Abstract:
The present invention intends to provide a liquid chromatography system capable of improving analytical accuracy and a sample injector and a cleaning device and a method for cleaning. In order to attain the above intention, a liquid chromatography system equipped with a sample injector is provided with a cleaning device for cleaning a sample injection portion disposed in the sample injector, and thereby many samples whose analysis results are different from one another can be consecutively analyzed with high precision.

Description:
[0001]    This application claims the priority of Japanese Patent application No. 2001-266406 filed on 3 rd  September 2001, which is incorporated herein by reference.  
         BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention relates to a liquid chromatography system and a sample injector and a cleaning device and a method for cleaning, in particular to a liquid chromatography system whose configuration allows improving an accuracy in an analytical process of a sample in a sample injector that injects a sample and a sample injector and a cleaning device and a method for cleaning.  
           [0004]    2. Description of the Related Art  
           [0005]    A liquid chromatography system is widely used as an analytical means for separating and analyzing chemical substances. In particular, a liquid chromatography system that uses a semi-micro column having an inner diameter of 1 to 2 mm has advantages in that it can provide analysis results of high sensitivity, high resolution and high precision. Accordingly, an active development thereof is in progress.  
           [0006]    [0006]FIG. 9 shows an example of an existing liquid chromatography system. The liquid chromatography system shown in the same figure includes a sample injector  1 , a pump  2 A, a controller  3 , a separation column  4  and a detector  5 . According to the configuration shown in FIG. 9, a sample is supplied together with a solvent (mobile phase A) supplied from the pump  2 A from the sample injector  1  into the separation column  4  for performing separation.  
           [0007]    A transferred sample is separated in the separation column  4  followed by introducing into the detector  5  where a predetermined analysis operation is performed on the sample. Thus configured liquid chromatography system includes the controller  3  that is constituted of a computer. The controller  3  drives and controls the sample injector  1  and the pump  2 A.  
           [0008]    A schematic diagram of an existing sample injector  1  is shown in FIG. 10. In the same figure, a switching valve  10  is provided with a liquid reservoir  11  and a syringe  12 , and a syringe actuator  13 . The liquid reservoir  11  stores a sample injected through the switching valve  10  from the syringe  12 . The syringe  12  is constituted controllable by the syringe actuator  13 . When the syringe  12  is actuated, a solution is discharged to the switching valve  10 .  
           [0009]    Subsequently, a switching operation of the switching valve  10  performed under the control of the controller  3  will be explained. The switching valve  10 , under the control of the controller  3 , switches a passage of the sample to a first state (a state where the switching valve  10  is set at (A)) and a second state (a state where the switching valve  10  is set at (B)).  
           [0010]    When the switching valve  10  is in the first state, according to the control of the syringe actuator  13 , the sample is discharged from the syringe  12  and is supplied along a line shown by a solid line in the figure through the switching valve  10  into the liquid reservoir  11 , and stored there. On the other hand, when the switching valve  10  is in the second state, along a line shown by a dotted line in the figure, the mobile phase A is supplied from the pump  2 A through the switching valve  10  into the liquid reservoir  11 . The sample stored in the liquid reservoir  11  is supplied once more through the switching valve  10  into the separation column  4 . Furthermore, from the syringe  12 , the sample remained in the syringe  12  or a tube is discharged into a waste liquid reservoir.  
           [0011]    However, when the sample is supplied with the sample injector  1  as mentioned above, a certain degree of the sample remains stuck to a tube between the syringe  12  and the switching valve  10 , a tube between the separation column  4  and the switching valve  10 , the inside of the switching valve  10  and the liquid reservoir  11 . For instance, when, after a sample is analyzed, a mobile phase is injected, as shown in FIG. 11, as a result of analysis, a peak  1  is detected. However, because of an influence of the sample remained in the sample injector  1 , in the subsequent analyses, even when a blank sample such as distilled water is injected, there appear peaks  2  and  3  that should not appear from the nature of things. Accordingly, there is a problem in that when in a state where the sample sticks to the passage in the liquid chromatography system as mentioned above, the analysis of the subsequent sample is followed, the previous sample causes an influence on the analysis of the subsequent sample, resulting in deteriorating the accuracy in the following analyses.  
           [0012]    The present invention is carried out in view of the aforementioned problems and intends to provide a liquid chromatography system capable of improving the accuracy in the analysis and a sample injector and a cleaning device and a method for cleaning.  
         SUMMARY OF THE INVENTION  
         [0013]    In order to achieve the above intention,  
           [0014]    (1). A liquid chromatography system comprising a sample injector of the present invention includes a cleaning device for cleaning a sample injection portion disposed inside of the sample injector.  
           [0015]    According to the present invention, by disposing the cleaning device inside of the sample injector, a passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analysis of the next samples can be improved. Accordingly, for many samples whose analysis results are different from one another, continuous analyses can be performed with high accuracy.  
           [0016]    (2). In a liquid chromatography system equipped with a sample injector set forth in (1), the cleaning device includes a cleaning liquid supply means for supplying the cleaning liquid, when the sample is not supplied from the sample injection portion, toward the sample injection portion.  
           [0017]    According to the present invention, when the cleaning liquid supply means of the cleaning device supplies the cleaning liquid when the sample is not supplied from the sample injection portion, the passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy of the analyses of the subsequent samples can be improved. As a result, when many samples different in their analysis results are consecutively analyzed, the analysis can be performed with higher accuracy.  
           [0018]    (3). In a liquid chromatography system equipped with a sample injector set forth in (1) and (2), the cleaning device includes a switching device for switching supply and stoppage of the cleaning liquid to the sample injector, the cleaning liquid supply means actuates and controls the switching device, and thereby the supply of the cleaning liquid is controlled.  
           [0019]    According to the present invention, the switching device provided to the cleaning device can control the supply and stoppage of the cleaning liquid to the sample injection portion, resulting in efficient cleaning of the passage in the sample injector.  
           [0020]    (4). In a liquid chromatography system equipped with a sample injector set forth in any one of (1) through (3), the cleaning device is disposed detachably with respect to the sample injector.  
           [0021]    According to the present invention, the cleaning device can be detachably disposed to the sample injector, resulting in an improvement in functionality.  
           [0022]    (5). A sample injector of a liquid chromatography system equipped with a sample injection portion for injecting a sample in the sample injector includes a cleaning device that, when the sample is not supplied from the sample injection portion, under the control due to the cleaning liquid supply means, supplies the cleaning liquid toward the sample injection portion.  
           [0023]    According to the present invention, when the cleaning device, under the control of the cleaning liquid supply means, supplies the cleaning liquid toward the sample injection portion, the passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analyses of the following samples can be improved. As a result, many samples whose analysis results are different from one another can be consecutively analyzed with higher accuracy.  
           [0024]    (6). A cleaning device for cleaning a sample injector provided to a liquid chromatography system is configured so that, when the sample is not supplied from the sample injection portion of the sample injector, under the control due to the cleaning liquid supply means, the cleaning liquid may be supplied toward the sample injection portion.  
           [0025]    According to the present invention, when the cleaning device supplies under the control of the cleaning liquid supply means supplies the cleaning liquid toward the sample injection portion, the passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analyses of the following samples can be improved. As a result, many samples whose analysis results are different from one another can be consecutively analyzed with higher accuracy.  
           [0026]    (7). A method for cleaning a sample injector of a liquid chromatography system includes supplying a sample from the sample injection portion provided to the sample injector; and supplying a cleaning liquid for cleaning the sample injection portion from a cleaning device provided to the sample injector.  
           [0027]    According to the present invention, when the cleaning method includes supplying the sample from the sample injection portion and supplying the cleaning liquid, the sample can be efficiently supplied and the passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analyses of the following samples can be improved. As a result, many samples whose analysis results may be different from one another can be consecutively analyzed with higher accuracy.  
           [0028]    (8). In a method for cleaning set forth in the (7), the supplying the sample includes storing the sample in a liquid reservoir provided to the sample injection portion.  
           [0029]    According to the present invention, when the supplying the sample includes the storing the sample in the liquid reservoir, the stored sample can be efficiently supplied and the passage in the sample injector can be efficiently cleaned. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0030]    [0030]FIG. 1 is a schematic diagram showing a liquid chromatography system according to one embodiment of the present invention.  
         [0031]    [0031]FIG. 2 is a schematic diagram showing a liquid chromatography system according to one embodiment of the present invention.  
         [0032]    [0032]FIG. 3 is a diagram showing a combination (A-A state) of passages of switching valves of the present invention.  
         [0033]    [0033]FIG. 4 is a diagram showing a combination (A-B state) of passages of switching valves of the present invention.  
         [0034]    [0034]FIG. 5 is a diagram showing a combination (B-A state) of passages of switching valves of the present invention.  
         [0035]    [0035]FIG. 6 is a diagram showing a combination (B-B state) of passages of switching valves of the present invention.  
         [0036]    [0036]FIG. 7 is a flowchart showing operations of a sample injector.  
         [0037]    [0037]FIG. 8 is a diagram showing an analysis result of the present invention.  
         [0038]    [0038]FIG. 9 is a diagram showing one example of a conventional liquid chromatography system.  
         [0039]    [0039]FIG. 10 is a schematic diagram of a conventional sample injector.  
         [0040]    [0040]FIG. 11 is a diagram showing a conventional analysis result. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0041]    In the following, embodiments of the present invention will be detailed with reference to the drawings. FIG. 1 is a schematic diagram showing a liquid chromatography system according to one embodiment of the present invention. The liquid chromatography system shown in FIG. 1 is differently constituted in the inside of a sample injector  20  from that of the conventional one. In FIGS. 1 through 8 shown in the following, the same components as those shown in FIGS. 9 and 10 are given the same reference numerals and explanations thereof will be omitted.  
         [0042]    [0042]FIG. 2 is a schematic diagram showing a sample injector according to one embodiment of the present invention. In FIG. 2, the sample injector  20  includes a cleaning device  30 , a sample injection portion  40  and so on. The cleaning device  30  includes a switching valve  31 , a backing pump  32  and so on. Furthermore, the sample injection portion  40  includes a liquid reservoir  11 , a switching valve  10 , a syringe  12 , a syringe actuator  13  and so on. A controller  3  controls the switching valves  31  and  10 , the backing pump  32  and the syringe actuator  13 .  
         [0043]    The switching valves  10  and  31 , respectively, include rotatable valve bodies  10 R and  31 R. The valve bodies  10 R and  31 R are provided with six ports  100  through  105  and  310  through  315 , respectively. The switching valves  10  and  31  are switched between an (A) state and a (B) state due to the control of the controller  3 . In the state (A), in the switching valve  31 , the ports  311  and  312 , ports  313  and  314 , and ports  315  and  310 , respectively, are connected to communication passages  31   a ,  31   b  and  31   c , and in the switching valve  10 , the ports  101  and  102 , ports  103  and  104 , and ports  105  and  100 , respectively, are connected to communication passages  10   a ,  10   b  and  10   c.    
         [0044]    On the other hand, in the state (B), in the switching valve  31 , the ports  310  and  311 , ports  312  and  313 , and ports  314  and  315 , respectively, are connected to communication passages  31   a ,  31   b  and  31   c , and in the switching valve  10 , the ports  100  and  101 , ports  102  and  103 , and ports  104  and  105 , respectively, are connected to communication passages  31   a ,  31   b  and  31   c.    
         [0045]    Furthermore, the port  310  is connected through a detachable valve  35  to the port  100 . The port  311  is connected to the backing pump  32 , and the port  312  is connected to a waste liquid reservoir (not shown in the figure). The port  313  is connected through a detachable valve  36  to the port  105  The port  314  is connected through a detachable valve  34  to the separation column  4 . The port  315  is connected through a detachable valve  33  to the pump  2 A.  
         [0046]    Still furthermore, the port  101  is connected to one end of the liquid reservoir  11  that stores the sample. The other end of the liquid reservoir  11  is connected to the port  104 . The port  102  is connected to the waste liquid reservoir and the port  103  is connected to an outlet of the syringe  12 .  
         [0047]    In the backing pump  32 , a mobile phase C that becomes a cleaning liquid is disposed so that it may be supplied by a pump pressure. The syringe  12 , inside of which the sample is injected, is connected to the syringe actuator  13  that controls the discharge of the sample.  
         [0048]    Subsequently, a switching operation of the switching valves  31  and  10  that is implemented by the control of the controller  3  will be explained. Combinations of the passages obtained when each of the switching valves  31  and  10  is switched into the state (A) or (B) are shown in FIGS. 3 through 6.  
         [0049]    In FIG. 3, a state (A-A state) obtained when the switching valve  31  is switched to (A) and the switching valve  10  is switched to (A) is shown. The mobile phase A supplied from the pump  2 A, after going past the communication passage  31   a  of the switching valve  31 , goes through the communication passage  10   a  of the switching valve  10 , and is supplied through the communication passage  31   c  of the switching valve  31  to the separation column  4 . Furthermore, at this time, the sample supplied from the syringe  12 , after going past the communication passage  10   c , is stored in the liquid reservoir  11 . Furthermore, the mobile phase C from the backing pump  32 , after going through the communication passage  31   b , is discharged into the not shown waste liquid reservoir. Thus, in the (A)-(A) state shown in FIG. 3, the mobile phase A is supplied to each of the passages and a passage for storing the sample in the liquid reservoir  11  is formed.  
         [0050]    In FIG. 4, a state (A-B state) obtained when the switching valve  31  is switched to (A) and the switching valve  10  is switched to (B) is shown. The mobile phase A supplied from the pump  2 A, after going past the communication passage  31   a  of the switching valve  31 , goes through the communication passage  10   a  of the switching valve  10 , and is supplied into the liquid reservoir  11 . Thereafter, the sample stored in the liquid reservoir  11  is discharged and is supplied through the communication passage  10   c  of the switching valve  10  and the communication passage  31   c  of the switching valve  31  to the separation column  4 . Furthermore, the mobile phase C from the backing pump  32 , after going through the communication passage  31   b , is discharged into the not shown waste liquid reservoir. Thus, in the A-B state shown in FIG. 4, a passage for discharging the sample stored in the liquid reservoir  11  is formed.  
         [0051]    In FIG. 5, a state (B-A state) obtained when the switching valve  31  is switched to (B) and the switching valve  10  is switched to (A) is shown. The mobile phase C supplied from the backing pump  32 , after going past the communication passage  31   a  of the switching valve  31 , goes through the communication passage  10   a  of the switching valve  10  and the communication passage  31   b  of the switching valve  31 , and is discharged into the waste liquid reservoir. Thus, in the B-A state shown in FIG. 5, a passage for partially cleaning the passage therethrough the sample is supplied is formed.  
         [0052]    In FIG. 6, a state (B-B state) that is obtained when the switching valve  31  is switched to (B) and the switching valve  10  is switched to (B) is shown. The mobile phase C supplied from the backing pump  32 , after going past the communication passage  31   a  of the switching valve  31  and the communication passage  10   a  of the switching valve  10 , goes through the liquid reservoir  11 , goes through the communication passage  10   c  of the switching valve  10  and the communication passage  31   b  of the switching valve  31 , and is discharged into the waste liquid reservoir. Thus, in the B-B state shown in FIG. 6, a passage for total cleaning of the passage therethrough the sample is supplied is formed.  
         [0053]    In the following, a cleaning process in the sample injector will be explained with reference to FIGS. 1 through 7. FIG. 7 is a flowchart showing a cleaning process that is performed with the controller  3 . When a cleaning program shown in the same figure is implemented, first, in the step S 10 , prior to the start of the cleaning program, whether or not the sample is injected in the syringe  12  is decided. At this time, the switching valves  31  and  10  are in the A-B state (initial state).  
         [0054]    Then, when it is decided “NO” in a step S 10 , that is, when it is judged that there is no sample injected in the syringe  12 , since there is no need of injecting a sample in the liquid reservoir  11  and of cleaning with the cleaning liquid both of which are implemented after a step  11 , without implementing the process after the step S 11 , the cleaning process is over.  
         [0055]    On the contrary, when it is judged “YES” in the step  10 , that is, when it is judged that there is the sample injected in the syringe  12 , the liquid chromatography system starts cleaning in the sample analysis process and in the sample injector  20  both of which are the steps after the step S 11 .  
         [0056]    First, in the step S 11 , under the control of the controller  3 , as shown in FIG. 3, both of the switching valves  31  and  10  are changed to the (A) state, thereby the mobile phase A is sent out of the pump  2 A and the syringe  12  injects the sample into the liquid reservoir  11 . When the sample is stored in the liquid reservoir  11 , a step S 12  is followed.  
         [0057]    In the step S 12 , under the control of the controller  3 , as shown in FIG. 4, the switching valve  31  is changed to the (A) state and the switching valve  10  is changed to the state (B), the mobile phase A is supplied from the pump  2 A to the liquid reservoir  11 , the sample in the liquid reservoir  11  is transferred into the separation column  4 , and thereby the analysis starts.  
         [0058]    In a step S 13 , whether or not the sample has been completely transferred from the liquid reservoir  11  to the separation column  4  is decided. The time during which the sample transfer comes to completion, though depending on the predetermined flow rate and amount of sample injection, is normally within 30 seconds. When the step S 13  judges “NO”, that is, when the transfer of sample has not come to completion, the step S 13  is repeated. When the step S 13  judges “YES”, that is, when the transfer of the sample has come to completion, a step S 14  is followed.  
         [0059]    In the step S 14 , under the control of the controller  3 , as shown in FIG. 6, both of the switching valves  31  and  10  are changed to the state (B). Thereby, an analysis system constituted of the separation column  4  and the detector  5  of a system where the analysis is proceeding and an injection system constituted of the sample injector  20  are separated. Accordingly, without influencing on the analysis system, the following steps S 15  through S 17  can be followed. After the separation in the step S 14 , the step S 15  is followed.  
         [0060]    In the step S 15 , under the control of the controller  3 , as shown in FIG. 5, the switching valve  31  is changed to the (B) state and the switching valve  10  is changed to the (A) state. After putting the syringe  12  in a state where the cleaning liquid is separately collected from a designated place, exhaust and suction operation is carried out under the control of the syringe  12 , thereby the passage of the sample in the portion  40  including the syringe  12  and the liquid reservoir  11  are cleaned.  
         [0061]    In the step S 16 , in the B-A state similar to the step S 15 , a blank sample (distilled water, mobile phase A and so on) is injected into the liquid reservoir  11  with the syringe  12 . At the completion of the injection of the blank sample, a step S 17  is followed.  
         [0062]    In the step S 17 , under the control of the controller  3 , as shown in FIG. 6, both of the switching valves  31  and  10  are switched to the (B) state. Thereby, the analysis system and the injection system are separated, and the passage of the injection system is cleaned with the blank sample stored in the liquid reservoir  11 . On completion of the cleaning of the passage, a step S 18  is followed.  
         [0063]    In the step S 18 , under the control of the controller  3 , as shown in FIG. 5, the switching valve  31  is switched to the (A) state and the switching valve  10  is switched to the (B) state. After thus setting in the initial state, a step S 19  is followed.  
         [0064]    In the step S 19 , whether or not a next sample has been injected into the syringe  12  is decided. When it is judged that the next sample is injected into the syringe  12 , the cleaning process starting from the step S 11  is repeated. On the contrary, when the step S 19  is “YES”, that is, when it is judged that the sample is not injected into the syringe  12 , the cleaning process comes to completion.  
         [0065]    Thus, when the cleaning process is performed in the sample injector  20 , the previous sample remaining in the sample injector  20  can be reduced. Thereby, as shown in FIG. 8, when the injected sample is analyzed, only a peak  1  is detected in the analysis result. That is, a peak due to the sample remaining in the sample injector  20  when the mobile phase is injected can be suppressed from occurring. Accordingly, without causing an adverse effect at the time of the next sample injection, the accuracy of the analysis consecutively performed to a plurality of samples can be improved.  
         [0066]    Furthermore, in the cleaning shown in FIG. 7, the cleaning of the liquid reservoir  11  in the step S 15  and the cleaning due to the blank sample in the steps S 16  and S 17  can be appropriately combined a plurality of times or can be combined alternately.  
         [0067]    Still furthermore, when the analysis is performed for many samples whose analysis time periods and analysis results with the liquid chromatography system are different from one another, the setting can be changed under the arbitrary conditions.  
         [0068]    When the detachable valves  33  through  36  are disposed, as needs arise, the cleaning device  30  of the sample injector  20  can be detachably configured.  
         [0069]    As mentioned above, according to the present invention, by disposing the cleaning device in the sample injector, the passages in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passages can be reduced, the accuracy in the analysis of the next samples can be improved. Accordingly, many samples different in the analysis results can be continuously analyzed with high precision.  
         [0070]    According to the present invention, when the cleaning liquid supply means of the cleaning device supplies the cleaning liquid when the sample is not supplied from the sample injection portion, the passages in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passages can be reduced, the accuracy in the analysis of the next samples can be improved. As a result, many samples whose analysis results are different from one another can be continuously analyzed with high precision.  
         [0071]    According to the present invention, the switching device disposed to the cleaning device can perform the supply and stoppage of the cleaning liquid to the sample injection portion, and thereby the passage in the sample injector can be efficiently cleaned.  
         [0072]    According to the present invention, since the cleaning device is detachable to the sample injector, an improvement in the functionality can be attained.  
         [0073]    Furthermore, according to the present invention, when the cleaning device, under the control of the cleaning liquid supply means, supplies the cleaning liquid to the sample injection portion, the passage in the sample injector can be efficiently cleaned. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analysis of the next samples can be improved. As a result, many samples whose analysis results are different from one another can be continuously analyzed with high precision.  
         [0074]    According to the present invention, the supplying the sample from the sample injection portion and supplying the cleaning liquid allow efficiently supplying the sample and efficiently cleaning the passage in the sample injector. Accordingly, since the sample remaining in the passage can be reduced, the accuracy in the analysis of the next samples can be improved. As a result, many samples whose analysis results are different from one another can be continuously analyzed with high precision.  
         [0075]    Furthermore, according to the present invention, when supplying the sample includes storing the sample in the liquid reservoir, the stored sample can be efficiently supplied and the passage in the sample injector can be efficiently cleaned.