JP2808065B2 - Annular chromatography equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatography apparatus for isolating and purifying a target useful substance from a produced bulk in a process for producing various biochemical related useful substances. The present invention relates to a liquid chromatography apparatus that is easy to use.

[0002]

2. Description of the Related Art With the advance of biotechnology, various biochemical-related useful substances have been produced on an industrial scale. In these production processes, the target useful substance is isolated and purified from the produced bulk,
The process of making a product, that is, the downstream process, is important.

[0003] There are various separation techniques for isolating a desired useful substance from a produced bulk. Liquid chromatography apparatuses handle biochemical-related substances as the most useful technique. Widely used in fields such as food and dyes.

An annular chromatography apparatus is different from a column chromatography apparatus which performs batch operation.
It is characterized by continuous supply and separation operations.

[0005] Regarding the characteristics of the separation by the circular chromatography apparatus, for example, "Continuous separation using an annular chromatography apparatus having a rotating inlet / outlet" published by Goto et al.
nular chromatograph withrotating inlet and ou
tlet. M. Goto, S .; Goto,: J. Chem. Eng. Ja
p. , 20, 6, 599. 1987), with respect to separation components such as alcohols, amino acids, salts, saccharides, etc., by operating factors (for example, pH, feed rate, ratio of eluent, rotation speed, etc.) Engineering studies using a balance model have been conducted.

The basic structure and separation mechanism of a conventional circular chromatography apparatus are disclosed in JP-A-2-189458, JP-A-64-46749, and the like. No mention is made of a device mechanism related to maintenance such as cleaning in the filling cylinder.

[0007]

An annular chromatography apparatus comprises a packed cylinder main body comprising a chromatography apparatus substrate, an outer cylinder fixed on the chromatography apparatus substrate, and an inner cylinder built in the outer cylinder. It is an upper component, and the packed cylinder main body is attached to the chromatography apparatus table. The gap formed between the inner peripheral surface of the outer cylinder and the outer peripheral surface of the inner cylinder is filled with a separating agent (solid sorbent). Since the separating agent (solid sorbent) filled in the filling cylinder is usually changed regularly,
It is desired that the device mechanism be capable of easily performing maintenance operations such as replacement and cleaning of the filling cylinder.

[0008] The conventional annular chromatography apparatus has the following problems.

(A) Since the separation liquid processing section is provided inside the chromatography apparatus table (below the surface where the chromatography apparatus substrate is mounted), it is difficult to perform inspections. Unless it is disassembled, it cannot be sufficiently inspected and maintained.

(B) The outer cylinder 1 and the inner cylinder 2 for accommodating the separating agent (solid sorbent) are required to have a height of about 2 m in terms of function. In order to perform maintenance or replace the separating agent, it is necessary to pull out the outer cylinder or the inner cylinder in the upward direction. In order to extract the outer cylinder or inner cylinder upward, a space of 4 m or more, which is the sum of the heights of the outer cylinder and the inner cylinder, is required on the chromatography apparatus substrate, and the height from the floor to the apparatus substrate is required. If the height is assumed to be 0.5 m, a lifting height of at least 4.5 m is required.

(C) In order to extract the outer cylinder or the inner cylinder upward, it is necessary to prepare lifting equipment such as a crane and a tow truck.

(D) When removing the separating agent (solid sorbent), it is necessary to provide a device for collecting the separating agent.

An object of the present invention is to provide an annular chromatography apparatus which does not require a space for maintenance and inspection above the packed cylinder main body.

[0014]

SUMMARY OF THE INVENTION The object of the present invention is to provide an annular chromatography apparatus substrate, a cylindrical outer cylinder connected to the annular chromatography apparatus substrate, and a concentrically arranged inner cylinder inside the outer cylinder. An annular chromatography apparatus comprising: a filling cylinder main body including an inner cylinder forming an annular separating agent filling portion between the peripheral cylinder and a peripheral surface; and a chromatography apparatus table supporting the packing cylinder main body. A support arm having one end fixed to the annular chromatography apparatus substrate, an inclined drive shaft having the other end of the support arm fixed and arranged substantially horizontally, and a rotary drive motor that rotationally drives the inclined drive shaft. And the detachable coupling of the annular chromatography device substrate to the chromatography device table.

[0015] The above-mentioned problem is also caused by a problem that the annular chromatographic apparatus substrate and the cylindrical outer cylinder coupled on the annular chromatographic apparatus substrate and the inner peripheral surface of the outer cylinder concentrically arranged inside the outer cylinder. And a chromatography device table that supports the packing tube main body, which includes an inner cylinder forming an annular separating agent filling portion, and the annular chromatography device substrate includes the chromatography device table. An annular chromatography apparatus detachably coupled to the apparatus table, wherein the inclined drive shaft is disposed near the annular chromatography apparatus substrate of the chromatography apparatus table and rotatably supported on the chromatography apparatus table via a bearing. A support arm for connecting the inclined drive shaft and the filling cylinder, and a rotational drive of the inclined drive shaft. Also achieved by providing a rotary drive motor.

[0016]

After the coupling cylinder main body of the chromatography apparatus is released from the connection with the chromatography apparatus table, it is rotated by a rotary driving motor via a support arm connected to the packing cylinder main body and an inclined drive shaft coupled to the support arm. It is rotated 90-150 ° around the tilt drive shaft, and its posture is changed from a horizontal position to a position tilted downward. As a result, it is possible to disassemble and assemble the main body of the filling cylinder and take out the separating agent without providing an extra space for disassembling and checking above the apparatus and without providing a high-lifting equipment.

[0017]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is an elevational and cross-sectional view of an annular chromatography apparatus having a packed tube disassembling mechanism according to an embodiment of the present invention. The illustrated annular chromatography device is a disk-shaped chromatography device substrate 15 detachably fixed to an upper surface of a chromatography device table 40 by bolts 34, and is attached to the chromatography device substrate 15 by bolts 9 via a gasket 23. A cylindrical outer cylinder 1 and a cylindrical inner cylinder 2 which is provided concentrically with the outer cylinder 1 and is attached to the chromatographic apparatus substrate 15 by a bolt 50 via a gasket 23 similarly to the outer cylinder 1.
A gap formed between the inner peripheral surface of the outer cylinder 1 and the outer peripheral surface of the inner cylinder 2 for accommodating the separating agent 3, and an upper part fastened to the upper end of the outer cylinder 1 by bolts 8 Lid 5,
A raw material supply rotary shaft 25 inserted through the center of the upper lid 5 and supported on the upper surface of the upper lid via a ball bearing.
A rotation drive shaft 12 that is arranged in the center axis of the outer cylinder 5 and has an upper end coupled to a lower end of the raw material supply rotation shaft 25 and a lower end inserted into a center hole of the chromatography apparatus substrate 15. A rotary drive motor 14 coupled to the lower end of the rotary drive shaft 12 via a spline intermediate piece 11, and engaged with a serration fitted on the spline intermediate piece 11 and cut on the outer periphery of the spline intermediate piece 11. A circle bucket 19, which is connected to the lower surface of the chromatography apparatus table 40, a circle divider 21 having a drive shaft of the rotary drive motor 14 inserted through the center thereof, and a separated liquid or elution stored in the circle bucket 19. Transfer the liquid to the circle divider 21
, A separation liquid bottle 29 connected to the circle divider 21 by a separation liquid introduction pipe 28 with a stop valve 33 interposed, and a motor mounting for fixing the rotary drive motor 14 to the lower surface of the circle divider 21. Bracket 1
3, a material liquid supply nozzle unit 4 connected to the upper end of the material supply rotation shaft 25 via a swivel union 25B, a material liquid inlet 6 connected to the material liquid supply nozzle unit 4, and the upper lid 5, an eluent supply nozzle 7 for supplying an eluent to the separating agent filled in the gap, a pair of support arms 16 one end of which is fixed to the upper surface of the chromatography apparatus substrate 15, and the support arm 1
6 includes a tilt drive shaft 17 to which the other end is fixed, and a harmonic drive motor 32 coupled to the tilt drive shaft 17 via a coupling 31.

The inside of the inner cylinder 2 is divided into two concentric cylindrical sections, and a closed section on the outer peripheral side which is in contact with a space filled with the separating agent is used as a thermostat 24. As shown in FIG. 2, the chromatography apparatus substrate 15 includes a constant temperature liquid inlet nozzle 10-1 for supplying a constant temperature liquid to the constant temperature tank 24, and a constant temperature liquid outlet nozzle 10-2 for extracting the constant temperature liquid from the constant temperature tank 24. Is provided.

A large number of pores penetrating the chromatography device substrate 15 in the vertical direction are provided at a position below the gap portion of the chromatography device substrate 15 so that the separating agent filled in the gap portion can be removed. The liquid flowing down is dropped on a circle bucket rotating below. The circle bucket 19
Is supported at the center of a circle divider 21 via a ball bearing 20 fixed concentrically to the spline intermediate piece 11 at the center of the lower surface thereof and receiving an axial load. Further, the distribution pipe 27 is arranged so that its outlet comes to an upper part of any of a plurality of concentric grooves formed in the circle divider 21.

The inclined drive shaft 17 is disposed substantially horizontally on the upper surface of the chromatography device table 40, and is rotatably supported on the upper surface of the chromatography device table 40 via a bearing box 18 having a ball bearing 30 therein. I have.

The rotary drive motor 14 rotates the raw material supply rotary shaft 25 via the rotary drive shaft 12, and synchronously rotates the circle basket 19 via the spline intermediate piece 11. The raw material supply rotary shaft 25 is provided with a raw material nozzle 25A that is connected to the raw material liquid inlet 6 via a swivel union 25B and a raw material liquid supply nozzle unit 4. The outlet of the raw material nozzle 25A is located at a position where the sample to be separated is supplied from above to the layer of the separating agent filled in the gap while rotating.

An O-ring 26 is provided at the upper end of the outer cylinder 1, and the upper lid 5 is provided through the O-ring 26. When releasing the connection between the spline intermediate piece 11 and the rotary drive shaft 12, the motor mounting bracket 13 is removed, and the position of the rotary drive motor 14 is moved downward.

The stop valve 33 is opened when the separated liquid is collected in the separation bottle.

The height of the table from the floor of the annular chromatography apparatus of this embodiment is H1, the height of the outer cylinder of the packed cylinder main body containing the separating agent is H2, and the outer cylinder equipped with the supply nozzles for the raw material liquid and the eluent is provided. Assuming that the cylinder head height is H3, H1 = 500 mm H2 = 2,000 mm H3 = 500 mm, and the total height reaches 3,000 mm.

Assume that the height of the inner cylinder is H4 and that the height is 1,750 mm.
Then, in order to remove the inner cylinder or the outer cylinder, a space at least up to a height of 4,250 mm on the floor is required.

Next, the operation of the annular chromatography apparatus will be described. The eluent flows to the upper ends of the outer tube 1 and the inner tube 2 through the eluent supply nozzle 7 and flows down while filling the separating agent with the eluent, thereby causing the chromatographic device substrate 15 to flow.
And flows out to the circle bucket 19 through a number of small holes.

On the other hand, the sample to be separated (hereinafter referred to as the raw material liquid) reaches the raw material supply rotary shaft 25 from the raw material liquid inlet 6 through the raw material liquid supply nozzle unit 4 and the swivel union 25B.
Raw material nozzle 25 rotating around the axis of the filling cylinder
From A, it is fed from above to the separating agent layer. The supplied raw material liquid flows down while being in contact with the separating agent, and separates and flows out of the pores of the chromatography device substrate 15 while being separated into several components by the function of the eluent and the separating agent, and is dropped on the circle bucket 19. Inflow. The positions of the pores from which the separated components flow out change in synchronization with the rotation of the raw material nozzle 25A. However, the circle bucket 19 also rotates in synchronization with the rotation of the raw material nozzle 25A. Certain components (separated liquids) are always stored in the circle bucket 1
9 at a specific position (area).

The circle bucket 19 is divided into a plurality of sections, and the separated liquid and the eluent which have flowed in pass through distribution pipes 27 connected to the respective sections, so that the circle divider 2 is separated.
One corresponding section (groove). The separated liquid guided to each section of the circle divider 21 is transferred to and stored in a separated liquid bottle 29 through a separated liquid introduction pipe 28 having a stop valve 33. When an appropriate amount is stored, the stop valve 33 is closed, and the separated liquid is collected. The eluent is recovered from the outer cylindrical section of the circle divider 21 via the eluent recovery nozzle. These are shown as examples of simple devices, but in many cases automatic operations are actually performed.

Next, the maintenance and inspection in this embodiment will be described.

1) In the case of taking out, exchanging, checking and maintaining the separation agent, disconnect the piping connection of the raw material liquid inlet 6. The pipe connection of the eluent supply nozzle 7 is disconnected. Constant temperature liquid inlet / outlet nozzle (10-1, 2)
Remove. Flexible pipes are used for these pipes, and if the pipes are not overloaded even if the filling cylinder is inclined, they are left as they are. The motor mounting bracket 13 is removed, and the engagement between the rotary drive shaft 12 and the spline intermediate piece 11 is released. Alternatively, an uneven coupling is provided, and only the direction is confirmed to prepare for release. A support 53 for supporting the filling cylinder and a tray 52 for receiving the separating agent are arranged at the inspection position of the filling cylinder. The bolts 34 are removed in order to tilt the chromatography device substrate 15 attached to the chromatography device table 40.

After the bolt 34 is removed, the harmonic drive motor 32 is driven to rotate the filling cylinder main body around the inclined drive shaft 17, and the harmonic drive motor 32 is stopped at the inspection position, and the filling cylinder main body is removed. It is supported by a support 53. As can be understood from the above description, if the piping is made flexible so that no excessive force is applied to the piping even when the filling cylinder is inclined, the rotation drive motor can be operated only by disassembling the bolt 34. I can fulfill my purpose.

Thus, the portion attached to the outer cylinder head height H3 is released. When the bolt 8 tightening the upper lid 5 is released, the separating agent 3 is collected in the tray 52.
However, in order to prevent the separating agent from dropping naturally, it is necessary to open the upper lid at an inclination angle of about 45 ° and plug a gap into the space filled with the separating agent.

2) Inspection of Opening of Inner and Outer Cylinders A support stand or a table lifter 51 is arranged at a position where the filling cylinder is horizontal. In step 1), the filling cylinder is tilted to a horizontal position, and is supported by the support table or the table lifter 51. The bolt 8 is loosened and removed, and the bearing that supports the raw material supply rotating shaft 25 on the upper lid 5 is removed, and the upper lid 5 is removed. Remove the material nozzle 25A.
Remove the bolt 50 and pull out the inner cylinder 2 horizontally. Bolt 9
And move the outer cylinder 1 horizontally. The recovery of the inner cylinder and the outer cylinder is performed in the reverse order of the above procedure. After the inner cylinder and the outer cylinder have been assembled, the separating agent is supplied from above at a state where the filling cylinder is almost vertical.

3) Inspection of the Circle Bucket 19 and the Circle Divider 21 The circle bucket 19 and the circle divider 21 are provided below the chromatography apparatus substrate 15. Since these are located inside the chromatography apparatus table 40 and open upward, inspection from the side is difficult. In this embodiment, the chromatography apparatus substrate 1
5 and the outer cylinder 1 and the inner cylinder 2 are integrated into the inclined drive shaft 17.
Rotate around. Accordingly, the chromatography apparatus substrate 15 is opened upward with the rotation of the tilt drive shaft 17. In the chromatography device table 40, an opening approximately in the size of the circle divider 21 is formed.
If the circle bucket 19 is pulled out from the serration on the outer surface of the spline intermediate piece 11, the circle divider 21 can be easily inspected.

FIG. 2 is a sectional view taken along line AA of FIG.
A constant temperature liquid inlet nozzle 10-1 and a constant temperature liquid outlet nozzle 10-2 are provided on the outer periphery of the chromatography device substrate 15,
On the upper surface of the chromatography device substrate 15, a pair of support arms 16 used for tilting rotation of the packed cylinder are provided,
The tilt drive shaft 17 is fixed to the support arm 16. The inclined drive shaft 17 has a bearing 30 and a bearing box 18.
It is stored in. The tilt drive shaft 17 is a coupling 31
And the shaft of the harmonic drive motor 32 is connected. Reference numeral 9 denotes a bolt for fixing the outer cylinder 1 to the chromatography apparatus substrate 15.

FIG. 3 is a sectional view taken along the line BB of FIG.
The center of the tilt drive shaft 17 of FIG. 2 is located on the chromatography device table 40, and the harmonic drive motor 32 is coupled to the tilt drive shaft 17. These have the same axis. A bracket 41 is fixed to the back surface of the chromatography apparatus table 40 with bolts 42, and the bracket 41 is provided with a mounting seat for the harmonic drive motor 32. Harmonic drive motor 32
Is attached to the attachment seat with a bolt 43.

FIG. 4 shows a procedure for disassembling the outer cylinder or the inner cylinder by laying the outer cylinder or the inner cylinder horizontally when disassembling and inspecting or replacing the inner cylinder. Outer cylinder 1,
Alternatively, the inner cylinder 2 is placed on the table lifter 51 and removed while being shifted in the longitudinal direction. This is stored in a separate storage area and disassembled and assembled into the next inner cylinder. In this case, the upper lid 5 is removed when removing the separating agent. The disassembly and assembly of the outer cylinder 1 is performed by removing and installing the bolt 9.
In disassembly and assembly of the inner cylinder, the bolt 50 is detached and attached.

In the state shown in FIG. 4, the chromatography apparatus substrate 15 is opened almost vertically, and it can be seen that the inspection of the circle bucket 19 and the circle divider 21 inside the chromatography apparatus table 40 can be easily performed.

FIG. 5 shows a procedure for removing the separating agent from the filling cylinder.

The inclined drive shaft 17 is rotated by the harmonic drive motor 32 to incline the filling cylinder at an angle at which the separating agent easily flows out, and the outflowing separating agent is stored in the tray 52. In FIG. 5, a well 54 is provided on the floor surface, and a tray 52 is arranged in the well 54. The well serves to prevent the liquid from scattering on the floor, but the well may be omitted and a shallow wide tray may be provided.

According to the present embodiment, the following effects are obtained.

[0042] The solid filler filled between the outer cylinder and the inner cylinder can be easily replaced and completely removed from the inside.

. It is possible to quickly clean a gap formed between the inner peripheral surface of the outer cylinder and the outer peripheral surface of the inner cylinder and to discharge the residue after the cleaning.

[0044] Disassembly and mounting of components such as the inner cylinder, upper lid, and rotary drive shaft built in the packed cylinder main body of the chromatography apparatus can be performed in a simple posture with ordinary tools.

The chromatography apparatus substrate is opened at the same time as the outer cylinder and the inner cylinder, thereby facilitating inspection and cleaning of the circle bucket and the circle divider.

In the above embodiment, the filling cylinder is supported only by the support arm 16 during the inclined rotation. However, a roller is provided on the side surface near the center of gravity of the outer cylinder, and the locus of the roller when the filling cylinder is inclined and rotates. A guide rail may be provided along the axis, and a part of the weight of the filling cylinder may be supported by the guide rail via the roller during the inclined rotation of the filling cylinder.

[0047]

According to the present invention, the chromatography apparatus substrate, the outer tube, and the inner tube are integrally connected to each other, and are rotated around a tilt drive shaft arranged near the lower end of the outer tube. Therefore, it is not necessary to provide an extra space or a high-lifting equipment at the upper part of the apparatus for disassembling the outer cylinder and the inner cylinder, and it is easy to take out the filled separating agent.

[Brief description of the drawings]

FIG. 1 is a longitudinal sectional view showing an embodiment of the present invention.

FIG. 2 is a plan view showing a cross section taken along line AA of FIG. 1;

FIG. 3 is a front view showing a cross section taken along line BB of FIG. 2;

FIG. 4 is a side view showing an example of a position of a filling cylinder when an outer cylinder and / or an inner cylinder is removed in the embodiment shown in FIG. 1;

FIG. 5 is a side view showing an example of a position of a filling cylinder when taking out a separating agent in the embodiment shown in FIG.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 Outer cylinder 2 Inner cylinder 3 Separating agent 4 Raw material liquid supply nozzle unit 5 Upper lid 6 Raw material liquid inlet 7 Eluent liquid supply nozzle 8, 9 volts 10-1 Constant temperature liquid inlet nozzle 10-2 Constant temperature liquid outlet nozzle 11 Spline intermediate piece 12 Rotary drive shaft 12A Intermediate shaft 13 Motor mounting bracket 14 Rotary drive motor 15 Chromatography apparatus substrate 16 Support arm 17 Inclined drive shaft 18 Bearing box 19 Circle bucket 20 Ball bearing 21 Circle divider 24 Constant temperature bath 25 Raw material supply rotary shaft 25A Raw material nozzle 25B Swivel Union 26 O-ring 27-minute pipe 28 Separation liquid introduction pipe 29 Separation liquid bottle 30 Ball bearing 31 Coupling 32 Harmonic drive motor 33 Stop valve 34 Bolt 40 Chromatography apparatus table 41 Support table 4 , 43 bolt 50 bolt 51 table lifter 52 tray 53 support base 54 wells

Continuation of the front page (56) References JP-A-62-29753 (JP, A) JP-A-4-227027 (JP, A) JP-A 62-121555 (JP, U) JP-A 64-46749 (JP) , U) (58) Fields investigated (Int. Cl. ⁶ , DB name) G01N 30/60 B01D 15/08 G01N 30/02

Claims (2)

(57) [Claims] 1. An annular chromatography apparatus substrate, a cylindrical outer cylinder coupled on the annular chromatography apparatus substrate, and an annular ring formed between the outer cylinder inner peripheral surface and concentrically disposed inside the outer cylinder. An annular chromatography apparatus including a packing cylinder main body including an inner cylinder forming a separating agent filling portion, and a chromatography apparatus table supporting the packing cylinder main body; A fixed drive arm, an inclined drive shaft disposed substantially horizontally and the other end of the support arm is fixed,
A rotary drive motor for rotating the tilt drive shaft, the outer
The roller installed on the outer peripheral surface of the cylinder and the filling cylinder
When the roller is tilted around the oblique drive shaft as the rotation center,
Weight of the filling cylinder during the tilting of the filling cylinder, which is arranged along the trajectory
And a guide rail that supports a part of the
The axis of the outer cylinder including the axis of the inclined drive shaft
The distance between the plane parallel to the line and the axis of the outer cylinder is
At least the radius of the inclined drive shaft than the radius of the outer peripheral surface of
An annular chromatography apparatus substrate, wherein the annular chromatography apparatus substrate is detachably coupled to the chromatography apparatus table. 2. An annular chromatographic apparatus substrate, a cylindrical outer cylinder coupled on the annular chromatographic apparatus substrate, and an annular concentrically disposed inside the outer cylinder between an inner peripheral surface of the outer cylinder. A packing cylinder main body including an inner cylinder forming a separating agent filling section, and a chromatography apparatus table supporting the packing cylinder main body, wherein the annular chromatography apparatus substrate is attached to and detached from the chromatography apparatus table. An annular drive, the tilt drive shaft being disposed substantially horizontally near the toroidal chromatographic device substrate of the chromatographic device table and rotatably supported on the chromatographic device table via a bearing; A support arm for connecting the inclined drive shaft and the filling cylinder; and a rotary drive for rotating the inclined drive shaft. A prime mover and the outer cylinder
Roller and the filling cylinder rotate the inclined drive shaft
It is arranged along the trajectory of the roller when tilting as the center.
When the filling cylinder is tilted, a part of the weight of the filling cylinder is
And a guide rail supported through the roller.
A plane including the axis of the inclined drive shaft and parallel to the axis of the outer cylinder;
Distance between the outer cylinder and the axis of the outer cylinder is the radius of the outer peripheral surface of the outer cylinder.
Set larger than at least the radius of the inclined drive shaft
An annular chromatography apparatus characterized by being performed .