Patent Publication Number: US-2020284767-A1

Title: Valve Unit for a Chromatography Apparatus

Description:
TECHNICAL FIELD 
     The present invention relates to valve unit for a chromatography apparatus. The invention further relates to a chromatography apparatus comprising the valve unit. 
     BACKGROUND 
     Chromatography is a well-known procedure for analyzing and preparing chemical mixtures or chemical samples. The sample may typically be suspended in a fluid, referred to as a buffer composition or resin. The various sample components of the mixture travel at different speeds, causing them to separate. This separation may be used to separate the sample components in a fractionation step where the mobile phase may be directed to different containers, e.g. by an outlet valve of the chromatography apparatus. 
     In some applications, e.g. in the biopharmaceutical field, recent advancements in genetic engineering and cell culture technology have driven expression levels higher than ever, putting a considerable burden on chemical sample down-stream purification, especially the fractionation step. While the introduction of new chromatography buffer compositions significantly improves the efficiency of a process based on a conventional fixed bed chromatography, additional gains can be achieved by operating in a continuous manner. The latter is especially appealing when continuous bioreactors, such as those operated in perfusion mode, are employed. 
     In continuous chromatography, several identical columns are connected in an arrangement that allows columns to be operated in series and/or in parallel, depending on the method requirements. Thus, all columns can be run in principle simultaneously, but slightly shifted in method steps. The procedure may be repeated, such that each column is loaded/packed, eluted, and regenerated several times in the process. Compared to ‘conventional’ chromatography, wherein a single chromatography cycle is based on several consecutive steps, such as loading, wash, elution and regeneration, in continuous chromatography based on multiple identical columns all these steps occur simultaneously but on different columns each. Continuous chromatography operation results in a better utilization of chromatography resin or buffer compositions, reduced processing time and reduced buffer requirements, all of which benefits process economy. Continuous chromatography is sometimes denoted simulated moving bed (SMB) chromatography. 
     In fact, simulated moving bed technology has been utilized for decades in various other fields. For example, U.S. Pat. No. 3,291,726 (Universal Oil Products) described as early as 1966 a continuous simulated counter-current sorption process for the petrochemical industry. 
     As previously mentioned each column may be loaded/packed, eluted, cleaned, and regenerated several times in the process. An essential factor for a reliable continuous chromatography process is the quality of the columns used, and more specifically the similarity or even identity between columns. If the columns are not identical, the theoretical calculations will not be correct, and it will become difficult to design an efficient and robust continuous chromatography process. However, the loading/packing of a column, e.g. with a fluid such as chromatography buffer composition, is very complex in order to obtain repeatable results. Even small differences in the number of plates or other packing properties can have a huge effect on the end result. 
     A problem with conventional solutions is that performing continuous chromatography is a cumbersome, complex and time consuming operation. Often the process must be interrupted to perform reconnection of fluid couplings/tubes, to perform packing of columns or to load a pre-packed column, to perform cleaning operations etc. 
     Thus, there is a need for an improved chromatography apparatus for performing continuous chromatography. 
     OBJECTS OF THE INVENTION 
     An objective of embodiments of the present invention is to provide a solution which mitigates or solves the drawbacks and problems described above. 
     SUMMARY OF THE INVENTION 
     The above and further objectives are achieved by the subject matter described herein. Further advantageous implementation forms of the invention are further defined herein 
     According to a first aspect of the invention, the above mentioned and other objectives are achieved by a valve unit for a chromatography apparatus, the valve unit comprising a fluid inlet configured to receive an input fluid, a fluid outlet configured to provide an output fluid, a first pair of fluid ports configured to be coupled to a first column, a second pair of fluid ports configured to be coupled to a second column, an coupling valve assembly configured to direct fluid between a selection of the fluid inlet, the fluid outlet, the first pair of fluid ports and the second pair of fluid ports in response to one or more control signals, wherein the coupling valve assembly is configured to direct fluid using a selection of membrane valves coupled by fluid channels comprised in a body of the coupling valve assembly. 
     Advantages of the invention according to the first aspect include making continuous chromatography a less cumbersome, a less complex and a less time consuming operation 
     According to a second aspect of the invention, the above mentioned and other objectives are achieved by a membrane valve comprised in the coupling valve assembly according to the first aspect. The membrane valve comprises a body, a membrane arranged in the body and configured to allow flow of fluid between a center port and a side port when positioned in an open position and to block the flow of fluid between the center port and the side port when positioned in a closed position, a piston arranged along a longitudinal axis and coupled to the membrane, a spring arranged along the longitudinal axis and coupled at one end to the piston and at an opposite end to a operable drive, wherein the drive is configured to move the opposite end of the spring along the longitudinal axis in response to a received control signal to obtain said open and closed membrane positions. 
     According to a third aspect of the invention, the above mentioned and other objectives are achieved by a chromatography apparatus comprising the valve unit according to the first aspect. 
     The advantages of the second and third aspect of the invention are at least the same as for the first aspect of the invention. 
     Further applications and advantages of embodiments of the invention will be apparent from the following detailed description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a valve unit for a chromatography apparatus according to one or more embodiments of the present disclosure. 
         FIG. 2  shows a section view of the valve unit according to one or more embodiments of the present disclosure. 
         FIG. 3  shows a section view of one membrane valve comprised in the coupling valve assembly according to one or more embodiments of the present disclosure. 
         FIG. 4  shows a chromatography apparatus according to one or more embodiments of the disclosure. 
         FIG. 5  shows a control unit according to one or more embodiments of the present invention. 
         FIG. 6A-D  schematically shows the coupling valve assembly operating in a single column flow mode according to one or more embodiments of the present invention. 
         FIG. 7A-B  schematically shows the coupling valve assembly operating in a dual-column continuous flow mode according to one or more embodiments of the present invention. 
         FIG. 8A-C  schematically shows the coupling valve assembly  200  operating in a bypass mode according to one or more embodiments of the present invention. 
         FIG. 9  schematically shows the coupling valve assembly  200  operating in a waste mode according to one or more embodiments of the present invention. 
         FIG. 10A-D  schematically shows the coupling valve assembly  200  operating in an unpacking mode according to one or more embodiments of the present invention. 
         FIG. 11A-B  schematically shows the coupling valve assembly  200  operating in an intelligent packing mode according to one or more embodiments of the present invention. 
     
    
    
     A more complete understanding of embodiments of the invention will be afforded to those skilled in the art, as well as a realization of additional advantages thereof, by a consideration of the following detailed description of one or more embodiments. It should be appreciated that like reference numerals are used to identify like elements illustrated in one or more of the figures. 
     DETAILED DESCRIPTION 
     An “or” in this description and the corresponding claims is to be understood as a mathematical OR which covers “and” and “or”, and is not to be understand as an XOR (exclusive OR). The indefinite article “a” in this disclosure and claims is not limited to “one” and can also be understood as “one or more”, i.e., plural. 
     In the present disclosure reference will be made interchangeably to container or reservoir, signifying a receptacle suitable for holding fluid. In the present disclosure reference will be made interchangeably to control system, processor and processing means. 
     In the present disclosure reference will be made interchangeably to a direct shape, a continuous shape or a coherent shape signifying a shape that substantially follows a continuous line, i.e. has no branches or forks between a start point of the line and an end point of the line. 
       FIG. 1  shows a valve unit  100  for a chromatography apparatus  400  according to one or more embodiments of the present disclosure. The chromatography apparatus  400  may be configured for performing continuous chromatography. The valve unit  100  comprises a fluid inlet  110  configured to receive an input fluid. The input fluid may e.g. be a chemical sample suspended in a buffer composition. The valve unit  100  further comprises a fluid outlet  120  configured to provide an output fluid from the valve unit  100 . The provided output fluid may typically be the resulting fluid after passing the received input fluid through one or more columns of the chromatography apparatus  400 . The valve unit  100  further comprises a first pair of fluid ports  130  configured to be coupled to a first column and/or a second pair of fluid ports  140  configured to be coupled to a second column. The valve unit  100  further comprises a coupling valve assembly  200  configured to direct fluid between a selection of the fluid inlet  110 , the fluid outlet  120 , the first pair of fluid ports  130  and the second pair of fluid ports  140  in response to one or more control signals. 
     The valve unit  100  further comprises circuitry or control circuitry, e.g. in the form of a processor and a memory. The memory contains instructions executable by the processor, whereby the valve unit  100  is operative and/or configured to direct fluid based on the one or more control signals. In one example, the circuitry receives a control signal and controls a set of membrane valves comprised in the coupling valve assembly  200  to an open or closed position. 
     The control signal may comprise a single or a plurality of control signals or control signal components indicative of a desired fluid coupling behavior of the coupling valve assembly  200 , i.e. indicative of a desired manner to direct fluid to or from the fluid inlet  110 , the fluid outlet  120 , the first pair of fluid ports  130  and the second pair of fluid ports  140 . The coupling valve assembly  200  is configured to direct fluid using a selection of membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  coupled by fluid channels comprised in a body  201  of the coupling valve assembly  200 . The control signal may comprise a wired or wireless signal capable of comprising information, e.g. a computer bus signal. 
     The membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are configured to allow flow of fluid when positioned in an open position and to block the flow of fluid when positioned in a closed position, as further described in relation to  FIG. 3 . Each fluid channel has a direct, a continuous or a coherent shape that connects two points in a direct, a continuous or a coherent manner to provide a fluid flow or a continuous fluid flow or a coherent fluid flow, thereby avoiding dead/stationary/stagnant legs, e.g. avoiding forks or branches in the fluid channel. 
     In one example, a first fluid channel connects fluid inlet  110  directly to a first membrane valve and a second subsequent fluid channel connects the first membrane valve directly to a second membrane valve in a direct, a continuous or a coherent manner, thereby avoiding dead/stationary/stagnant legs. 
     In one example, the one or more control signals are indicative of a desired position of the membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276 , i.e. an open position or a closed position. 
     The valve unit  100  may further comprise any number of additional pairs of fluid ports for additional columns without deviating from the teaching of the present disclosure. 
     The first pair of fluid ports  130  may typically comprise a first fluid port  131  configured to be coupled to a top part of the first column and a second fluid port  132  configured to be coupled to a bottom part of the first column. The second pair of fluid ports  140  typically comprise a third fluid port  141  configured to be coupled to a top part of the second column and a fourth fluid port  142  configured to be coupled to a bottom part of the second column. 
     The valve unit  100  may in one or more embodiments operate in a single column downward flow mode, further described in relation to  FIG. 6B  and  FIG. 6D . 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a first control signal  1 _DOWN, couple the fluid inlet  110  to the first fluid port  131  and to couple the second fluid port  132  to the fluid outlet  120 . 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a second control signal  2 _DOWN, couple the fluid inlet  110  to the third fluid port  141  and to couple the fourth fluid port  142  to the fluid outlet  120 . 
     The valve unit  100  may in one or more embodiments operate in a single column upward flow mode, further described in relation to  FIG. 6A  and  FIG. 6C . 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a third control signal  1 _UP, couple the fluid inlet  110  to the second fluid port  132  and to couple the first fluid port  131  to the fluid outlet  120  in response to receiving a third control signal  1 _UP. 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a fourth control signal  2 _UP, couple the fluid inlet  110  to the fourth fluid port  142  and to couple the third fluid port  141  to the fluid outlet  120 . 
     The valve unit  100  may in one or more embodiments operate in a dual-column continuous flow mode, further described in relation to  FIG. 7A  and  FIG. 7B . 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a fifth control signal  1 _DOWN- 2 _DOWN, couple the fluid inlet  110  to the first fluid port  131 , couple the second fluid port  132  to the third fluid port  141 , and couple the fourth fluid port  142  to the fluid outlet  120 . 
     In an embodiment, the coupling valve assembly  200  is configured to, in response to a sixth control signal  2 _DOWN- 1 _DOWN, couple the fluid inlet  110  to the third fluid port  141 , couple the fourth fluid port  142  to the first fluid port  131  and to couple the second fluid port  132  to the fluid outlet  120 . 
     The valve unit  100  may in one or more embodiments operate in a bypass mode, further described in relation to  FIG. 8A-C . 
     In an embodiment, the coupling valve assembly ( 200 ) is configured to couple the fluid inlet  110  to the fluid outlet  120  in response to receiving a seventh control signal BY_PASS_ALL, an eighth control signal BY_PASS_TOP or a ninth control signal BY_PASS_BOTTOM. 
     The valve unit  100  may in one or more embodiments operate in a waste mode, further described in relation to  FIG. 9 . 
     In an embodiment, the coupling valve assembly  200  further comprises a waste fluid port  160  and the coupling valve assembly  200  is configured to couple the fluid inlet  110  to the waste fluid port  160  in response to receiving a control signal  1 _IP or  2 _IP. 
     The valve unit  100  may in one or more embodiments operate in a packing or intelligent packing mode, further described in relation to  FIG. 11A-B . 
     In an embodiment, the coupling valve assembly  200  further comprises a intelligent packing fluid port or packing fluid port  150  and the coupling valve assembly  200  is configured to couple the fluid inlet  110  to intelligent packing fluid port or packing fluid port  150  in response to receiving a control signal  1 _IP or  2 _IP. 
     The valve unit  100  may in one or more embodiments comprise fluid channels formed in a direct shape. 
     In an embodiment, the fluid channels comprised in the body  201  of the coupling valve assembly  200  are formed in a direct shape. The fluid channels are formed in a direct shape in the sense that each individual fluid channel is formed with one end terminating at a start point and an opposite end terminating at an end point. Each individual fluid channel may further be shaped with a substantially constant area of cross sections along the fluid channel. The start point and the end point comprises at least one of the fluid inlet  110 , the fluid outlet  120 , the first fluid port  131 , the second fluid port  132 , the third fluid port  141 , the fourth fluid port  142 , a center port  306  and an side port  307 . The center port  306  and the side port  307  are typically comprised in of one of the membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276 . Thereby dead/stationary/stagnant legs, where fluid remains stationary when fluid flows in the fluid channel, are avoided. Fluid channels are further described in relation to  FIG. 2 . 
     The valve unit  100  may in one or more embodiments be configured to provide one or more control or sensor signals indicative of fluid pressure at the fluid inlet  110  and/or the fluid outlet  120 . 
     In an embodiment, the coupling valve assembly  200  further comprises a first pressure sensor  281  coupled to the fluid inlet  110  and configured for measuring a first pressure of the received fluid and a second pressure sensor  282  coupled to the fluid outlet  120  and configured for measuring a second pressure of the provided fluid. 
       FIG. 2  shows a section view of the valve unit  100  according to one or more embodiments of the present disclosure. As further described in relation to  FIG. 1 , the valve unit  100  comprises the fluid inlet  110 , the fluid outlet  120 , the first fluid port  131  coupled to a side port of a first membrane valve  231 , the second fluid port  132  coupled to a side port of a second membrane valve  232 , the third fluid port  141  coupled to a side port of a third membrane valve  241  and the fourth fluid port  142  coupled to a side port of a fourth membrane valve  242 . The valve unit  100  further comprises a fifth membrane valve  271 , a sixth membrane valve  272 , a seventh membrane valve  273 , an eight membrane valve  274 , a ninth membrane valve  275  and a tenth membrane valve  276 . 
     The valve unit  100  may optionally further comprise an eleventh membrane valve  250  and a twelfth membrane valve  260 . 
     A first fluid channel  291 , formed in a direct shape, couples the fluid inlet  110  to the seventh membrane valve  273 , e.g. to a center port of the seventh membrane valve  273 . A second fluid channel  292 , formed in a direct shape, couples the seventh membrane valve  273 , e.g. the side port, to the tenth membrane valve  276 , e.g. to the center port. A third fluid channel  293 , formed in a direct shape, couples the tenth membrane valve  276 , e.g. the side port, to the sixth membrane valve  272 , e.g. to the center port. A fourth fluid channel  294 , formed in a direct shape, couples the sixth membrane valve  272 , e.g. the side port, to the fluid outlet  120 . A fifth fluid channel  295 , formed in a direct shape, couples the eight membrane valve  274 , e.g. the side port, to the ninth membrane valve  275 , e.g. to the center port. The center port of the eight membrane valve  274  is further coupled to the first fluid channel  291 . A sixth fluid channel  296 , formed in a direct shape, couples the ninth membrane valve  275 , e.g. the side port, to the fifth membrane valve  271 , e.g. to the center port. 
     The first fluid channel  291  may also be coupled to the eleventh membrane valve  250 , e.g. to the center port. The first fluid channel  291  may also be coupled to the twelfth membrane valve  260 , e.g. to the center port. 
     In an optional embodiment, the coupling valve assembly  200  further comprises a first pressure sensor  281  coupled to the fluid inlet  110  and configured for measuring a first pressure of the input fluid. The pressure sensor  281  may be coupled to the fluid inlet  110  by the first fluid channel  291 , e.g. in-between the fluid inlet  110  and the eleventh membrane valve  250 . In a further optional embodiment, the coupling valve assembly  200  further comprises a second pressure sensor  282  coupled to the fluid outlet  120  and configured for measuring a second pressure of the output fluid. 
       FIG. 3  shows a section view of one membrane valve  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  comprised in the coupling valve assembly  200  according to one or more embodiments of the present disclosure shown mid way between it&#39;s open and closed positions. In practice the valve will be closed as a default position, and opened when needed, according to the technique described below. 
     The membrane valve comprises the body  201  of the coupling valve assembly  200 . The membrane valve further comprises a membrane  310  arranged in the body  201  and configured to allow flow of fluid between a center port  306  and a side port  307  when positioned in an open position and to block the flow of fluid between the center port  306  and the side port  307  when positioned in a closed position. 
     The membrane valve further comprises a piston  304  arranged along a longitudinal axis  315  and coupled to the membrane  310 . The membrane valve further comprises a spring  314  arranged along the longitudinal axis  315  and at one end in contact with a piston  304 , the spring being urgeable at an opposite end by a drive  301 . The drive  301  is configured to move the opposite end of the spring  314  along the longitudinal axis  315  in response to a received control signal to obtain said open and closed membrane positions. 
     The membrane valve  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  may further comprise a valve front  308 , and a valve rear  305 , in this case, both being part of the valve body  201 . The valve membrane  310  is held firmly between the front  308  and rear  305  of the valve body  201 . 
     In one example of operating the membrane valve  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276 , a closing procedure from the “open” position is started. Circuitry, such as a microprocessor, comprised in the valve unit  100  gets a control signal from a control unit  410  in the chromatography apparatus indicative of a desire to close the valve. The circuitry causes the drive  301 , e.g. a stepper motor, to move the spring housing  313  forward, pushing the spring  314  that pushes the piston  304 , which presses the membrane  310  into the seat  309 , thereby closing off the center port  306  from the side port  307 . The center port  306  is normally the port for fluid in-flow, but it can also be the port for out-flow. When the membrane  310  reaches the seat  309 , the piston  304  is prevented from moving further, but the drive  301  keeps pushing, thereby compressing the spring  314  which gives an increased force on the membrane  310  fro closing the valve. When the spring housing  313  has reached a certain position, a position flag close  302  is detected by a position sensor close  303 . The stepper motor can then stop, or, if necessary, move a known amount of extra steps to increase the force applied to the membrane  310  even further. 
     In embodiments, some of the membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  valves comprised in the coupling valve assembly  200  have high demands on short motion time and some have lower demands on speed but higher demands on closing force. The membrane valves with high demands on short motion time, may stop at the flag. Membrane valves with lower demands on speed but higher demands on closing force, may move an extra fixed distance. The behavior of valves with regards to the flag may be fully configurable from the control unit software, i.e. the hardware is exactly the same. E. g. in the coupling valve assembly  200  herein we can have both types of behavior of valves at different positions within the coupling valve assembly  200 . 
     In one example of operating the membrane valve  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276 , an opening procedure from the “closed” position is started. The drive  301  moves on command or in response to control signals from the control unit  410  in the chromatography apparatus  400  indicative of a desire to open the valve. The drive  301  pulls on the spring housing  313 . This releases the spring force until the back portion of the piston  304  is engaged with the spring housing, and the drive  301  starts pulling at the piston  304 . The piston pulls the membrane which in turn is pulled out to the open position. When the position flag open  312  is detected by the piston sensor open  311 , the drive  301  stops. The drive  301  does not move any extra steps when moving to the open position, but it is of course possible if needed. 
       FIG. 4  shows a chromatography apparatus  400  according to one or more embodiments of the disclosure. The chromatography apparatus  400  may typically comprise at least one inlet  455 . The inlet may optionally be coupled to a reservoir  451  configured to hold a fluid. The inlet  455  may e.g. be implemented as tubular elements such as a tube or hose. The chromatography apparatus  400  may further comprise the valve unit  100 , further described in relation to  FIG. 1 . The valve unit  100  may be coupled to the reservoir  451  by the inlet  455  coupled to the fluid inlet  110 . The valve unit  100  may be configured to be coupled to the first column  441  by the first pair of fluid ports  130  and/or configured to be coupled to the second column  442  by the second pair of fluid ports  140 . The first column  441  and/or the second column  442  may be comprised in the chromatography apparatus  400  or arranged external to the chromatography apparatus  400 . 
     The chromatography apparatus  400  may further comprise an intelligent packing fluid port or packing fluid port  150  configured to be coupled to a packing port of the first column  441  or the second column  442 . The chromatography apparatus  400  may further comprise a waste fluid port  160  configured to be coupled to a waste reservoir or drain. 
     The chromatography apparatus  400  may further comprise a control unit  410  which comprises circuitry, e.g. a processor and a memory. The memory may contain instructions executable by the processor, whereby said chromatography apparatus is operative to perform any of the steps or methods described herein. The control unit  410  is further described in relation to  FIG. 5 . 
     The chromatography apparatus  400  may optionally comprise a splitter  470  coupled to the fluid outlet  120  of the valve unit  100  and coupled to a selection of any of a pH sensor  431 , a conductivity sensor  432  and an outlet valve  420 . The splitter  470  may be configured to direct fluid received from the injection unit  480  to any of any of the pH sensor  431 , the conductivity sensor  432  and the outlet valve  420 . Optionally the splitter  470  may be communicatively coupled to the control unit and perform coupling of fluid in in response to a control signal from the control unit  410 . 
     The pH sensor  431  may be communicatively coupled to the control unit  410  and configured for measuring the pH of the fluid provided by the splitter  470 . The chromatography apparatus  400  may further comprise a conductivity sensor  432  communicatively coupled to the control unit  410  and configured for measuring the conductivity of the fluid provided by the splitter  470 . The pH sensor  431  and/or the conductivity sensor  432  may further be configured to provide the measured pH and measured conductivity as control signals comprising measurement data to the control unit  410 . 
     The chromatography apparatus  400  may further comprise an outlet valve  420  coupled to the splitter  470 . The outlet valve  420  may have one or more outlets or outlet ports  421 - 423  and is configured to provide the fluid provided by the splitter  470  to the one or more outlets  421 - 423  in response to a control signal, e.g. received from the control unit  410 . 
       FIG. 5  shows the control unit  410  according to one or more embodiments of the present invention. The control unit  410  may be in the form of e.g. an Electronic Control Unit, a server, an on-board computer, a stationary computing device, a laptop computer, a tablet computer, a handheld computer, a wrist-worn computer, a smart watch, a smartphone or a smart TV. The control unit  410  may comprise a processor  412  communicatively coupled to a transceiver  404  configured for wired or wireless communication. The control unit  410  may further comprise at least one optional antenna (not shown in figure). The antenna may be coupled to the transceiver  404  and is configured to transmit and/or emit and/or receive wired or wireless signals in a communication network, such as WiFi, Bluetooth, 3G, 4G, 5G etc. In one example, the processor  412  may be any of a selection of processing circuitry and/or a central processing unit and/or processor modules and/or multiple processors configured to cooperate with each-other. Further, the control unit  410  may further comprise a memory  415 . The memory  415  may e.g. comprise a selection of a hard RAM, disk drive, a floppy disk drive, a flash drive or other removable or fixed media drive or any other suitable memory known in the art. The memory  415  may contain instructions executable by the processor to perform any of the steps or methods described herein. The processor  412  may be communicatively coupled to a selection of any of the transceiver  404 , the memory  415  the pH sensor  431 , the conductivity sensor  432 , the outlet valve  420  and the splitter  470 . The control unit  410  may be configured to send/receive control signals directly to any of the above mentioned units or to external nodes or to send/receive control signals via the wired and/or wireless communications network. 
     The wired/wireless transceiver  404  and/or a wired/wireless communications network adapter may be configured to send and/or receive data values or parameters as a signal to or from the processor  412  to or from other external nodes. E.g. measured pH or conductivity values. 
     In an embodiment, the transceiver  404  communicates directly to external nodes or via the wireless communications network. 
     In one or more embodiments the control unit  410  may further comprise an input device  417 , configured to receive input or indications from a user and send a user input signal indicative of the user input or indications to the processing means  412 . 
     In one or more embodiments the control unit  410  may further comprise a display  418  configured to receive a display signal indicative of rendered objects, such as text or graphical user input objects, from the processing means  412  and to display the received signal as objects, such as text or graphical user input objects. 
     In one embodiment the display  418  is integrated with the user input device  417  and is configured to receive a display signal indicative of rendered objects, such as text or graphical user input objects, from the processing means  412  and to display the received signal as objects, such as text or graphical user input objects, and/or configured to receive input or indications from a user and send a user-input signal indicative of the user input or indications to the processing means  412 . 
     In a further embodiment, the control unit  410  may further comprise and/or be coupled to one or more additional sensors (not shown in the figure) configured to receive and/or obtain and/or measure physical properties pertaining to the chromatography apparatus  400  and send one or more sensor signals indicative of the physical properties to the processing means  412 . 
     In one or more embodiments, the processing means  412  is further communicatively coupled to the input device  417  and/or the display  418  and/or the additional sensors. 
       FIG. 6A  schematically shows the coupling valve assembly  200  operating in a single column upward flow mode for the first column  441  according to one or more embodiments of the present invention.  FIG. 6A  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  1 _UP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the tenth membrane valve  276 , the second membrane valve  232 , the first membrane valve  231 , the ninth membrane valve  275  and the fifth membrane valve  271  are then controlled to the open position. The first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 6B  schematically shows the coupling valve assembly  200  operating in a single column downward flow mode for the first column  441  according to one or more embodiments of the present invention.  FIG. 6B  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  1 _DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , the first membrane valve  231 , the second membrane valve  232  and the sixth membrane valve  272  are then controlled to the open position. The first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 6C  schematically shows the coupling valve assembly  200  operating in a single column upward flow mode for the second column  442  according to one or more embodiments of the present invention.  FIG. 6C  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  2 _UP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , ninth membrane valve  275 , the fourth membrane valve  242 , the third membrane valve  241  and the tenth membrane valve  276  are then controlled to the open position. The second column  442  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 6D  schematically shows the coupling valve assembly  200  operating in a single column downward flow mode for the second column  442  according to one or more embodiments of the present invention.  FIG. 6D  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  2 _DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the third membrane valve  241 , the fourth membrane valve  242  and the fifth membrane valve  271  are then controlled to the open position. The first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 7A  schematically shows the coupling valve assembly  200  operating in a dual-column continuous flow mode from the second column  442  to the first column  441  according to one or more embodiments of the present invention.  FIG. 7A  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  2 _DOWN- 1 _DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the third membrane valve  241 , the fourth membrane valve  242 , the ninth membrane valve  275 , the first membrane valve  231 , the second membrane valve  232  and the sixth membrane valve  272  are then controlled to the open position. The second column  442  and/or the first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 7B  schematically shows the coupling valve assembly  200  operating in a dual-column continuous flow mode from the first column  441  to the second column  442  according to one or more embodiments of the present invention.  FIG. 7B  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  1 _DOWN- 2 _DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , the first membrane valve  231 , the second membrane valve  232 , the tenth membrane valve  276 , the third membrane valve  241 , the fourth membrane valve  242  and the fifth membrane valve  271  are then controlled to the open position. The first column  441  and/or the second column  442  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 8A  schematically shows the coupling valve assembly  200  operating in a top bypass mode according to one or more embodiments of the present invention.  FIG. 8A  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal, BY_PASS_TOP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the tenth membrane valve  276  and the sixth membrane valve  272  are then controlled to the open position. The fluid channels providing the top part of the columns with fluid are then filled, rinsed or cleaned, e.g. to prepare the fluid channels for an upcoming chromatography run. 
       FIG. 8B  schematically shows the coupling valve assembly  200  operating in a bottom bypass mode according to one or more embodiments of the present invention.  FIG. 8B  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal, BY_PASS_BOTTOM, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , the ninth membrane valve  275  and the fifth membrane valve  271  are then controlled to the open position. The fluid channels providing the bottom part of the columns with fluid are then filled, rinsed or cleaned, e.g. to prepare the fluid channels for an upcoming chromatography run. 
       FIG. 8C  schematically shows the coupling valve assembly  200  operating in an all bypass mode according to one or more embodiments of the present invention.  FIG. 8C  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal, BY_PASS_ALL, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the tenth membrane valve  276  and the sixth membrane valve  272 , the eight membrane valve  274 , the ninth membrane valve  275  and the fifth membrane valve  271  are then controlled to the open position. The fluid channels providing the top and bottom parts of the columns with fluid are then filled, rinsed or cleaned, e.g. to prepare the fluid channels for an upcoming chromatography run. 
       FIG. 9  schematically shows the coupling valve assembly  200  operating in a waste mode according to one or more embodiments of the present invention.  FIG. 9  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal, WASTE, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The twelfth membrane valve  260  is then controlled to the open position. The fluid is then typically provided to a waste container. 
       FIG. 10A  schematically shows the coupling valve assembly  200  first column downward unpacking mode according to one or more embodiments of the present invention.  FIG. 10A  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  1 _UNPACK_DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274  and the first membrane valve  231  are then controlled to the open position. 
       FIG. 10B  schematically shows the coupling valve assembly  200  first column upward unpacking mode according to one or more embodiments of the present invention.  FIG. 10B  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  1 _UNPACK_UP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The seventh membrane valve  273 , the tenth membrane valve  276  and the second membrane valve  232  are then controlled to the open position. 
       FIG. 10C  schematically shows the coupling valve assembly  200  second column downward unpacking mode according to one or more embodiments of the present invention.  FIG. 10C  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  2 _UNPACK_DOWN, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , the ninth membrane valve  275  and the fourth membrane valve  242  are then controlled to the open position. 
       FIG. 10D  schematically shows the coupling valve assembly  200  second column upward unpacking mode according to one or more embodiments of the present invention.  FIG. 10D  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. A control signal,  2 _UNPACK_UP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eight membrane valve  274 , the ninth membrane valve  275  and the fourth membrane valve  242  are then controlled to the open position. 
       FIG. 11A  schematically shows the coupling valve assembly  200  operating in an intelligent packing flow mode or packing flow mode for the first column  441  according to one or more embodiments of the present invention.  FIG. 11A  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. The eleventh membrane valve  250  is coupled to the first column. A control signal,  1 _IP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eleventh membrane valve  250 , the second membrane valve  232  and the sixth membrane valve  272  are then controlled to the open position. The first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
       FIG. 11B  schematically shows the coupling valve assembly  200  operating in an intelligent packing flow mode or packing flow mode for the second column  442  according to one or more embodiments of the present invention.  FIG. 11B  further shows the various membrane valves and fluid channels comprised by the coupling valve assembly  200 , further described in relation to  FIG. 2 . 
     In one example, all membrane valves  231 ,  232 ,  241 ,  242 ,  250 ,  260 ,  271 - 276  are initially in the closed position. The eleventh membrane valve  250  is coupled to the second column. A control signal,  2 _IP, is then received, e.g. by circuitry comprised in the coupling valve assembly  200 , and a set of the membrane valves are then controlled to the open position. The eleventh membrane valve  250 , the fourth membrane valve  242  and the fifth membrane valve  271  are then controlled to the open position. The first column  441  may then be packed or filled with fluid, e.g. to prepare for an upcoming chromatography run. 
     In embodiments, the communications network communicate using wired or wireless communication techniques that may include at least one of a Local Area Network (LAN), Metropolitan Area Network (MAN), Global System for Mobile Network (GSM), Enhanced Data GSM Environment (EDGE), Universal Mobile Telecommunications System, Long term evolution, High Speed Downlink Packet Access (HSDPA), Wideband Code Division Multiple Access (W-CDMA), Code Division Multiple Access (CDMA), Time Division Multiple Access (TDMA), Bluetooth®, Zigbee®, Wi-Fi, Voice over Internet Protocol (VoIP), LTE Advanced, IEEE802.16m, WirelessMAN-Advanced, Evolved High-Speed Packet Access (HSPA+), 3GPP Long Term Evolution (LTE), Mobile WiMAX (IEEE 802.16e), Ultra Mobile Broadband (UMB) (formerly Evolution-Data Optimized (EV-DO) Rev. C), Fast Low-latency Access with Seamless Handoff Orthogonal Frequency Division Multiplexing (Flash-OFDM), High Capacity Spatial Division Multiple Access (iBurst®) and Mobile Broadband Wireless Access (MBWA) (IEEE 802.20) systems, High Performance Radio Metropolitan Area Network (HIPERMAN), Beam-Division Multiple Access (BDMA), World Interoperability for Microwave Access (WiMAX) and ultrasonic communication, etc., but is not limited thereto. 
     Moreover, it is realized by the skilled person that the control unit  410  may comprise the necessary communication capabilities in the form of e.g., functions, means, units, elements, etc., for performing the present solution. Examples of other such means, units, elements and functions are: processors, memory, buffers, control logic, encoders, decoders, rate matchers, de-rate matchers, mapping units, multipliers, decision units, selecting units, switches, interleavers, de-interleavers, modulators, demodulators, inputs, outputs, antennas, amplifiers, receiver units, transmitter units, DSPs, MSDs, TCM encoder, TCM decoder, power supply units, power feeders, communication interfaces, communication protocols, etc. which are suitably arranged together for performing the present solution. 
     Especially, the processor and/or processing means of the present disclosure may comprise one or more instances of processing circuitry, processor modules and multiple processors configured to cooperate with each-other, Central Processing Unit (CPU), a processing unit, a processing circuit, a processor, an Application Specific Integrated Circuit (ASIC), a microprocessor, a Field-Programmable Gate Array (FPGA) or other processing logic that may interpret and execute instructions. The expression “processor” and/or “processing means” may thus represent a processing circuitry comprising a plurality of processing circuits, such as, e.g., any, some or all of the ones mentioned above. The processing means may further perform data processing functions for inputting, outputting, and processing of data comprising data buffering and device control functions, such as call processing control, user interface control, or the like. 
     Finally, it should be understood that the invention is not limited to the embodiments described above, but also relates to and incorporates all embodiments within the scope of the appended independent claims.