Unit for non-continuous sample fractionation and integration, and dual online multifunctional liquid chromatography device having same

Abstract

Disclosed are non-continuous sample fractionating and concatenating device and a dual online multidimensional liquid chromatography system having the same. The non-continuous sample fractionating and concatenating device according to an embodiment of the present disclosure includes a sample supply module which supplies a sample to be analyzed, and a sample fractionation module connected to the sample supply module, and which is continuously supplied with the sample, sets a plurality of unit sample supply times obtained by equally dividing a total sample supply time during which the sample is supplied from the sample supply module, sets a plurality of unit fractionation intervals obtained by equally dividing each of the plurality of unit sample supply times, and concatenates and stores the sample supplied during corresponding unit fractionation intervals within each unit sample supply time to acquire a plurality of fractions.

1 . A non-continuous sample fractionating and concatenating device, comprising:
 a sample supply module which supplies a sample to be analyzed; and   a sample fractionation module connected to the sample supply module, and which is continuously supplied with the sample, sets a plurality of unit sample supply times obtained by equally dividing a total sample supply time during which the sample is supplied from the sample supply module, sets a plurality of unit fractionation intervals obtained by equally dividing each of the plurality of unit sample supply times, and concatenates and stores the sample supplied during corresponding unit fractionation intervals within each unit sample supply time to acquire a plurality of fractions.   
     
     
         2 . The non-continuous sample fractionating and concatenating device according to  claim 1 , wherein the sample fractionation module includes:
 a first fractionation valve connected to the sample supply module, into which the sample is introduced;   a second fractionation valve provided adjacent to the first fractionation valve; and   a plurality of fraction storage loops provided corresponding to a number of the plurality of unit fractionation intervals within the unit sample supply time, each having one end connected to the first fractionation valve and the other end connected to the second fractionation valve, to concatenate and store the sample supplied during the corresponding unit fractionation intervals within each of the unit sample supply times in a sequential order.   
     
     
         3 . The non-continuous sample fractionating and concatenating device according to  claim 2 , wherein the first fractionation valve includes:
 a fraction inlet port through which the sample is introduced from the sample supply module;   a plurality of first fraction storage loop connection ports provided adjacent to the fraction inlet port, each connected to one end of the plurality of fraction storage loops; and   a first connecting channel connecting the fraction inlet port and one of the plurality of first fraction storage loop connection ports in communication with each other corresponding to the unit fractionation interval, and   the second fractionation valve includes:   a plurality of second fraction storage loop connection ports to which the other end of the plurality of fraction storage loops is each connected;   a fraction outlet port provided adjacent to the plurality of second fraction storage loop connection ports, and connected to the other end of one of the plurality of fraction storage loops to discharge the fraction; and   a second connecting channel connecting the fraction outlet port and one of the plurality of second fraction storage loop connection ports in communication with each other corresponding to the unit fractionation interval.   
     
     
         4 . The non-continuous sample fractionating and concatenating device according to  claim 3 , wherein the sample supply module includes:
 a first sample supply valve to which a first pump and a sample injector are connected, wherein the first pump supplies a first solvent; and   a second sample supply valve connected to the first sample supply valve to receive the sample supplied from the first sample supply valve and supply the sample to the fraction inlet port.   
     
     
         5 . The non-continuous sample fractionating and concatenating device according to  claim 4 , wherein the first sample supply valve includes:
 a first sample inlet port connected to the sample injector;   a first sample outlet port provided adjacent to the first sample inlet port;   a first solvent inlet port connected to the first pump;   a first solvent outlet port provided adjacent to the first solvent inlet port and connected to the second sample supply valve; and   a first sample storage loop connection port and a second sample storage loop connection port to which two ends of a sample storage loop are each connected,   in a state that the first sample storage loop connection port and the second sample storage loop connection port are each connected to the first sample inlet port and the first sample outlet port, the sample is stored in the sample storage loop, and   in a state that the first sample storage loop connection port and the second sample storage loop connection port are each connected to the first solvent inlet port and the first solvent outlet port, the first solvent is injected into the sample storage loop to supply the sample to the second sample supply valve.   
     
     
         6 . The non-continuous sample fractionating and concatenating device according to  claim 5 , wherein the second sample supply valve includes:
 a second sample inlet port connected to the first solvent outlet port;   a second sample outlet port provided adjacent to the second sample inlet port and connected to the fraction inlet port; and   a sample separation column having two ends, each connected to the second sample inlet port and the second sample outlet port, so that the sample is eluted at the second sample outlet port, and   the sample eluted in the sample separation column is supplied to the fraction inlet port.   
     
     
         7 . A dual online multidimensional liquid chromatography system, comprising:
 a non-continuous sample fractionating and concatenating device which is continuously supplied with a sample to be analyzed, sets a plurality of unit sample supply times obtained by equally dividing a total sample supply time during which the sample is supplied, sets a plurality of unit fractionation intervals obtained by equally dividing each of the plurality of unit sample supply times, and supplies a plurality of fractions acquired by concatenating and storing the sample supplied during corresponding unit fractionation intervals within each unit sample supply time;   a dual column valve to which a first reversed-phase liquid chromatography column and a second reversed-phase liquid chromatography column are connected, and having a first solid phase extraction column connected to the first reversed-phase liquid chromatography column and a second solid phase extraction column connected to the second reversed-phase liquid chromatography column; and   a column selection module provided between the non-continuous sample fractionating and concatenating device and the dual column valve to supply the fractions supplied from the non-continuous sample fractionating and concatenating device in a sequential order to the first solid phase extraction column and the first reversed-phase liquid chromatography column or the second solid phase extraction column and the second reversed-phase liquid chromatography column in alternating manner.   
     
     
         8 . The dual online multidimensional liquid chromatography system according to  claim 7 , wherein the non-continuous sample fractionating and concatenating device includes:
 a sample supply module which supplies the sample; and   a sample fractionation module connected to the sample supply module to continuously receive the sample supplied from the sample supply module to acquire a plurality of fractions and supply the plurality of fractions to the column selection module in a sequential order.   
     
     
         9 . The dual online multidimensional liquid chromatography system according to  claim 8 , wherein the sample fractionation module includes:
 a first fractionation valve connected to the sample supply module, into which the sample is introduced;   a second fractionation valve provided adjacent to the first fractionation valve; and   a plurality of fraction storage loops provided corresponding to a number of the plurality of unit fractionation intervals within the unit sample supply time, each having one end connected to the first fractionation valve and the other end connected to the second fractionation valve, to concatenate and store the sample supplied during the corresponding unit fractionation intervals within each of the unit sample supply times in a sequential order.   
     
     
         10 . The dual online multidimensional liquid chromatography system according to  claim 9 , wherein the first fractionation valve includes:
 a first fraction inlet port through which the sample is introduced from the sample supply module;   a plurality of first fraction storage loop connection ports provided adjacent to the first fraction inlet port, to which one end of the plurality of fraction storage loops is each connected; and   a first connecting channel connecting the fraction inlet port and one of the plurality of first fraction storage loop connection ports in communication with each other corresponding to the unit fractionation interval, and   the second fractionation valve includes:   a plurality of second fraction storage loop connection ports to which the other end of the plurality of fraction storage loops is each connected;   a first fraction outlet port provided adjacent to the plurality of second fraction storage loop connection ports, the first fraction outlet port to which the other end of one of the plurality of fraction storage loops is connected to discharge the fraction; and   a second connecting channel connecting the first fraction outlet port and one of the plurality of second fraction storage loop connection ports in communication with each other corresponding to the unit fractionation interval.   
     
     
         11 . The dual online multidimensional liquid chromatography system according to  claim 10 , wherein the sample supply module includes:
 a first sample supply valve having a first sample inlet port connected to a sample injector, a first sample outlet port provided adjacent to the first sample inlet port, a first solvent inlet port connected to a first pump, a first solvent outlet port provided adjacent to the first solvent inlet port, and a first sample storage loop connection port and a second sample storage loop connection port to which two ends of a sample storage loop are each connected; and   a second sample supply valve having a second sample inlet port connected to the first solvent outlet port, a second sample outlet port provided adjacent to the second sample inlet port and connected to the first fraction inlet port, and a sample separation column having two ends, each connected to the second sample inlet port and the second sample outlet port, so that the sample is eluted at the second sample outlet port.   
     
     
         12 . The dual online multidimensional liquid chromatography system according to  claim 10 , wherein the column selection module includes:
 a column equilibration valve connected to the first fraction outlet port to provide a channel through which the plurality of fractions is supplied to the first solid phase extraction column or the second solid phase extraction column in alternating manner, and to equilibrate the first solid phase extraction column and the first reversed-phase liquid chromatography column or the second solid phase extraction column and the second reversed-phase liquid chromatography column in alternating manner; and   a column selection valve connected to the column equilibration valve to receive the supply of the plurality of fractions and supply the plurality of fractions to the first solid phase extraction column or the second solid phase extraction column in alternating manner, so that the fraction is eluted with the first reversed-phase liquid chromatography column in the first solid phase extraction column or the second reversed-phase liquid chromatography column in the second solid phase extraction column.   
     
     
         13 . The dual online multidimensional liquid chromatography system according to  claim 12 , wherein the column equilibration valve includes:
 a second fraction inlet port connected to the first fraction outlet port and a second pump which supplies a second solvent;   a third solvent inlet port connected to a third pump which supplies a third solvent, through which the third solvent is introduced;   a second fraction outlet port provided adjacent to the second fraction inlet port and selectively connected to the second fraction inlet port and the third solvent inlet port; and   a third solvent outlet port provided adjacent to the third solvent inlet port and selectively connected to the second fraction inlet port and the third solvent inlet port,   in a state that the second fraction inlet port and the third solvent outlet port are connected, the fraction into which the second solvent is injected is supplied to the first solid phase extraction column or the second solid phase extraction column via the column selection valve, and   in a state that the third solvent inlet port and the third solvent outlet port are connected, the third solvent equilibrates the first solid phase extraction column and the first reversed-phase liquid chromatography column or the second solid phase extraction column and the second reversed-phase liquid chromatography column in alternating manner via the column selection valve.   
     
     
         14 . The dual online multidimensional liquid chromatography system according to  claim 13 , wherein the column selection valve includes:
 a fraction and third solvent inlet port connected to the third solvent outlet port, through which the fraction or the third solvent is introduced;   a fourth solvent inlet port connected to a fourth pump which supplies a fourth solvent, through which the fourth solvent is introduced;   a fraction and third solvent outlet port provided adjacent to the fraction and third solvent inlet port and selectively connected to the fraction and third solvent inlet port and the fourth solvent inlet port; and   a fourth solvent outlet port provided adjacent to the fourth solvent inlet port and selectively connected to the fraction and third solvent inlet port and the fourth solvent inlet port,   as the fraction and third solvent inlet port and the fraction and third solvent outlet port are connected, the fraction is supplied to the first solid phase extraction column, and then in a state that the fourth solvent inlet port and the fraction and third solvent outlet port are connected, the fourth solvent elutes the fraction with the first reversed-phase liquid chromatography column in the first solid phase extraction column, and in a state that the fraction and third solvent inlet port and the fourth solvent outlet port are connected, the third solvent equilibrates the second solid phase extraction column and the second reversed-phase liquid chromatography column, and   as the fraction and third solvent inlet port and the fourth solvent outlet port are connected, the fraction is supplied to the second solid phase extraction column, and then in a state that the fourth solvent inlet port and the fourth solvent outlet port are connected, the fourth solvent elutes the fraction with the second reversed-phase liquid chromatography column in the second solid phase extraction column, and in a state that the fraction and third solvent inlet port and the fraction and third solvent outlet port are connected, the third solvent equilibrates the first solid phase extraction column and the first reversed-phase liquid chromatography column.   
     
     
         15 . The dual online multidimensional liquid chromatography system according to  claim 14 , wherein the dual column valve includes:
 a first solid phase extraction column connection port and a first solid phase extraction column channel port, each connected to two ends of the first solid phase extraction column;   a first solid phase extraction column inlet port connected to the fraction and third solvent outlet port, and selectively connected to the first solid phase extraction column connection port and the first solid phase extraction column channel port;   a first reversed-phase liquid chromatography column port connected to the first reversed-phase liquid chromatography column, and connected or disconnected to/from the first solid phase extraction column connection port;   a second solid phase extraction column connection port and a second solid phase extraction column channel port, each connected to two ends of the second solid phase extraction column;   a second solid phase extraction column inlet port connected to the fourth solvent outlet port, and selectively connected to the second solid phase extraction column connection port and the second solid phase extraction column channel port; and   a second reversed-phase liquid chromatography column port connected to the second reversed-phase liquid chromatography column, and connected or disconnected to/from the second solid phase extraction column connection port.   
     
     
         16 . The dual online multidimensional liquid chromatography system according to  claim 15 , wherein the dual column valve further includes:
 a first outlet port provided adjacent to the first solid phase extraction column channel port, and connected or disconnected to/from the first solid phase extraction column channel port; and   a second outlet port provided adjacent to the first outlet port, and connected or disconnected to/from the second solid phase extraction column channel port.