orifice  526  and a first stator orifice  524  equally positioned about at its centerpoint  2702 , together with a first stator port  506 , a second stator port  522 , a third stator port  504 , a fourth stator port  520 , a fifth stator port  508 , a sixth stator port  510 , a seventh stator port  512 , an eighth stator port  514 , a ninth stator port  516 , a tenth stator port  518 . Referring to  FIG. 6 , the rotor  214  of the first alternative embodiment has on its rotor face  602  a first rotor slot  604 , a second rotor slot  612 , a third rotor slot  606 , a fourth rotor slot  608 , and a fifth rotor slot  610 , forming channels, in its surface. While the third rotor slot  606 , the fourth rotor slot  608  and the fifth rotor slot  610  are arcs of nearly elliptical shape positioned distant the centerpoint  2702 , the first rotor slot  604  and the second rotor slot  612  are generated with an overlapping three lobe structure such that one of two large lobes of each rotor slot each fully communicates with a second stator orifice  526  or a first stator orifice  524  depending on the position of the stator  210  and the rotor  214 , while the third lobe provides communication to the other stator orifices  504 ,  506 ,  508 ,  510 ,  512 ,  514 ,  516 ,  518 ,  520 ,  522 ,  524 . 
     The rotor  214  is rotatable with respect to the stator  210  about the centerpoint between the load position  202  and the injection position  302 . In the load position  202 , components are isolated while the mobile phase, or other liquid, is delivered to the interior chamber  208  of the first pump  118  and the second pump  120 . 
     In the load position  202  of the first alternative embodiment, depicted in  FIG. 7 , the stator face  502  includes a third stator port  504  in communication via a first external connector  706   a  with a three-way connector  708 , and a fourth stator port  520  in communication via a second external connector  706   b  with a three-way connector  708  which is in communication with the fifth stator port  508  via a third external connector  706   c . This provides a line on standby. The three-way connector  708  and/or the third external connector  706   c  function as a static mixer to ensure the two inputs are thoroughly and completely mixed so as to provide a homogeneous solution. With respect to the three-way connector  708 , static mixing of the low flow rates of the present disclosure may be accomplished by the three-way connector  708  being a mixing tee. With respect to use of the third external connector  706   c  as a static mixer, as illustrated in  FIG. 32 , an internal member  3202  is inserted within the third external connector  706   c  to create turbulence within the third external connector  706 . The internal member  3202  may comprise a plate  3204  twisted along its longitudinal axis  3206 . 
     The stator face  502  further includes a first stator port  506  for communication by the first pump  118  with a first mobile phase, or other liquid, supply via a first rotor slot  604 , and a second stator port  522  for communication by the second pump  120  with a second mobile phase, or other liquid, supply via the second rotor slot  612 . The stator face  502  includes a sixth stator port  510  in communication with the seventh stator port  512  via the third rotor slot  606 , from which an outflow of a sample loop  702  exits from the seventh stator port  512 , and in communication with outflow from the ninth stator port  516 . The eighth stator port  514  is in communication with the external sample flow and in communication with the ninth stator port  516  via the fourth rotor slot  608 . A sample loop  702  is thus created between the ninth stator port  516  and the sixth stator port  510 . The tenth stator port  518  is in communication with an external chromatographic column  704  and in communication with the fifth rotor slot  610  and provides a line on standby. In this load position  202 , both the first pump  118  and the second pump  120  are loading, and thus suctioning fluid from the first stator orifice  524  and the second stator orifice  526 , respectively, where the first stator orifice is in communication with the second stator port  522  via the second rotor slot  612  and the second stator orifice is in communication with the first stator port  506  via the first rotor slot  604 . 
     Referring to  FIG. 8 , in the injection position  302  of the first alternative embodiment, the rotor  214  is rotated in the valve  124  by the drive shaft  216 , which may be at or about 20 degrees, so that the existing stator ports and the existing rotor slots to create a second set of flow paths. The second stator orifice  526  is in communication with the third stator port  504  via the first rotor slot  604 , providing outflow, i.e. dispensing, from the first pump  118 . The first stator orifice  524  is in communication with the fourth stator port  520  via the second rotor slot  612 , providing outflow, i.e. dispensing, from the second pump  120 . The third stator port  504  and the fourth stator port  520  thus provide outflow, i.e. dispensing, from the first pump  118  and the second pump  120  and are operably in communication with the three-way connector  708  prior to communication with the fifth stator port  508 . The first stator port  506  and the second stator port  522 , each in communication with the carrier supply, are each now isolated. Because the fifth stator port  508  is also in communication with the sixth stator port  510  via the third rotor slot  606 , the sample contained in the sample loop  702 , including that portion of the sample contained in the third rotor slot  606  is driven through the sample loop  702  by communication with the sixth stator port  510 , which is also in communication with the ninth stator port  516 . The tenth stator port  518  is in communication with the fourth stator port  520  via the fifth rotor slot  610 , which then provides the moving sample to a chromatographic column  704 , or other device. The sample supply continues to provide flow, through the ninth stator port  516  which is in communication with the eighth stator port  514  via the fourth rotor slot  608 , as the eighth stator port  514  is adapted for communication with, and during operation is in communication with, the sample supply and the ninth stator port  516  provides outflow. 
     The column  704  may therefore maintained at pressure and isolated while the interior chambers  208  of the first pump  118 , as illustrated in  FIG. 2 , and the second pump  120  is filled by a mobile phase, or other liquid. For initial charging of the column  704 , the operator can run the mobile phase, or other liquid, through the eighth stator port  514 , through the sample loop  702 , and out the seventh stator port  512 , switching between the load position  202  and the injection position  302  to fill the column  704  and to ensure no bubbles are present in the system. 
     The external sample loop  702 , which carries the mobile phase, or other liquid, to the column during injection (dispensing), may have a small inner diameter, such as 75 or 150 μm, may be of materials selected by the operator, such as stainless steel or fused silica. and may be of a length sized to each pump  118 ,  120 , such as a length of 5.08 cm. 
     Second Alternative Embodiment 
     Referring to  FIGS. 9, 10, 11 and 12 , in a second alternative embodiment, the integral nano-scale pump and injection valve system  100  may be used to provide a gradient system, using an external sample to be provided to a chromatographic column  1104  and thereafter to a chromatographic detector  1106 . 
     The stator  210  for the second alternative embodiment is illustrated in  FIG. 9 , while the rotor  214  is illustrated in  FIG. 10 . The arrangement of the first pump  118  and the second pump  120  remains consistent with the first alternative embodiment. The second alternative embodiment departs from the first alternative embodiment by the use of an eleventh stator port  928 , a twelfth stator port  930 , and a thirteen stator port  932 , which in connection with a sixth rotor slot  1014  permits a return from the column  1104  to be controlled and directed to a chromatographic detector  1106 . 
     Referring to  FIG. 9 , the stator  210  of the second alternative embodiment has on its stator face  902 , a first stator orifice  924  and a second stator orifice  926  equally positioned about at its centerpoint  2702 , together with a third stator port  904 , a first stator port  906 , a fifth stator port  908 , a sixth stator port  910 , a seventh stator port  912 , an eighth stator port  914 , a ninth stator port  916 , a tenth stator port  918 , a fourth stator port  920 , a second stator port  522 , an eleventh stator port  528 , a twelfth stator port  530 , and a thirteenth stator port  532 . Referring to  FIG. 10 , the rotor  214  of the second alternative embodiment has on its rotor face  1002  a first rotor slot  1004 , a second rotor slot  1012 , a third rotor slot  1006 , a fourth rotor slot  1008 , a fifth rotor slot  1010 , and a sixth slot  1014 , forming channels, in its surface. While the third rotor slot  1006 , the fourth rotor slot  1008  and the fifth rotor slot  1010  are arcs of nearly elliptical shape positioned distant the centerpoint  2702 , the first rotor slot  1004  and the second rotor slot  1012  are generated with an overlapping three lobe structure such that one of two large lobes of each rotor slot each fully communicates with a first stator orifice  924  or a second stator orifice  926  depending on the position of the stator  210  and the rotor  214 , while the third lobe provides communication to the other stator orifices  904 ,  906 ,  908 ,  910 ,  912 ,  914 ,  916 ,  918 ,  920 ,  922 ,  924 . 
     In the load position  202  of the second alternative embodiment, depicted in  FIG. 11 , the stator face  902  includes a third stator port  904  in communication via a first external connector  1110   a  with a three-way connector  1108  and a fourth stator port  920  in communication via a second external connector  1110   b  with a three-way connector  1108 , which is in turn in communication with the fifth stator port  908  via a third external connector  1110   c . This provides a line on standby. The three-way connector  1108  and/or the third external connector  1110   c  function as a static mixer to to ensure the two inputs are thoroughly and completely mixed so as to provide a homogeneous solution as previously described in connection with the first alternative embodiment. The stator face  902  further includes a first stator port  906  for communication by the first pump  118  with a first mobile phase, or other liquid, supply via a first rotor slot  1004 , and a tenth stator port  1022  for communication by the second pump  120  with a second mobile phase, or other liquid, supply via the second rotor slot  1012 . The stator face  902  includes a sixth stator port  910  in communication with the seventh stator port  912  via the third rotor slot  1006 , from which an outflow of a sample loop exits from the seventh stator port  912 , and in communication with outflow from the ninth stator port  916 . The eighth stator port  914  is in communication with the external sample flow and in communication with the ninth stator port  916  via the fourth rotor slot  1008 . A sample loop  1102  is thus created between the ninth stator port  916  and the sixth stator port  910 . The tenth stator port  918  is adapted for communication with, and during operation is in communication with, the input of the external chromatographic column  1104  and in communication with fifth rotor slot  1010 . The output of the external chromatographic column  1104  is in communication with the twelfth stator port  930 , which is in communication with the thirteenth stator port  932  via the sixth rotor slot  1014 , and which provides a line on standby. The eleventh stator port  928  is isolated, except to communication with the input to a chromatographic detector  1106 . In this load position  202 , both the first pump  118  and the second pump  120  are loading, and thus suctioning fluid from the second stator orifice  926  and the first stator orifice  924 , respectively, where the first stator orifice is in communication with the second stator port  922  via the second rotor slot  1012  and the second stator orifice  926  is in communication with the first stator port  906  via the first rotor slot  1004 . 
     Referring to  FIG. 12 , in the injection position  302  of the second alternative embodiment, the rotor  214  is rotated in the valve  124  by the drive shaft  216 , which may be at or about 20 degrees, so that the existing stator ports and the existing rotor slots to create a second set of flow paths. The second stator orifice  926  is in communication with the third stator port  904  via the first rotor slot  1004 , providing outflow, i.e. dispensing, from the first pump  118 . The first stator orifice  924  is in communication with the fourth stator port  920  via the second rotor slot  1012 , providing outflow, i.e. dispensing, from the second pump  120 . The third stator port  904  and the fourth stator port  920  thus provide outflow, i.e. dispensing, from the first pump  118  and the second pump  120  and are operably in communication, with the three-way connector  1108 , prior to communication with the fifth stator port  908 . The first stator port  906  and the second stator port  922 , each in communication with the carrier supply, are each now isolated. Because the fifth stator port  908  is also in communication with the sixth stator port  910  via the third rotor slot  1006 , the sample contained in the sample loop  1102 , including that portion of the sample contained in the third rotor slot  1006  is driven through the sample loop  1102  by communication with the sixth stator port  910 , which is also in communication with the ninth stator port  916 . The tenth stator port  918  is in communication with the fourth stator port  920  via the fifth rotor slot  1010 , which then provides the moving sample to a chromatographic column  1104 , whereafter the separated sample is returned to the valve  124  at the twelfth stator port  930 , which communicates with eleventh stator port  928  via the sixth rotor slot  1014  to provide the separated sample to the chromatographic detector  1106 . While in the injection position, the first stator port  906 , the second stator port  922 , and the thirteenth stator port  932  are isolated from other stator ports. The sample supply continues to provide flow, through the ninth stator port  916  which is in communication with the eighth stator port  914  via the fourth rotor slot  1008 , as the eighth stator port  914  is adapted for communication with, and during operation is in communication with, the sample supply and the ninth stator port  916  provides outflow. As both ends of the column  1104  can be connected to the integrated nano-scale pump and injection valve system  100  to maintain pressure during filling of the integrated nano-scale pump and injection valve system  100  when the flow through the column  1104  is stopped, if desired. This would eliminate a delay period for column re-pressurization. 
     Third Alternative Embodiment 
     Referring to  FIGS. 13, 14, 15 and 16 , in a third alternative embodiment, the integral nano-scale pump and injection valve system  100  may be used to provide a gradient system, providing a sample in an internal sample groove  1502  to a chromatographic column  1504 , but not thereafter to a chromatographic detector. 
     The stator for the third alternative embodiment is illustrated in  FIG. 13 , while the rotor is illustrated in  FIG. 14 . The arrangement of the first pump  118  and the second pump  120  remains consistent with the first alternative embodiment. The third alternative embodiment departs from the first and second alternative embodiments by the reducing the number of stator ports and rotor slots, and provides only an internal sample, rather than the potentially larger external sample. 
     Referring to  FIG. 13 , the stator  210  of the third alternative embodiment has on its stator face  1302  a first stator orifice  1320  and a second stator orifice  1322  equally positioned about at its centerpoint  2702 , together with a first stator port  1306 , a second stator port  1318 , a third stator port  1304 , a fourth stator port  1316 , a fifth stator port  1308 , a sixth stator port  1310 , a seventh stator port  1312 , and an eighth stator port  1314 . Referring to  FIG. 14 , the rotor  214  of the second alternative embodiment has on its rotor face  1402  a first rotor slot  1404 , a third rotor slot  1006 , and a fourth rotor slot  1008 , forming channels, in its surface. While the third rotor slot  1006  is an arc of nearly elliptical shape positioned distant the centerpoint  2702 , the first rotor slot  1404  and the second rotor slot  1412  are generated with an overlapping three lobe structure such that one of two large lobes of each rotor slot each fully communicates with a first stator orifice  1320  or a second stator orifice  1322  depending on the position of the stator  210  and the rotor  214 , while the third lobe provides communication to the other stator orifices  1304 ,  1306 ,  1308 ,  1310 ,  1312 ,  1314 ,  1316 ,  1318 . 
     In the load position  202  of the third alternative embodiment, depicted in  FIG. 15 , the stator face  1302  includes a third stator port  1304  in communication via a first external connector  1506   a  with a three-way connector  1508  and a fourth stator port  1316  in communication via a second external connector  1506   b  with a three-way connector  1108 , which is in communication with the sixth stator port  1310  via a third external connector  1110   c . This provides a line on standby. The three-way connector  1508  and/or the third external connector  1506   c  function as a static mixer to to ensure the two inputs are thoroughly and completely mixed so as to provide a homogeneous solution as previously described in connection with the first alternative embodiment. The stator face  1302  further includes a first stator port  1306  for communication by the first pump  118  with a first mobile phase supply via a first rotor slot  1404 , and a second stator port  1318  for communication by the second pump  120  with a second mobile phase, or other liquid, supply via the second rotor slot  1408 . The stator face  1302  includes a fifth stator port  1308  in communication with an external chromatographic column  1504 , also on standby. The eighth stator port  1314  is adapted for communication with, and during operation is in communication with, the external sample flow and in communication with the seventh stator port  1312  via the third rotor slot  1406 . A sample groove  1502  is thus created between eighth stator port  1314  and the seventh stator port  1312 . In this load position  202 , both the first pump  118  and the second pump  120  are loading, and thus suctioning fluid from the second stator orifice  1322  and the first stator orifice  1320 , respectively, where the first stator orifice  1320  is in communication with the second stator port  1318  via the second rotor slot  1408  and the second stator orifice  1322  is in communication with the first stator port  1306  via the first rotor slot  1404 . 
     Referring to  FIG. 16 , in the injection position  302  of the third alternative embodiment, the rotor  214  is rotated in the valve  124  by the drive shaft  216 , which may be at or about 45 degrees, so that the existing stator ports and the existing rotor slots to create a second set of flow paths. The second stator orifice  1322  is in communication with the third stator port  1304  via the first rotor slot  144 , providing outflow, i.e. dispensing, from the first pump  118 . The first stator orifice  1320  is in communication with the fourth stator port  1316  via the second rotor slot  1408 , providing outflow, i.e. dispensing, from the second pump  120 . The third stator port  1304  and the fourth stator port  1316  thus provide outflow, i.e. dispensing, from the first pump  118  and the second pump  120  and are operably in communication with the three-way connector  1508 , prior to communication with the sixth stator port  1310 . The first stator port  1306  and the second stator port  1318 , each in communication with the carrier supply, are each now isolated. Because the sample contained in the sample groove  1502  is rotated to be in communication with the sixth stator port  1310 , into which the outflow, i.e. dispensing, from the first pump  118  and the second pump  120  is provided, and the fifth stator port  1308  is adapted for communication with, and during operation is in communication with, the input to the chromatographic column  1504 , the sample contained in the sample groove  1502  is provided to the column  1504  while the valve  124  is in the injection position  302 . While in the injection position, the first stator port  1306 , the seventh stator port  1312 , the eighth stator port  1314 , and the second stator port  1318  are isolated from other stator ports. 
     Fourth Alternative Embodiment 
     Referring to  FIGS. 17, 18, 19 and 20 , in a third alternative embodiment, the integral nano-scale pump and injection valve system  100  may be used to provide a gradient system, providing a sample in an internal sample groove  1902  to a chromatographic column  1904  and then to a chromatographic detector  1906 . 
     The stator  210  for the fourth alternative embodiment is illustrated in  FIG. 17 , while the rotor  1810  is illustrated in  FIG. 18 . The arrangement of the first pump  118  and the second pump  120  remains consistent with the third alternative embodiment. The fourth alternative embodiment departs from the third alternative embodiment by the use of a ninth stator port  1724 , a tenth stator port  1726 , which in connection with a fourth rotor slot  1810  in the rotor face  802  permits a return from the column  1904  to be controlled and directed to a chromatographic detector  1906 . 
     In the load position  202  of the fourth alternative embodiment, depicted in  FIG. 19 , the stator face  1702  includes a third stator port  1704  in communication via a first external connector  1910   a  with a three-way connector  1908  and a fourth stator port  1716  in communication via a second external connector  1910   b  with a three-way connector  1908  which in communication with the sixth stator port  1710  via a third external connector  1910   c . This provides a line on standby. The three-way connector  1908  and/or the third external connector  1910   c  function as a static mixer to to ensure the two inputs are thoroughly and completely mixed so as to provide a homogeneous solution as previously described in connection with the first alternative embodiment. The stator face  1702  further includes a first stator port  1706  for communication by the first pump  118  with a first mobile phase, or other liquid, supply via a first rotor slot  1804 , and a second stator port  1718  for communication by the second pump  120  with a second mobile phase, or other liquid, supply via the second rotor slot  1808 . The stator face  1702  includes a fifth stator port  1708  which is adapted for communication with, and during operation is in communication with, the input to an external chromatographic column  1904 , also on standby. The tenth stator port  1726  is adapted for communication with, and during operation is in communication with, the output of the chromatographic column  1904 . The ninth stator port  1724  is adapted for communication with, and during operation is in communication with, the input of the chromatographic detector  1906 . The eighth stator port  1714  is adapted for communication with, and during operation is in communication with, the external sample flow and in communication with the seventh stator port  1712  via the third rotor slot  1806 . A sample groove  1902  is thus created between eighth stator port  1714  and the seventh stator port  1712 . In this load position  202 , both the first pump  118  and the second pump  120  are loading, and thus suctioning fluid from the second stator orifice  1722  and the first stator orifice  1720 , respectively, where the first stator orifice  1720  is in communication with the second stator port  1718  via the second rotor slot  1808  and the second stator orifice  1722  is in communication with the first stator port  1706  via the first rotor slot  1804 . 
     Referring to  FIG. 20 , in the injection position  302  of the fourth alternative embodiment, the rotor  214  is rotated in the valve  124  by the drive shaft  216 , which may be at or about 45 degrees, so that the existing stator ports and the existing rotor slots to create a second set of flow paths. The second stator orifice  1722  is in communication with the third stator port  1704  via the first rotor slot  144 , providing outflow, i.e. dispensing, from the first pump  118 . The first stator orifice  1720  is in communication with the fourth stator port  1716  via the second rotor slot  1808 , providing outflow, i.e. dispensing, from the second pump  120 . The third stator port  1704  and the fourth stator port  1716  thus provide outflow, i.e. dispensing from the first pump  118  and the second pump  120  and are operably in communication, with the three-way connector  1908 , prior to communication with the sixth stator port  1710 . Each of the first stator port  1706  and the second stator port  1718 , adapted for communication with, and during operation in communication with, the carrier supply, are now isolated. Because the sample contained in the sample groove  1902  is rotated to be in communication with the sixth stator port  1710 , into which the outflow, i.e. dispensing from the first pump  118  and the second pump  120  is provided, and the fifth stator port  1708  is adapted for communication with, and during operation is in communication with, the input to the chromatographic column  1904 , the sample contained in the sample groove  1902  is provided to the column  1904  while the valve  124  is in the injection position  302 . The output from the chromatographic column, from which the separated sample is provided, is in communication with the tenth stator port  1726 , which communicates with the ninth stator port  1724  via the fourth rotor slot  1810 . As the ninth stator port  1724  is adapted for communication with, and during operation is in communication with, the input to a chromatographic detector  1906 , the separated sample is provided to the chromatographic detector  1906 . While in the injection position, the first stator port  1706 , the seventh stator port  1712 , the eighth stator port  1714 , and the second stator port  1718  are isolated from other stator ports. 
     Fifth Alternative Embodiment 
     Referring to  FIGS. 21-26 , the integral nano-scale pump and injection valve system  100  may be used to provide a pump without regard to the equipment connected thereto, which provided continuous flow, without the intermittent pressure and flow interruption caused by a binary switch between two pumps. Operation is accomplished by two pumps which may both provide dispersal at the same time, at the same or different flow rates, thus avoiding the even momentary interruption of pressure and flow rate present in convention switching systems by the use of aggregate flow rates from the combination of the two pumps, as controlled by an external controller. 
     The stator  210  for the fifth alternative embodiment is illustrated in  FIG. 21 , while the rotor  214  is illustrated in  FIG. 22 . The arrangement of the first pump  118  and the second pump  120  remains consistent with the third alternative embodiment. The fifth alternative embodiment departs from the prior embodiments by providing a pump for continuous operation, which may be used in connection with other chromatographic equipment. Continuous operation is made possible by incorporating alternating operation of the first pump  118  and the second pump  120 , rather the concurrent operation of the prior embodiments, and by utilizing a first position, a second position, and a third position, rather than load and injection positions. 
     Referring to  FIG. 21 , the stator  210  of the fifth alternative embodiment has on its stator face  2114 , a first stator orifice  2110  and a second stator orifice  2112 , equally positioned about at its centerpoint  2702 , together with a first stator port  2102 , a second stator port  2108 , a third stator port-and-slot  2104 , and a fourth stator port-and-slot  2106 . Referring to  FIG. 22 , the rotor  214  of the fifth alternative embodiment has on its rotor face  2202  a first rotor slot  2204 , and a second rotor slot  2206 , forming channels, in its surface. The first rotor slot  2204  and the second rotor slot  2206  are generated with an overlapping three lobe structure such that one of two large lobes of each rotor slot each fully communicates with a first stator orifice  2110  or a second stator orifice  2112  depending on the position of the stator  210  and the rotor  214 , while the third lobe provides communication to the other stator ports  2102 ,  2108  and ports-and-slots  2104 ,  2106 . 
     In the first position  2306 , illustrated in  FIG. 23 , the first pump  118  is in injection mode, dispensing the carrier, while the second pump  120  is in load mode, suctioning the carrier. The first pump  118  is in communication with the second stator orifice  2112 , which is communication with the third stator port-and-slot  2104  via the first rotor slot  2204 . The third stator port-and-slot  2104  is adapted for communication with, and during operation is in communication with, a three-way connector output  2304 , which may also be a static mixer, and provides an output thereto by dispensing. The second pump  120  is in communication with the first stator orifice  2110 , which is in communication with the second stator port  2108  via the second rotor slot  2206 . The third stator port  2108  is adapted for communication with, and during operation is in communication with, a common supply via a three-way connector  2302 , and obtains the supply thereto to be drawn in to the second pump  120  under suction. 
     In the second position  2406 , illustrated in  FIG. 24 , which follows the first position  2306 , the first pump.  118  is still in injection mode, dispensing the carrier, while the second pump  120  also now in injection mode, albeit behind the first pump  118  in time. The first pump  118  is in communication with the second stator orifice  2112 , which is communication with the third stator port-and-slot  2104  via the first rotor slot  2204 . The third stator port-and-slot  2104  is adapted for communication with, and during operation is in communication with, a three-way connector output  2304 , which may also be a static mixer, and provides an output thereto by dispensing. The second pump  120  is in communication with the first stator orifice  2110 , which is in communication with the fourth stator port-and-slot  2106  via the second rotor slot  2206 . The fourth stator port-and-slot  2106  is adapted for communication with, and during operation is in communication with, the three-way connector output  2304  and provides an output thereto by dispensing. 
     In the third position  2506 , illustrated in  FIG. 25 , the first pump  118  is in load mode, while the second pump  120  is in injection mode dispensing the carrier. The first pump  118  is in communication with the second stator orifice  2112 , which is communication with the third stator port-and-slot  2102  via the first rotor slot  2204 . The first stator port-and-slot  2102  is adapted for communication with, and during operation is in communication with, a common supply via a three-way connector  2302  and obtains the supply thereto to be drawn in to the first pump  118  under suction. The second pump  120  is in communication with the first stator orifice  2110 , which is in communication with the fourth stator port-and-slot  2106  via the second rotor slot  2206 . The fourth stator port-and-slot  2106  is adapted for communication with, and during operation is in communication with, a three-way connector output  2304 , which may also be a static mixer. The simultaneous injection by the second pump  120  and the loading by the first pump  118  are illustrated in  FIG. 27 , an illustration of a close-up about the ends of each of the plungers in their respective barrels in the third position. 
     As illustrated in  FIG. 26 , as the first pump  118  and the second pump  120  are set to cycle so that one is always in injection mode, the volume per unit time injected from the integral nano-scale pump and injection valve system  100  is constant, such that as the volume injected from of one pump reduces over time, the volume injected from the other pump likewise increases, providing a constant volume per unit time. This is accomplished by sequencing through the adjacent position during operation until the desired volume has been dispersed, i.e. first position  2306 , second position  2406 , third position  2506 , second position  2406 , first position  2306 , second position  2406 , third position  2506 , etc. 
     Thus, the present invention provides an integral nano-scale pump and injection valve system  100  for high performance liquid chromatography which includes an integrated barrel-stator  110 , which has an elongate barrel  116  in an integrated barrel-stator first section  220  and a stator  210  at an integrated barrel-stator second section  222 , a plunger  206  slidably disposed within an interior chamber  208  of the barrel  116  of substantially uniform cross-section, and a rotor  214 , wherein the first pump  118  and second pump  120  and valve  124  are switchable between a load position  202  and an injection position  302 . The circular rotor  214  has a surface adjacent the stator  210  and has a plurality of channels or slots in its surface and is rotatable with respect to the stator  210  about a centerpoint between the load position  202  and the injection position  302 . The elongate barrel  116  portion of the integrated barrel-stator  110  includes an open proximal end, an open distal end, a length, and a sidewall defining the interior chamber  208  adapted to receive a supply of fluid and which has an inner diameter, an outer diameter, and a wall thickness. The circular stator  210  has two orifices positioned about 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  210  at the centerpoint and the interior chamber  208  includes the orifice  320 . The first pump  118  is therefore in communication with the valve  124  at the orifice  320 . 
     The nano-scale operation of the integrated nano-scale pump and injection valve system  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  206  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). Moreover, the nano-scale operation of the integrated nano-scale pump and injection valve system  100  permits portability, such as being battery-operated, while being light weight, having low mobile phase, or other liquid, 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 system  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 system  100  are 74.2 μL/min and 60 nL/min, respectively. This may further be accomplished by providing the sample loop  702 ,  1102  of tubing to carry the mobile phase, or other liquid, to the column during injection (dispensing). The sample loop may have a small inner diameter, such as 75 or 150 μm, may be of materials selected by the operator, such as stainless steel or fused silica. and may be of a length sized to each pump  118 ,  120 , such as a length of 5.08 cm. 
     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.

Technology Classification (CPC): 5