Automated fluid handling system
10598678 ยท 2020-03-24
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
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
B01D15/08
PERFORMING OPERATIONS; TRANSPORTING
International classification
G01N35/10
PHYSICS
B01D29/60
PERFORMING OPERATIONS; TRANSPORTING
B01D15/10
PERFORMING OPERATIONS; TRANSPORTING
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 comprising an external surface and two or more fluid handling unit receiving positions arranged in a two dimensional array on the external surface of the housing unit; and multiple fluid handling units corresponding in size and shape to the two or more fluid handling unit receiving positions, wherein at least one of the multiple fluid handling units when arranged in a corresponding fluid handling unit receiving position comprises (1) an external section that is external to the housing unit, and (2) an internal section that is internal to the housing unit, wherein the external section comprises one or more fluid connectors for connecting with a fluid flow path of the automated liquid chromatography system, and the internal section comprises an enclosure with one or more air inlet openings; wherein said automated liquid chromatography system is adapted to allow each fluid handling unit to be freely and independently positioned in any one of the fluid handling unit receiving positions of the housing unit.
2. The automated liquid chromatography system of claim 1, wherein the two dimensional array comprises at least two rows and at least two columns.
3. The automated liquid chromatography system of claim 1, wherein the two or more fluid handling unit receiving positions each include a connector for connecting each fluid handling unit to a system bus and wherein the fluid handling units each include a dedicated CPU allowing the fluid handling units to independently perform operations in response to instructions over a system bus.
4. The automated liquid chromatography system of claim 1, wherein the liquid chromatography system comprises a master control unit arranged to automatically detect fluid handling units when inserted into the fluid handling unit receiving positions.
5. The automated liquid chromatography system of claim 1, further comprising at least one dummy module.
6. The automated liquid chromatography system of claim 1, wherein the fluid handling units include at least one pump, at least one sensor unit and at least two fluid control valves of different configurations.
7. The automated liquid chromatograph system of claim 1, wherein the housing unit includes at least four fluid handling unit receiving positions.
8. The automated liquid chromatograph system of claim 1, wherein the liquid chromatography system further comprises at least one expansion housing module arranged to be attached to the housing unit, the at least one expansion housing module comprising at least two fluid handling unit receiving positions.
9. The automated liquid chromatograph system of claim 1, further comprising a master control unit that is arranged to automatically perform automatic configuration on the system.
10. The automated liquid chromatograph system of claim 1, wherein the liquid chromatography system further comprises a pH electrode that is external to the housing unit.
11. The automated liquid chromatograph system of claim 10, wherein the pH electrode is connected to a pH valve formed as a fluid handling unit.
12. The automated liquid chromatograph system of claim 3, wherein each fluid handling unit receiving position includes a complementary connector for connecting a bus connector of the fluid handling unit inserted therein to the system bus.
13. The automated liquid chromatograph system of claim 1, wherein the internal section of the at least one fluid handling unit comprises electronics, electrical components, or control means.
14. The automated liquid chromatograph system of claim 11, wherein the pH valve comprises an integrated flow cell for in-line monitoring of pH levels.
15. The automated liquid chromatograph system of claim 1, wherein the system further comprises a quaternary valve for automatic buffer preparation and formation of quaternary gradients formed as a fluid handling unit.
16. The automated liquid chromatograph system of claim 1, wherein the automated liquid chromatography system comprises a first fluid handling unit receiving position of a first size, and second fluid handling unit receiving position of a second size which is different than the first size, wherein fluid handling units of the same size are interchangeable with each other.
17. An automated liquid chromatography system comprising: a main housing unit comprising an external surface and two or more fluid handling unit receiving positions arranged in a two dimensional array on the external surface of the main housing unit; an expansion housing unit comprising an external surface and two or more fluid handling unit receiving positions adjacent to the external surface of the main housing unit; and multiple fluid handling units corresponding in size and shape to the two or more fluid handling unit receiving positions of the main housing unit and the two or more fluid handling unit receiving positions of the expansion housing unit, wherein at least one of the multiple fluid handling units when arranged in a corresponding fluid handling unit receiving position comprises (1) an external section that is external to the main housing unit or the expansion housing unit, and (2) an internal section that is internal to the main housing unit or expansion housing unit, wherein said automated liquid chromatography system is adapted to allow each fluid handing unit to be freely and independently positioned in any one of the fluid handing unit receiving positions of the main housing unit or the expansion housing unit.
18. The automated liquid chromatograph system of claim 17, wherein the external section of the fluid handling units comprises one or more fluid connectors for connecting the fluid handing units arranged in the fluid handling unit receiving positions to a fluid flow path of the automated liquid chromatography system, and the internal section of the fluid handling units comprises an enclosure with one or more air inlet openings.
19. The automated liquid chromatography system of claim 17, wherein the fluid handing units each include a dedicated CPU allowing the fluid handing units to independently perform operations in response to instructions over a system bus.
20. An automated liquid chromatography system comprising: a housing unit comprising an external surface and two or more fluid handling unit receiving positions arranged in a two dimensional array on the external surface of the housing unit; and multiple fluid handling units corresponding in size and shape to two or more fluid handling unit receiving positions, wherein at least one of the multiple fluid handing units when arranged in a corresponding fluid handing unit receiving position comprises (1) an external section that is external to the housing unit, and (2) an internal section that is internal to the housing unit, wherein the external section comprises one or more fluid connectors for connecting with a fluid flow path of the automated liquid chromatography system; wherein the multiple fluid handing units are arranged to be inserted into a fluid handling unit receiving position of the same size and shape from the external surface of the housing unit and are attached into position by a retaining element accessible from the external surface of the housing unit to allow the fluid handling unit to be readily exchanged with other fluid handling units of the same size and shape from the external surface of the housing unit; and wherein said automated liquid chromatography system is adapted to allow each fluid handling unit to be freely and independently positioned in any one of the fluid handing unit receiving positions of the housing unit.
21. The automated liquid chromatography system of claim 20, wherein the internal section comprises an enclosure with one or more air inlet openings.
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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(37) As is disclosed in
(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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