Automated fluid handling system
09709589 ยท 2017-07-18
Assignee
Inventors
Cpc classification
B01D17/12
PERFORMING OPERATIONS; TRANSPORTING
Y10T137/87885
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B01D29/60
PERFORMING OPERATIONS; TRANSPORTING
Y10T137/85986
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
Y10T137/6416
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
Y10T137/6851
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B01D15/10
PERFORMING OPERATIONS; TRANSPORTING
B01D15/08
PERFORMING OPERATIONS; TRANSPORTING
Y10T137/6525
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B01D2201/54
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01D35/00
PERFORMING OPERATIONS; TRANSPORTING
B01D15/10
PERFORMING OPERATIONS; TRANSPORTING
G01N35/10
PHYSICS
G01N30/88
PHYSICS
Abstract
Automated fluid handling system comprising a housing and two or more fluid handling units arranged as interchangeable modular components with an external fluidics section and an internal non fluidics section, and wherein the housing comprises a liquid handling panel with two or more of component positions for receiving said interchangeable modular components such that the external fluidics section is separated from the non fluidics section by the liquid handling panel.
Claims
1. An automated liquid chromatography system comprising a housing unit and at least four modular fluid handling units, wherein the housing unit comprises on one external side of the housing unit a plurality of receiving positions, each receiving position adapted to receive the modular fluid handling units therein such that a fluid handling section thereof is on the external side of the housing unit, the receiving positions being arranged in a two dimensional array, wherein each modular fluid handling unit is configured for insertion into the receiving positions of the housing unit, is readily interchangeable amongst similarly sized and shaped receiving positions of the housing unit, such that positioning of the modular fluid handling unit with respect to other modular fluid handling units permits a fluid flow path to be readily modified, wherein the fluid flow path is formed by fluidic connections between the modular fluid handling units, and includes a CPU for independently performing fluid control operations in response to instructions over a system BUS.
2. The automatic liquid chromatography system of claim 1, wherein the modular fluid handling units are each connected to the system BUS.
3. The automatic liquid chromatography system of claim 1, wherein the modular fluid handling units include a double piston pump, a sample pump, an inlet valve for selecting inlet fluid to a respective pump, an injection valve for injecting a sample onto a column connected to the flow fluid path of the liquid chromatography system, a column valve for connecting one of a plurality of columns to the flow fluid path, a UV-monitor, a mixer, a pH valve with an integrated flow cell for in-line monitoring of pH levels, a quaternary valve for automatic buffer preparation for formation of quaternary gradients, or any combination thereof.
4. The automatic liquid chromatography system of claim 1, further comprising an expansion housing unit that includes a plurality of receiving positions, each receiving position being adapted to receive the modular fluid handling units.
5. The automatic liquid chromatography system of claim 1, wherein the CPU automatically configures the modular fluid handling unit within the liquid chromatography system upon insertion into the receiving positions of the housing unit.
6. An automated liquid chromatography system comprising a housing unit and at least four freely arrangeable modular fluid handling units that control fluid flow through at least one chromatography column when fluidically interconnected to form a fluid flow path, wherein: the housing unit is adapted to receive the modular fluid handling units; the modular fluid handling units are adapted to fit into receiving positions of the housing unit, and each modular fluid handling unit includes a CPU for performing fluid control operations independently irrespective of the location within the housing unit; and a master control unit arranged to communicate through a system BUS to each fluid handling unit.
7. The automatic liquid chromatography system of claim 6, wherein said housing unit is adapted to accommodate at least one pump, at least one sensor unit and at least two fluid control valves of different configurations, of which at least two of the pump, the sensor unit, and the fluid control valves are freely arrangeable modular fluid handling units.
8. The automatic liquid chromatography system of claim 1, wherein the housing unit is adapted to accommodate at least one pump, at least one sensor unit and at least two fluid control valves of different configurations, of which at least two of the pump, the sensor unit, and the fluid control valves are arranged as modular fluid handling units.
9. The automatic liquid chromatography system of claim 8, wherein the at least two fluid control valves include an injection valve, a column valve with integrated pressure sensors, a quaternary valve, an inlet valve, a sample inlet valve, a pH valve, and an outlet valve.
10. The automatic liquid chromatography system of claim 1, wherein the fluid handling section of the modular fluid handling unit is sealed from an internal side of the housing unit when received in a receiving position of the housing unit.
11. The automatic liquid chromatography system of claim 1, wherein the modular fluid handling units are of the same size.
12. The automatic liquid chromatography system of claim 1, wherein the modular fluid handling units are of two or more sizes.
13. The automatic liquid chromatography system of claim 1, wherein the automatic liquid chromatography system further comprises a pH electrode that is external to the housing unit, and wherein the pH electrode is connected to a pH valve arranged as a modular fluid handling unit.
14. The automatic liquid chromatography system of claim 13, wherein the pH valve includes an integrated flow cell for in-line monitoring of pH levels.
15. The automatic liquid chromatography system of claim 1, wherein the modular fluid handling units include two double piston pumps, one injection valve for injecting sample onto a column connecting a flow path of the liquid chromatography system, a UV monitor, and a mixer.
16. The automatic liquid chromatography system of claim of claim 15, wherein the automatic liquid chromatography system further includes a column valve comprising pressure sensors integrated into inlet an outlet ports of the column valve for measuring the actual pressure over the connected column.
17. The automatic liquid chromatography system of claim of claim 15, wherein the automatic liquid chromatography system further includes a sample inlet valve.
18. The automatic liquid chromatography system of claim of claim 15, wherein the automatic liquid chromatography system further includes a conductivity monitor.
19. The automatic liquid chromatography system of claim 7, wherein the at least two fluid control valves include an injection valve, a column valve with integrated pressure sensors, a quaternary valve, an inlet valve, a sample inlet valve, a pH valve, and an outlet valve.
20. The automatic liquid chromatography system of claim 6, wherein the modular fluid handling unit includes one or more fluid connectors for connecting the modular fluid handling unit to the fluid path and wherein all fluid connectors are on an external side of the housing unit when the modular fluid handling unit is fitted into a receiving position of the housing unit.
21. The automatic liquid chromatography system of claim 20, wherein the fluid handling section of the modular fluid handling unit is sealed from an internal side of the housing unit when fitted in a receiving position of the housing unit.
22. The automatic liquid chromatography system of claim 6, wherein the modular fluid handling units are of the same size.
23. The automatic liquid chromatography system of claim 6, wherein the modular fluid handling units are of two or more sizes.
24. The automatic liquid chromatography system of claim 6, wherein the automatic liquid chromatography system further comprises a pH electrode that is external to the housing unit, and wherein the pH electrode is connected to a pH valve arranged as a modular fluid handling unit.
25. The automatic liquid chromatography system of claim 24, wherein the pH valve includes an integrated flow cell for in-line monitoring of pH levels.
26. The automatic liquid chromatography system of claim 6, wherein the modular fluid handling units include two double piston pumps, one injection valve for injecting a sample onto a column connecting a flow path of the liquid chromatography system, a UV monitor, and a mixer.
27. The automatic liquid chromatography system of claim of claim 26, wherein the automatic liquid chromatography system further includes a column valve comprising pressure sensors integrated into inlet and outlet ports of the column valve for measuring the actual pressure over the connected column.
28. The automatic liquid chromatography system of claim of claim 26, wherein the automatic liquid chromatography system further includes a sample inlet valve.
29. The automatic liquid chromatography system of claim 26, wherein the automatic liquid chromatography system further includes a conductivity monitor.
30. The automatic liquid chromatography system of claim 6, wherein the receiving positions of the housing are arranged in a two dimensional array.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1) The invention will be described in detail below with reference to the drawings, in which
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DETAILED DESCRIPTION OF THE INVENTION
(12) According to one embodiment, there is provided an automated fluid handling system comprising a housing and two or more fluid handling units arranged as interchangeable modular components with an external fluidics section and an internal non fluidics section, and wherein the housing comprises a liquid handling panel with two or more of component positions for receiving said interchangeable modular components such that the external fluidics section is separated from the non fluidics section by the liquid handling panel.
(13) According to another embodiment, there is provided a fluid handling system in the form of a liquid chromatography system comprising a housing, two or more high pressure pumps, at least one sensor unit and a plurality of fluid control valves of at least two different configurations, wherein at least the fluid control valves are arranged as interchangeable modular components and the housing comprises a liquid handling panel with a plurality of component positions for receiving said modular components.
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(15) The disclosed embodiment is supplied with three high precision pumps 7, 10, 12. There are two System pumps 7, 10, System pump A 10 and System pump B 7, and one Sample pump 12. The System pumps 7, 10 may be used individually, or in combination to generate isocratic or gradient elution in purification methods. The Sample pump 12 is dedicated for direct loading of sample onto a column, or for filling of sample loops.
(16) Function of the Pumps
(17) Each pump module consists of two pump heads (not shown). The individual heads are identical but actuated in opposite phase to each other by individual stepper motors, controlled by a microprocessor. The two pistons and pump heads work alternately to give a continuous, low pulsation, liquid delivery. The flow rate of the two System pumps may be varied between about 0.001 ml/min and 25.000 ml/min and the maximum operating pressure is about 20 MPa. The flow rate of the Sample pump may e.g. be varied between 0.01 and 25 ml/min and according to one embodiment the maximum operating pressure is 10 MPa.
(18) According to one embodiment, the plurality of fluid control valves of at least two different configurations are valves of rotary type. Such a motorized rotary valve may consist of a Valve head with a number of defined bores with channels to the inlet and outlet ports of the valve. The Rotary disc, mounted on the motor, has a number of defined channels. The pattern of channels of the Rotary disc together with the pattern and location of the ports of the Valve head, define the flow path and function of each type of valve. When the Rotary disc turns, the flow path in the valve changes.
(19) One embodiment of fluid control valves are Inlet valves A and B (9, 6 respectively) that are used to select which buffers or samples to use in a run, and Sample inlet valve 15 that is located before Sample pump 12. Inlet valve A 9 1 is located before System pump A 10, Inlet valve B 6 is located before System pump B 10, and Sample inlet valve 15 is located before Sample pump 12. Inlet valve A and Inlet valve B are connected to another embodiment of a fluid control valve in the form of a Quaternary valve 5. The Quaternary valve is used for automatic buffer preparation, and for formation of quartenary gradients. The number of inlets can be increased by installing component modules with extra inlet valves. Inlet valve A and Inlet valve B enable automatic changing between different buffers and wash solutions, and can be used to generate gradients by mixing buffer A and buffer B. The air sensors integrated in Inlet valve A and Inlet valve B can be used to prevent introduction of air into the pumps and columns.
(20) The Quarternary valve is used for automatic mixing of four different solutions. The Quaternary valve opens one inlet port at a time, and the different solutions are mixed in a Mixer 14 to form the desired buffer. The opening time in the switching valve is controlled by the system. The volume for each inlet port opening increases stepwise when the flow increases. To obtain a homogeneous buffer composition, one has to make sure to use a mixer chamber volume suitable for the flow rate of the method.
(21) The Quaternary valve can be used to create a gradient using four different solutions simultaneously in any combination. The percentage of each solution is controlled by instructions in the method. It is possible to form gradients that changes the percentage of two, three or four solutions linearly over time. This is useful when advanced methods are developed.
(22) The Sample inlet valve 15 enables automatic loading of different samples when using the Sample pump 12 to inject sample directly onto the column or to fill a sample loop. The Sample inlet valve has an inlet dedicated for buffer. This Buffer inlet is used in methods to fill the Sample pump with solution before sample is introduced. The Buffer inlet is also used to wash the Sample pump with buffer between runs. The air sensor integrated in the Sample inlet valve is e.g. used when sample is applied from a vessel onto a column by selecting Inject all sample using air sensor in the Sample application phase of a method. This function uses the Buffer inlet is used to finalize sample injection and to remove air from the Sample pump.
(23) Still another embodiment of fluid control valve may be an Injection valve 1, which is used to direct sample onto the column. The valve enables usage of a number of different sample application techniques. A sample loop can be connected to the Injection valve and filled either automatically using the Sample pump or manually using a syringe. The sample can also be injected directly onto the column using the Sample pump.
(24) Still another embodiment of fluid control valve may be a Column valve 2 that is used for connection of columns to the system, and to direct the flow onto the column Up to five columns can be connected to the disclosed embodiment of said valve simultaneously. The valve also has a built-in bypass capillary that enables bypassing of connected columns.
(25) The number of column positions can be increased by installing an extra Column valve. Both top and bottom of each column shall be connected to the Column valve. The top of the column shall be connected to one of the A ports (e.g., 1A), and the bottom of the column shall be connected to the corresponding B port (e.g., 1B). The flow direction can be set either from the top of the column to the bottom of the column, Down flow, or from the bottom of the column to the top of the column, Up flow. In the default flow path of the Column valve the columns are bypassed. Pressure monitors that measures the actual pressure over the column are integrated into the inlet and outlet ports of the Column valve.
(26) Still another embodiment of fluid control valve may be a pH valve 17 that has an integrated flow cell where a pH electrode can be installed. This enables in-line monitoring of pH during the run. A flow restrictor is connected to the pH valve and can be included in the flow path to generate a backpressure high enough to prevent formation of air bubbles in the UV flow cell. The pH valve is used to direct the flow to the pH electrode and to the flow restrictor, or to bypass one or both.
(27) Still another embodiment of fluid control valve may be an Outlet valve 18 that is used to direct the flow to a Fraction collector (not shown), to any of e.g. 10 outlet ports, or to waste. The number of outlets can be increased by installing an extra Outlet valve.
(28) A Mixer 14 may e.g. be located after System pump A and System pump B and before the Injection valve. The purpose of the Mixer is to make sure that the buffers from the System pumps are mixed to give a homogenous buffer composition. The Mixer has a built-in filter that prevents impurities from entering the flow path.
(29) To fulfill a desired purpose, with the disclosed liquid chromatography system it is possible to adapt and extend the flow path in a simple and a flexible way. Up to three extra fluid control valves or the like can be installed using the free valve positions. Dummy modules are installed in these positions at delivery. To obtain an optional flow path, it is also possible to move the standard fluid control valves to other positions. There are also two types of extra air sensors available which can be installed before Sample inlet valve or after Injection valve.
(30) In the configuration disclosed in
(31) In the configuration disclosed in
(32) In the configuration disclosed in
(33) Optional modules are easy to install in the disclosed modular liquid chromatography system. The dummy module is removed with a hexagon wrench and a bus cable is disconnected. The bus cable is connected to the optional fluid control valve or the like which is assembled in the instrument. The module is then added to the System properties in the control software. The available optional modules may e.g. be pre-configured to give the desired function. However, the function of a valve may e.g. be changed by changing the Node ID.
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(38) The liquid handling panel 22 of the fluid handling system may e.g. be designed in any suitable manner to allow the modular components to be arranged in an efficient manner.
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(44) According to one embodiment, different component modules are automatically identified by the master control unit, whereby they may be moved essentially freely between different positions. Moreover, the master control unit may be arranged to provide said information to Chromatography control software whereby experimental setup and planning may be performed. In one embodiment, the control system may be arranged to provide an optimized layout of the component modules with respect to the present layout of the liquid handling panel and available component modules for a specific experimental setup.
(45) According to one embodiment, the interchangeable panel sections 34 of
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