JPH0469748B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to chromatography devices such as liquid chromatography, supercritical fluid chromatography, and gas chromatography. [Prior art] Liquid chromatography (hereinafter referred to as "LC") and gas chromatography (hereinafter referred to as "GC")
) are used for the purpose of separating and purifying soluble substances and volatile substances, respectively, and are used in pharmaceutical, food,
Separation and separation on an industrial scale in fields such as fine chemistry
Applied to refining. Additionally, supercritical fluid chromatography (hereinafter referred to as "SFC") has also been developed for application to separation and purification. In conventional separation and purification methods such as LC, the sample, developing solution (gas),
An eluent (desorption gas) is introduced, the target component is developed and separated from other components or impurities, and a part of the effluent (gas) from the other end of the column is detected while the target component is separated from other components or impurities. It is configured to collect sequentially. In such conventional LC, the separation operation takes a long time, a large amount of developing solution, eluent, or carrier gas (developing gas, desorption gas) is required, and the recovery of the target component in the solution (vehicle) or gas is difficult. Since the concentration is low, it has the disadvantage that it is not easy to concentrate and recover the target component, and the cost of separation and purification is high, making it uneconomical. In order to solve the problem of separation and purification by LC, an adsorption/concentration column packed with a packing material that adsorbs the target component is installed at the outlet of the separation column, and after the target component is adsorbed to this column, the concentration A method has been proposed in which the concentration of the target component is increased by eluating and recovering the target component from a column for use.
However, such a method requires readjustment of the composition of the LC effluent to the concentration column flow conditions, requires regeneration of the concentration column with a column regenerating solution, and requires separation using a chromatography column and column for adsorption concentration. Since the operation is performed in two stages, the operation is complicated, and there are problems such as an increase in recovery loss and a decrease in the recovery rate, and it cannot be said to be an industrially advantageous method. In view of the above-mentioned circumstances, the present inventor proposed a chromatography device capable of efficiently separating target components in Japanese Patent Application Laid-Open No. 195451/1983. The chromatography apparatus according to JP-A-60-195451 divides the filler filling part into a plurality of unit filling parts, and each unit filling part is provided with a supply port and a discharge port, and the eluent, desorption gas, etc. The eluent is supplied only to a specific compartmentalized unit packing section to selectively recover target components. FIG. 2 is a flow path system diagram showing the configuration. In FIG. 2, the chromatography column section C has four columns C1 to C4 connected via flow path switching valves (six-way valves) VB2 to VB4. Further, this chromatography column section C is connected to a feeding section S by a feeding pipe H, and is also connected to a fractionating section T by a discharge pipe J. Each column C1 to C4 is connected via switching valves VB2 to VB4, and can flow liquid or gas in series with the next column, and can be separated to allow liquid or gas to flow in and out of one column. It is structured like this.
That is, flow path switching valves VA1 to VA4, VB1 to
VB4, VC1 to VC4 and the piping LA1 to LA between them
4, LB1 to LB8, and LC1 to LC4 are provided, and each column is configured to be either series (series) or independent by switching valves. Note that D is a detector for outflow fluid. According to this device, first, each column C1 to C4
are connected in series to inject and develop the sample solution, and after the target component forms a development zone in a specific column, the target component is recovered (eluted). For example, if the target component forms a development zone in columns C3 and C4, valves VA1 and VA3 and
The flow path of VB3 is switched and the eluent is selectively supplied only to columns C3 and C4. The eluate containing the target components from columns C3 and C4 is sent to the preparative separation section T via the pipe LB8 and the discharge pipe J, and is transferred to the desired preparative tanks T1 to TW by opening and closing the preparative valves VT1 to VTW. It is fractionated. [Problems to be Solved by the Invention] According to the chromatography apparatus disclosed in JP-A-60-195451, separation and purification can be carried out extremely efficiently, but there are an extremely large number of bubbles for switching channels. Because of this, there are problems with improvement, such as an increase in device configuration cost or a time-consuming operation. (For example, a total of 13 valves are used in the apparatus shown in FIG. A chromatography device comprising a column, two pumps for introducing fluid into the column, a fraction section having two fraction means, and a valve device for connecting the column, the pump, and the fraction section. It is. The first apparatus of the present invention includes a total of three chromatography columns 1, 2, and 3, first, second, and third, and two pumps P ₁ and P ₂ for introducing fluid into the columns. , a fraction section F comprising two fraction means F ₁ and F ₂ ;
A chromatography apparatus comprising a valve device 100 for connecting these columns, a pump, and a fraction section, the valve device comprising one six-way valve 10 and two four-way valves 30, 40, The six-way valve 10 has six ports 11, 12, 13, 14, 15, 16 arranged equally in the circumferential direction, and each port 11, 13, 15 is connected to the adjacent port 12, 14 in the clockwise direction. , 16, and each port 11, 13,
15 in the counterclockwise direction adjacent port 16,1
The four-way valves 30, 40 each have four ports 31, 32, 33 equally spaced in the circumferential direction. ,3
4, 41, 42, 43, 44, and flow path selection in which each port 31, 33, 41, 43 communicates only with the clockwise adjacent port 32, 34, 42, 44, and each port 31, 33,4
Port 3 adjacent to 1 and 43 in the counterclockwise direction
4, 32, 44, and 42, the pump _P1 is connected to the inlet of the first column 1, and the pump _P2 is connected to the four-way valve 30. The first port 11 of the six-way valve 10 is connected to the third port 33 of the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 32 of the four-way valve 30, and the fourth port 14 is connected to the inlet of the third column 3. The 5-port 15 is connected to the second port 42 of the four-way valve 40, the sixth port 16 is connected to the first port 31 of the four-way valve 30, and the fourth port 34 of the four-way valve 30 is connected to the fraction means _F1. The first port 41 of the four-way valve 40 is connected to the outlet of the column 2, the third port 43 is connected to the outlet of the column 3, and the fourth port 44 is connected to the fraction means _F2 . It is something to do. The second apparatus of the present invention includes a total of four chromatography columns 1, 2, 3, and 4, ie, first, second, third, and fourth, and two pumps P for introducing fluid into the columns. ₁ , P ₂ , a fraction section F including two fraction means F ₁ , F ₂ , and a valve device 100 for connecting these columns, pumps, and fraction sections, The valve device includes two six-way valves 10, 20 and 3.
The six-way valves 10, 20 each include six ports 11, 11, 13, 1 equally distributed in the circumferential direction.
4, 15, 16, 21, 22, 23, 24, 2
5, 26, and each port 11, 13,
15, 21, 23, 25 are connected only to the ports 12, 14, 16, 22, 24, 26 adjacent in the clockwise direction, and each port 11, 1
3, 15, 21, 23, and 25 are connected only to ports 16, 12, 14, 26, 22, and 24 that are adjacent to each other in the counterclockwise direction. The four-way valves 30, 40, and 50 each have four ports 31, 32, and 3 equally spaced in the circumferential direction.
3, 34, 41, 42, 43, 44, 51, 5
2, 53, 54, and each port 31,
33, 41, 43, 51, 53 in the clockwise direction adjacent ports 32, 34, 42, 44, 52,
Flow path selection to connect only to 54 and each port 3
1, 33, 41, 43, 51, 53 in the counterclockwise direction, adjacent ports 34, 32, 44, 42,
54, 52, the pump _P1 is connected to the inlet of the first column 1, and the pump _P2 is connected to the third port of the four-way valve 30. 33, and the first port 11 of the six-way valve 10 is connected to the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 22 of the six-way valve 20, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the six-way valve 20.
The third port 23 of the six-way valve 20 is connected to the second port 32 of the four-way valve 30, the fourth port 24 is connected to the inlet of the column 4, and the fifth port 25 is connected to the fourth port of the four-way valve 50. The second port 52 and the sixth port 26 are connected to the first port 31 of the four-way valve 30, and the fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 . The port 41 is connected to the outlet of the column 2, the third port 43 is connected to the outlet of the column 3, and the fourth port 44 is connected to the first port 51 of the four-way valve 50. is connected to the outlet of the column 4, and the fourth port 54 is connected to the fraction means _F2 . The third device of the present invention includes a total of five chromatography columns 1, 2, 3, 4, and 5: first, second, third, fourth, and fifth.
and two pumps P ₁ for introducing fluid into the column,
P ₂ , a fraction section F including two fraction means F ₁ and F ₂ , and a valve device 100 for connecting these columns, pumps, and fraction sections, the chromatography device comprising: The device consists of three six-way valves 10, 20, 60
and four four-way valves 30, 40, 50, 70, and the six-way valves 10, 20, 60 each have six ports 11, 12, 1 equally spaced in the circumferential direction.
3, 14, 15, 16, 21, 22, 23, 2
4, 25, 26, 61, 62, 63, 64, 6
5, 66, and each port 11, 13,
15, 21, 23, 25, 61, 63, 65 in the clockwise direction adjacent ports 12, 14, 16,
22, 24, 26, 62, 64, 66, and each port 11, 13, 15,
21, 23, 25, 61, 63, 65 in the counterclockwise direction adjacent ports 16, 12, 14, 2
The four-way valves 30, 40, 50, and 70 are each equally divided in the circumferential direction. 4 ports 31 arranged,
32, 33, 34, 41, 42, 43, 44, 5
1, 52, 53, 54, 71, 72, 73, 74
and each port 31, 33, 41, 4
Ports 32, 34, 42, 44, 52, 5 adjacent to ports 3, 51, 53, 71, 73 in a clockwise direction
Flow path selection to communicate only to ports 4, 72, 74 and each port 31, 33, 41, 43, 51, 53, 7
Port 3 adjacent to 1, 73 in the counterclockwise direction
4, 32, 44, 42, 54, 52, 74, 72
It has a rotary valve body that allows selection of a flow path to communicate only with the column, and the pump P ₁ is connected to the inlet of the first column 1, and the pump P ₂ is connected to the third port 33 of the four-way valve 30. The first port 11 of the six-way valve 10 is connected to the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 22 of the six-way valve 20, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the six-way valve 20.
The third port 23 of the six-way valve 20 is connected to the second port 62 of the six-way valve 60, the fourth port 24 is connected to the inlet of the column 4, and the fifth port 25 is connected to the fourth port of the four-way valve 50. The second port 52 is connected to the first port 61 of the six-way valve 60, and the third port 63 of the six-way valve 60 is connected to the second port 32 of the three-way valve 30. port 64
is connected to the inlet of the fifth column 5, the fifth port 65 is connected to the second port 72 of the four-way valve 70, and the sixth port 66 is connected to the first port 31 of the four-way valve 30. The fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 , the first port 41 of the four-way valve 40 is connected to the outlet of column 2, the third port 43 is connected to the outlet of column 3, The fourth port 44 is connected to the first port 51 of the four-way valve 50, the third port 53 of the four-way valve 50 is connected to the outlet of the column 4, and the fourth port 54 is connected to the first port of the four-way valve 70. The third port 73 of the four-way valve 70 is connected to the outlet of the column 5, and the fourth port 74 is connected to the fraction means _F2 . [Function] The chromatography apparatus of the present invention has either the following first or second column connection. First column connection: N columns are connected in series, and the outlet of the lowest column is connected to the fraction section. Second column connection: Among the N columns connected in series, the outlet of one of the columns upstream of the lowest column (hereinafter referred to as a branch column) is connected to the fraction section. Furthermore, when the second column connection is made, the valve device connects the second pump to the inlet of the column one stage lower than the branch column. As described above, the chromatography apparatus of the present invention can elute target components from a desired column, and since the number of valves installed is small, the cost of the apparatus configuration can be reduced and the operation can be simplified. [Examples] Examples of the present invention will be described in detail below with reference to the drawings. FIG. 1 is a system diagram illustrating a chromatography apparatus according to an embodiment of the present invention. The apparatus shown in FIG. 1 consists of columns 1 to 1 filled with N (four in this embodiment) connected in series, each having a fluid inlet at one end and a fluid outlet at the other end. It is equipped with 4. (N=4). Furthermore, this device includes two pumps P ₁ and P ₂ , a valve device 100, and a fraction section F. Pump P ₁ is connected to the inlet of column 1 and pump P ₂ is connected to valve arrangement 100 . Fraction section F has two fraction means.
It is equipped with F ₁ and F ₂ . The valve device 100 includes two (N-2=2) six-way valves 10, 20 and three (N-1=3) four-way valves 3.
It has a total of 5 valves, 0, 40, and 50. Next, the ports of each of the valves 10 to 50 and the connecting piping with columns, pumps, etc. will be explained. (In addition, from FIG. 1 and FIG. 5 onward, the piping is indicated by a thick solid line.) The six-way valve 10 includes six ports 11 to 16,
The first port 11 is connected to the outlet of column 1, the second port 12 is connected to the inlet of column 2, and the third port 13 is connected to the inlet of column 2.
is the second port 22 of the six-way valve 20, and the fourth port 1
4 is an inlet of the column 3, the fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port 21 of the six-way valve 20. Among the ports 21 to 26 of the six-way valve 20, the third port 23 is connected to the second port 32 of the four-way valve 30, the fourth port 24 is connected to the inlet of the column 4, and the fifth port 25 is connected to the inlet of the column 4.
is the second port 52 of the four-way valve 50, and the sixth port 2
6 is connected to the first port 31 of the four-way valve 30. Among the ports 31 to 34 of the four-way valve 30, the third port 33 is connected to _P2 , and the fourth port 34 is connected to the fraction means _F1 . Port 41 of the four-way valve 40 is connected to the outlet of column 2, port 43 is connected to the outlet of column 3, and port 43 is connected to the outlet of column 3.
4 is connected to the first port 51 of the four-way valve 50. The third port 53 of the four-way valve 50 is connected to the outlet of the column 4, and the fourth port 54 is connected to the fraction means _F2 . Thus, each port of each valve 10-50 is communicated with either the adjacent left or right port. That is, the six-way valves 10, 20, 60 and the four-way valves 30, 40, 50, 70 are each formed by a rotary valve body inserted into a cylindrical valve case. The valve cases of the six-way valves 10, 20, and 60 each have six ports 11 to 1 at six equal positions in the circumferential direction.
6, 21-26, and 61-66 are provided.
The valve cases of the four-way valves 30, 40, 50, and 70 have four ports 31 to 34, 41 to 44, 51 to 54, and 71 to 7 at four equal positions in the circumferential direction, respectively.
4 is provided. As shown in FIGS. 3 and 4, the rotary valve body inserted into the valve case is provided with a flow path so as to communicate between two adjacent ports. Therefore, as shown in FIGS. 3 and 4A, for example, the ports 11, 13, 15, 32, 34 of the six-way valve 10 and the four-way valve 30 are connected to the adjacent ports 16, 12, 1 in the counterclockwise direction.
Flow path selection A that communicates with ports 11, 13, 15, and 3 as shown in Figures 3 and 4 B.
2, 34 in the clockwise direction adjacent ports 12,
Flow path selection B communicating with 14, 16, 33, 31
can be made to take. Although not shown in enlarged view, the six-way valves 20, 60 and the four-way valves 40, 5
Similar flow path selections A and B can be made for 0 and 70 as well. An example of a method for separating and purifying a fluid to be separated using the apparatus shown in FIG. 1 will be described below with reference to FIGS. 5 and subsequent figures. Injection and development of sample liquid As in case No. 1 in Table 1, six-way valves 10 and 2
0, four-way valves 30 to 50 are set to flow path selection A. Then, the flow path configuration will be as shown in Figure 1, and the developing solution from pump _P1 will flow into column 1.
is supplied to After the developing solution leaves column 1,
Ports 11 and 16 of the six-way valve 10, ports 21 and 26 of the six-way valve 20, ports 31 and 32 of the four-way valve 30, ports 23 and 22 of the six-way valve 10,
The column 2 is reached through ports 13 and 12 of the six-way valve 10. After exiting the column 2, the developing solution further reaches the column 3 via ports 41 and 42 of the four-way valve 40 and ports 15 and 14 of the six-way valve 10. , 44, ports 51 and 52 of the four-way valve 50, and ports 25 and 24 of the six-way valve 20 to reach the column 4. and,
After exiting column 4, port 53 of four-way valve 50,
54 into the flanking means _F2 . After starting to pass the developing solution, a sample is injected using a loop injector or the like to perform development. As the developing solution passes through, each component in the sample is gradually developed in columns 1 to 4. Recovery of Target Component After the target component forms a development band on a specific column by developing the sample, the target component is recovered (eluted). The following cases No. 5 to 10 are adopted for this elution. Case No. 5 As shown in Figure 5 and Case No. 5 in Table 1, the flow path is switched so that only the four-way valve 30 becomes the flow path B, and then when pump P ₁ is operated, the elution Liquid is pump P ₁ → Column 1 → Ports 11, 16
→ Ports 21, 26 → Ports 31, 34 → and reaches the fraction means _F1 . At this time, when pump P ₂ is activated, the eluent flows from pump P ₂ → ports 33, 32 → ports 23, 2
2 → Port 13, 12 → Column 2 → Port 41,
42 → Port 15, 14 → Column 3 → Port 4
3, 44 → Port 51, 52 → Port 25, 24
→ Column 4 → Ports 53 and 54, and reaches the fraction means _F2 . Therefore, as shown in the "Number of Columns and Division Positions" column of Table 1, column 1 and columns 2 to 4 can be eluted simultaneously. (In this case, column 1 becomes the branch column.) After collecting the target component, if necessary, eluent is passed through columns 1 and 2 to 4 to remove impurities or other substances adsorbed on these parts. Collect the target component. In this case, valves 10 to 40 are selected as flow path selection A,
The eluent may be passed in series through columns 1-4. Case No. 6 As shown in Case No. 6 in FIG. 6 and Table 1, the six-way valve 10 and the four-way valve 30 are selected as flow path B, and the others are selected as flow path A. Then, the eluent from pump P ₁ is pump P ₁ → column 1 → ports 11, 12 → column 2
→Ports 41, 42 → Ports 15, 16 → Ports 21, 26 → Ports 31, 36 → Fraction means _F1 . Also, the eluent from pump P ₂ is
Pump P ₂ → Port 33, 32 → Port 23, 2
2 → Port 13, 14 → Column 3 → Port 43,
44 → Ports 51, 52 → Ports 25, 24 → Column 4 → Ports 53, 54 → Fraction means
Flows with F ₂ . Therefore, columns 1, 2 and 3, 4 can be eluted separately and simultaneously. Case No. 7 As shown in case No. 7 in FIG. 7 and Table 1, the six-way valve 20 and the four-way valve 30 are selected as flow path B, and the others are selected as flow path A. Then, the eluent from pump P ₁ is pump P ₁ → column 1 → ports 11, 16 → port 2
1, 22 → Port 13, 12 → Column 2 → Port 41, 42 → Port 15, 14 → Column 3 → Port 43, 44 → Port 51, 52 → Port 25,
26 → Port 31, 36 → Fraction means F ₁
It flows. Also, the eluent from pump P ₂ is pumped P ₂ → ports 33, 32 → ports 23, 24
→ Column 4 → Ports 53, 54 → Fraction means _F2 . Therefore, columns 1, 2, 3 and 4 can be eluted separately and simultaneously. Case No. 8 As shown in Figure 8 and Case 8 in Table 1, four-way valve 3
0 and 50 are the flow path selections for B, and the others are the flow path selections for A. Then, the eluent from pump P ₁ is pump P ₁ → column 1 → ports 11, 16 → port 2
1, 26 → Port 31, 36 → Fraction means
Flows with F ₁ . Also, the eluent from pump P ₂ is
Pump P ₂ → Port 33, 32 → Port 23, 2
2 → Ports 13, 12 → Ports 23, 22 → Ports 13, 12 → Column 2 → Ports 41, 42 → Ports 15, 14 → Column 3 → Ports 43, 44 →
It flows from ports 51 and 54 to fraction means _F2 . Therefore, columns 1, 2, and 3 can be eluted separately and simultaneously. Case No. 9 As shown in case No. 9 in FIG. 9 and Table 1, the six-way valve 10 and four-way valves 30 and 50 are selected as flow path B, and the others are selected as flow path A. Then, the eluent from pump P ₁ is pump P ₁ → column 1 → ports 11, 12 → column 2
→Ports 41, 42 → Ports 15, 16 → Ports 21, 26 → Ports 31, 36 → Fraction means _F1 . Also, the eluent from pump P ₂ is
Pump P ₂ → Port 33, 32 → Port 23, 2
2 → Port 13, 14 → Column 3 → Port 43,
44 → Ports 51, 54 → Fraction means F ₂
It flows. Therefore, columns 1, 2 and 3 can be eluted separately and simultaneously. Case No. 10 As shown in Case No. 10 in Figure 10 and Table 1, four-way valves 30, 40, and 50 are selected as flow path B, and the others are selected as flow path A.
The flow path selection is as follows. Then, the eluent from pump P ₁ is pump P ₁ → column 1 → ports 11, 16 → port 2
1, 26 → Port 31, 36 → Fraction means
Flows with F ₁ . Also, the eluent from pump P ₂ is
Pump P ₂ → Port 33, 32 → Port 23, 2
2 → Port 13, 12 → Column 2 → Port 41,
44→port 54→fraction means _F2 . Therefore, columns 1 and 2 can be eluted separately and simultaneously. As in Case Nos. 5 to 10 above, the device of this embodiment can elute the target component from any of the four columns. Further, even when columns 1 to 4 are divided into two at any position between columns 1 to 4, elution can be performed simultaneously in the two compartments, upstream and downstream of the division position. In addition, case No. 7 pump P ₁ → columns 1, 2,
When the flow path is selected as 3→fraction means F ₁ and the sample is supplied to the flow path, it can also be used as a chromatography device consisting of only three columns (columns 1, 2, and 3). Similarly, case No. 6 or 9 can be used as a chromatography device consisting of two columns (columns 1 and 2), and case No. 5, 8, or 10 can be used as a chromatography device consisting of one column (columns 1 and 2). It can be used as a chromatography device consisting of column 1). Since the number of valves to be operated when making the above-mentioned flow path selection is small, the operation is extremely easy. Next, there are 3 and 5 columns (N=3 or 5)
The configuration of the embodiment apparatus in this case is shown in FIGS. 11 and 12. In the apparatus shown in FIG. 11, one (N-2=
The six-way valve 10 of 1) and two (N-1=2) four-way valves 30, 40 are used, and in the device shown in FIG. ，
60 and four (N-1=4) four-way valves 30,4
0, 50, and 70 are used. In FIG. 11, a total of three chromatography columns 1, 2, and 3, a first, a second, and a third,
Two pumps P ₁ , P ₂ for introducing fluid into the column
, a fraction section F including two fraction means F ₁ and F ₂ , and a valve device 100 for connecting these columns, pumps, and fraction sections. The valve device includes one six-way valve 10 and two four-way valves 30 and 40. The six-way valve 10 has six ports 11, 12, 13, 14, 15, 16 equally distributed in the circumferential direction, and the four-way valves 30, 40 each have
Four ports 31, 3 equally distributed in the circumferential direction
2, 33, 34, 41, 42, 43, 44. Pump P ₁ is connected to the inlet of the first column 1, and pump P ₂ is connected to the third port 33 of the four-way valve 30.
It is connected to the. The first port 11 of the six-way valve 10 is connected to the first column 1
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 32 of the four-way valve 30, and the fourth port 14 is connected to the inlet of the third column 3. The 5-port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port 21 of the four-way valve 30. The fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 . The first port 41 of the four-way valve 40 is connected to the outlet of the column 2, the third port 43 to the outlet of the column 3, and the fourth port 44 to the first port 51 of the four-way valve 50. In FIG. 12, a total of five chromatography columns 1, 2, 3, 4, and 5, ie, first, second, third, fourth, and fifth, and two chromatography columns for introducing fluid into the columns are shown. There are installed pumps P ₁ and P ₂ , a fraction section F that includes two fraction means F ₁ and F ₂ , and a valve device 100 that connects these columns, the pumps, and the fraction section. The valve device includes three six-way valves 10, 20, 60.
and four four-way valves 30, 40, 50, and 70. The hexagonal valves 10, 20, 60 each have six ports 11, 12, 1 equally spaced in the circumferential direction.
3, 14, 15, 16, 21, 22, 23, 2
4, 25, 26, 61, 62, 63, 64, 6
5, 66, and the four-way valves 30, 40, 5
0 and 70 are four ports 31, 32, 33, 34, 41, and 4 equally spaced in the circumferential direction, respectively.
2, 43, 44, 51, 52, 53, 54, 7
1, 72, 73, 74. Pump P ₁ is connected to the inlet of the first column 1 , and pump P ₂ is connected to the third port 33 of the four-way valve 30 . The first port 11 of the six-way valve 10 is connected to the first column 1
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 22 of the six-way valve 20, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the six-way valve 20.
They are connected to ports 21, respectively. The third port 23 of the six-way valve 20 is connected to the third port 62 of the six-way valve 60, the fourth port 24 is connected to the inlet of the column 4, the fifth port 25 is connected to the second port 52 of the four-way valve 50, and the sixth port 26 are connected to the first port 61 of the six-way valve 60, respectively. The third port 63 of the six-way valve 60 is connected to the second port 32 of the three-way valve 30, and the fourth port 64
is connected to the inlet of the fifth column 5, the fifth port 65 is connected to the second port 72 of the four-way valve 70, and the sixth port 66 is connected to the first port 31 of the four-way valve 30. ing. The fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 . The first port 41 of the four-way valve 40 is connected to the outlet of the column 2, the third port 43 to the outlet of the column 3, and the fourth port 44 to the first port 51 of the four-way valve 51. The third port 53 of the four-way valve 50 is connected to the outlet of the column 4, and the fourth port 54 is connected to the first port 71 of the four-way valve 70. The third port 73 of the four-way valve 70 is connected to the outlet of the column 5, and the fourth port 74 is connected to the fraction means _F2 . By setting the number of columns and division positions in these devices as shown in Tables 2 and 3, elution from any column or simultaneous elution from a group of divided columns is possible, as in the above example. . In this embodiment, all the columns have the same dimensions. The sample always passes through column 1, so that column 1 deteriorates before the other columns. Therefore, if column 1 deteriorates, 1
By shifting the column one by one and inserting a new column in the column 4 position, you can replenish the column efficiently. Column 1 can also be used as a guard column. Further, in the present invention, the sample can be injected by using a loop injector or by connecting the pump _P1 to the sample container.

【table】

【table】

[Table] [Effects] As detailed above, the chromatography apparatus of the present invention uses a filler-filled section divided into a plurality of continuous unit-filled sections, and selectively performs the purpose-filling process from a specific unit-filled section. In devices designed to elute components, (a) The number of valves is small and operability is good. (b) Since there are two pumps and fractions, parallel processing is possible, reducing processing time. It has improved features such as: And the developing liquid (or developing gas) necessary for separation and purification,
The amount of eluent (or desorbed gas) can be reduced, making separation and
A compartment that can reduce purification costs and increase the concentration of target components in the eluate (or effluent gas), allowing post-processes such as concentration, crystallization, filtration, and drying to be performed efficiently. Separation and purification operations can be performed using a combination of different types of developing solution (or developing gas) and eluent (or desorption gas) for each zone, so the target component can be separated into a solution (or gas mixture) with the most appropriate composition. ), different types of fillers can be filled in each divided area, and a highly developed zone of the target component can be formed, thereby improving the recovery rate of the target component. It is possible to efficiently elute impurities developed in the column with a small amount of eluent (or desorption gas), and it is extremely easy to recover impurities. The time required for separation and purification is significantly shortened. If the fluid to be separated contains multiple target components and the movement speed of each target component is different, the development zone of each target component is formed in different areas, and elution (desorption) is performed in each zone. It is possible to achieve excellent effects such as the following, which is extremely advantageous industrially.

[Brief explanation of the drawing]

FIG. 1 is a system diagram explaining a chromatography device according to an embodiment of the present invention, FIG. 2 is a system diagram explaining a conventional device, FIGS. 3 and 4 are illustrations of valve operation, and FIG. 5 Each of the figures from FIG. 10 to FIG. 10 is an explanatory diagram of the operation of the embodiment apparatus, and FIGS. 11 and 12 are system diagrams illustrating different embodiment apparatuses. 1, 2, 3, 4, 5...column, 10, 20,
60...6-way valve, 30, 40, 50, 70...4-way valve.

Claims (1)

[Scope of Claims] 1 A total of three chromatography columns 1, 2, and 3, a first, second, and third, and two pumps P ₁ and P ₂ for introducing fluid into the columns, a fraction section F comprising two fraction means F ₁ and F ₂ ;
A chromatography apparatus comprising a valve device 100 for connecting these columns, a pump, and a fraction section, the valve device comprising one six-way valve 10 and two four-way valves 30, 40, The six-way valve 10 has six ports 11, 12, 13, 14, 15, 16 arranged equally in the circumferential direction, and each port 11, 13, 15 is connected to the adjacent port 12, 14 in the clockwise direction. , 16, and each port 11, 13,
15 in the counterclockwise direction adjacent port 16,1
The four-way valves 30, 40 each have four ports 31, 32, 33 equally spaced in the circumferential direction. ,3
4, 41, 42, 43, 44, and flow path selection in which each port 31, 33, 41, 43 communicates only with the adjacent port 32, 34, 42, 44 in the clockwise direction, and each port 31, 33,4
Port 3 adjacent to 1 and 43 in the counterclockwise direction
4, 32, 44, and 42, the pump _P1 is connected to the inlet of the first column 1, and the pump _P2 is connected to the four-way valve 30. The first port 11 of the six-way valve 10 is connected to the third port 33 of the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 32 of the four-way valve 30, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the four-way valve 30.
The fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 , the first port 41 of the four-way valve 40 is connected to the outlet of the column 2, and the third port 43 is connected to the column 2. 3 and the fourth port 44 are respectively connected to a fractionation means _F2 . 2 A total of four chromatography columns 1, 2, 3, and 4, the first, second, third, and fourth, and two pumps P ₁ and P ₂ for introducing fluid into the columns;
A chromatography apparatus comprising a fraction section F having two fraction means F ₁ and F ₂ , and a valve device 100 for connecting these columns, a pump, and the fraction section, wherein the valve devices include two pieces. Six-way valves 10, 20 and 3
The six-way valves 10, 20 each include six ports 11, 12, 13, 1 equally distributed in the circumferential direction.
4, 15, 16, 21, 22, 23, 24, 2
5, 26, and each port 11, 13,
15, 21, 23, 25 are connected only to the ports 12, 14, 16, 22, 24, 26 adjacent in the clockwise direction, and each port 11, 1
3, 15, 21, 23, 25 are adjacent to ports 16, 12, 14, 26, 22, in a counterclockwise direction.
The four-way valves 30, 40, and 50 each have four ports 31, 32, and 3 arranged equally in the circumferential direction.
3, 34, 41, 42, 43, 44, 51, 5
2, 53, 54, and each port 31,
33, 41, 43, 51, 53 in the clockwise direction adjacent ports 32, 34, 42, 44, 52,
Flow path selection to connect only to 54 and each port 3
1, 33, 41, 43, 51, 53 in the counterclockwise direction, adjacent ports 34, 32, 44, 42,
54, 52, the pump _P1 is connected to the inlet of the first column 1, and the pump _P2 is connected to the third port of the four-way valve 30. 33, and the first port 11 of the six-way valve 10 is connected to the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 22 of the six-way valve 20, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the six-way valve 20.
The third port 23 of the six-way valve 20 is connected to the second port 32 of the four-way valve 30, the fourth port 24 is connected to the inlet of the column 4, and the fifth port 25 is connected to the fourth port of the four-way valve 50. The second port 52 and the sixth port 26 are connected to the first port 31 of the four-way valve 30, and the fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 . The port 41 is connected to the outlet of the column 2, the third port 43 is connected to the outlet of the column 3, and the fourth port 44 is connected to the first port 51 of the four-way valve 50. A chromatography apparatus characterized in that F2 is connected to the outlet of column 4, and fourth port 54 is connected to fractionation means _F2 . 3 A total of 5 chromatography columns 1, 2, 3, 4, 5: first, second, third, fourth, and fifth
and two pumps P ₁ for introducing fluid into the column,
P ₂ , a fraction section F including two fraction means F ₁ and F ₂ , and a valve device 100 for connecting these columns, pumps, and fraction sections, the chromatography device comprising: The device consists of three six-way valves 10, 20, 60
and four four-way valves 30, 40, 50, 70, and the six-way valves 10, 20, 60 each have six ports 11, 12, 1 equally spaced in the circumferential direction.
3, 14, 15, 16, 21, 22, 23, 2
4, 25, 26, 61, 62, 63, 64, 6
5, 66, and each port 11, 13,
15, 21, 23, 25, 61, 63, 65 in the clockwise direction adjacent ports 12, 14, 16,
22, 24, 26, 62, 64, 66, and each port 11, 13, 15,
21, 23, 25, 61, 63, 65 in the counterclockwise direction adjacent ports 16, 12, 14, 2
The four-way valves 30, 40, 50, and 70 are each equally divided in the circumferential direction. 4 ports 31 arranged,
32, 33, 34, 41, 42, 43, 44, 5
1, 52, 53, 54, 71, 72, 73, 74
and each port 31, 33, 41, 4
3, 51, 53, 71, 73 in the clockwise direction adjacent ports 32, 34, 42, 44, 52, 5
Flow path selection to communicate only to ports 4, 72, 74 and each port 31, 33, 41, 43, 51, 53, 7
Port 3 adjacent to 1, 73 in the counterclockwise direction
4, 32, 44, 42, 54, 52, 74, 72
It has a rotary valve body that allows selection of a flow path to communicate only with the column, and the pump P ₁ is connected to the inlet of the first column 1, and the pump P ₂ is connected to the third port 33 of the four-way valve 30. The first port 11 of the six-way valve 10 is connected to the first column 1.
The second port 12 is connected to the inlet of the second column 2, the third port 13 is connected to the second port 22 of the six-way valve 20, and the fourth port 14 is connected to the inlet of the third column 3. The fifth port 15 is connected to the second port 42 of the four-way valve 40, and the sixth port 16 is connected to the first port of the six-way valve 20.
The third port 23 of the six-way valve 20 is connected to the second port 62 of the six-way valve 60, the fourth port 24 is connected to the inlet of the column 4, and the fifth port 25 is connected to the fourth port of the four-way valve 50. The second port 52 is connected to the first port 61 of the six-way valve 60, and the third port 63 of the six-way valve 60 is connected to the second port 32 of the three-way valve 30. port 64
is connected to the inlet of the fifth column 5, the fifth port 65 is connected to the second port 72 of the four-way valve 70, and the sixth port 66 is connected to the first port 31 of the four-way valve 30. The fourth port 34 of the four-way valve 30 is connected to the fraction means _F1 , the first port 41 of the four-way valve 40 is connected to the outlet of column 2, and the third port 43 is connected to the outlet of column 3. , the fourth port 44 is connected to the first port 51 of the four-way valve 50, the third port 53 of the four-way valve 50 is connected to the outlet of the column 4, and the fourth port 54 is connected to the first port of the four-way valve 70. A chromatography apparatus characterized in that the third port 73 of the four-way valve 70 is connected to the outlet of the column 5, and the fourth port 74 is connected to the fraction means _F2 . .