Valve unit for chromatography apparatus

Abstract

The invention relates to a valve unit for a chromatography apparatus. The present invention provides 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 the first column; a second pair of fluid ports configured to be coupled to a second column; a fill fluid port configured to be coupled to a fill port of the first column or the second column; wherein the fluid inlet, the fluid outlet, the first pair of fluid ports, the second pair of fluid ports, and the fill fluid port are arranged to be integrated in the valve unit.

Description

This application is a divisional application of the invention patent application with national application number 201880075460.7, the application date of which is September 21, 2018, and the name of the invention is “Valve unit for chromatographic equipment”. Technical Field

[0001] The present invention relates to a valve unit for a chromatography device. The present invention also relates to a chromatography device comprising the valve unit. Background Art

[0002] Chromatography is a well-known procedure for analyzing and preparing chemical mixtures or chemical samples. The sample can usually be suspended in a fluid, called a buffer composition or resin. The various sample components of the mixture travel at different speeds, thereby prompting them to be separated. This separation can be used to separate the sample components in a fractionation step, in which the mobile phase can be directed to different containers, such as by an outlet valve of a chromatographic device.

[0003] In some applications, such as in the field of biopharmaceuticals, recent developments in genetic engineering and cell culture technology have driven expression levels higher than before, thereby adding a considerable burden to the downstream purification of chemical samples, especially the fractionation steps. Although the introduction of new chromatography buffer compositions has greatly improved the efficiency of processes based on conventional fixed bed chromatography, additional gains can be achieved by operating in a continuous manner. The latter is particularly attractive when using continuous bioreactors, such as those operating in perfusion mode.

[0004] In continuous chromatography, several identical posts are connected using an arrangement that allows posts to be operated serially and / or in parallel according to method requirements. Therefore, all posts can be operated simultaneously in principle, but slightly changed in method steps. The procedure can be repeated so that each post is loaded / filled, eluted and regenerated several times in the process. Compared with the 'conventional' chromatography in which a single chromatographic cycle is based on several continuous steps (such as loading, cleaning, eluting and regeneration), in the continuous chromatography based on multiple identical posts, all these steps occur simultaneously but each on different posts. Continuous chromatographic operation results in reduced processing time, reduced buffering requirements and better utilization of chromatographic resins or buffer compositions, which are all beneficial to process economy. Continuous chromatography sometimes refers to simulated moving bed (SMB) chromatography.

[0005] In fact, simulated moving bed technology has been used for decades in various other fields. For example, U.S. Pat. No. 3,291,726 (General Petroleum Products) described a continuous simulated countercurrent adsorption process for the petrochemical industry as early as 1966.

[0006] As previously mentioned, each post can be loaded / filled, eluted, cleaned and regenerated several times in the process. The basic factor for reliable continuous chromatography process is the quality of the post used, and more specifically the similarity or even identity between the posts. If the posts are not identical, then theoretical calculations will not be correct, and it will be difficult to design efficient and robust continuous chromatography process. However, in order to obtain repeatable results, the loading / filling of the post (e.g., using a fluid such as a chromatography buffer composition) is very complicated. Even small differences in the number of plates or other filling properties may have a great impact on the final result.

[0007] The problem with conventional technical solutions is that performing continuous chromatography is a tedious, complex and time-consuming operation. The process must usually be interrupted to perform reconnection of fluidic couplers / tubings, perform column filling or loading of pre-packed columns, perform cleaning operations, etc.

[0008] Therefore, there is a need for improved chromatography apparatus for performing continuous chromatography.

[0009] Invention Objectives It is an object of embodiments of the present invention to provide a solution which mitigates or solves the disadvantages and problems described above. Summary of the invention

[0010] The above and further objects are achieved by the subject matter described herein.Further advantageous implementation forms of the invention are further defined herein.

[0011] According to a first aspect of the present invention, the above-mentioned and other objects are achieved by a valve unit for a chromatographic device, which valve unit includes 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, and a coupling valve assembly configured to guide fluid between selections 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 guide fluid using selection of a diaphragm valve coupled through a fluid channel included in the body of the coupling valve assembly.

[0012] Advantages of the present invention according to the first aspect include making continuous chromatography a less cumbersome, less complicated and less time consuming operation.

[0013] According to a second aspect of the present invention, the above-mentioned and other objects are achieved by a diaphragm valve included in a coupling valve assembly according to the first aspect. The diaphragm valve comprises: a body; a diaphragm arranged in the body and configured to allow fluid to flow between a central port and a side port when placed in an open position and to prevent fluid from flowing between the central port and the side port when placed in a closed position; a piston arranged along a longitudinal axis and coupled to the diaphragm; a spring arranged along the longitudinal axis and coupled to the piston at one end and to an operable driver at the opposite end, wherein the driver is configured to move the opposite end of the spring along the longitudinal axis in response to a received control signal so as to obtain the open diaphragm position and the closed diaphragm position.

[0014] According to a third aspect of the present invention, the above mentioned and other objects are achieved by a chromatography device comprising a valve unit according to the first aspect.

[0015] The advantages of the second and third aspects of the invention are at least the same as those described for the first aspect of the invention.

[0016] Further applications and advantages of embodiments of the present invention will be apparent from the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 A valve unit for a chromatography device according to one or more embodiments of the present disclosure is shown.

[0018] Figure 2 A cross-sectional view of a valve unit for use in accordance with one or more embodiments of the present disclosure is shown.

[0019] Figure 3 A cross-sectional view of a diaphragm valve included in a coupling valve assembly according to one or more embodiments of the present disclosure is shown.

[0020] Figure 4 A chromatography apparatus according to one or more embodiments of the present disclosure is shown.

[0021] Figure 5 A control unit according to one or more embodiments of the present invention is shown.

[0022] Fig. 6A -D schematically illustrates a coupled valve assembly operating in a single column flow mode according to one or more embodiments of the present invention.

[0023] Fig. 7A -B schematically illustrates a coupled valve assembly operating in a dual column continuous flow mode according to one or more embodiments of the present invention.

[0024] Fig. 8A-C schematically illustrates a coupling valve assembly 200 operating in a bypass mode according to one or more embodiments of the present invention.

[0025] Fig. 9 A coupling valve assembly 200 is schematically illustrated operating in a waste mode in accordance with one or more embodiments of the present invention.

[0026] Fig. 10A -D schematically illustrates a coupling valve assembly 200 operating in an unpacking mode according to one or more embodiments of the present invention.

[0027] Fig.11A -B schematically illustrates a coupling valve assembly 200 operating in a smart fill mode according to one or more embodiments of the present invention.

[0028] A more complete understanding of embodiments of the present invention, as well as a realization of additional advantages thereof, will be provided to those skilled in the art by considering 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

[0029] The "or" in this description and the corresponding claims is to be understood as a mathematical OR, which encompasses "and" and "or", and is not to be understood as 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.

[0030] In this disclosure, reference will be made interchangeably to a container or reservoir, which refers to a receptacle suitable for holding a fluid.In this disclosure, reference will be made interchangeably to a control system, a processor, and a processing component.

[0031] In this disclosure, reference will be made interchangeably to direct shapes, continuous shapes, or connected shapes representing shapes that substantially follow one continuous line (ie, without branches or forks between the start point of the line and the end point of the line).

[0032] Figure 1A valve unit 100 for a chromatography device 400 according to one or more embodiments of the present disclosure is shown. The chromatography device 400 can be configured to perform continuous chromatography. The valve unit 100 includes a fluid inlet 110, which is configured to receive an input fluid. The input fluid can be, for example, a chemical sample suspended in a buffer composition. The valve unit 100 also includes a fluid outlet 120, which is configured to provide an output fluid from the valve unit 100. The output fluid provided can generally be a fluid obtained after passing the received input fluid through one or more columns of the chromatography device 400. The valve unit 100 also includes 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 also includes a coupling valve assembly 200, which is configured to direct fluid between the 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.

[0033] The valve unit 100 also includes a circuit system or control circuit system, for example in the form of a processor and a memory. The memory contains instructions executable by the processor, whereby the valve unit 100 operates and / or is configured to direct the fluid based on one or more control signals. In one example, the circuit system receives the control signal and controls a set of diaphragm valves included in the coupling valve assembly 200 to an open or closed position.

[0034] The control signal may include a single or multiple control signals or control signal components that indicate a desired fluid coupling behavior of the coupling valve assembly 200, i.e., a desired manner for directing fluid to and 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 diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 coupled via fluid passages included in the body 201 of the coupling valve assembly 200. The control signal may include a wired or wireless signal that can include information, such as a computer bus signal.

[0035] The diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are configured to allow fluid flow when placed in an open position and to prevent fluid flow when placed in a closed position, as described with respect to Figure 3 Each fluid channel has a direct, continuous or coherent shape that connects two points in a direct, continuous or coherent manner to provide a fluid flow or a continuous fluid flow or a coherent fluid flow, thereby avoiding dead / stationary / stagnant legs, such as avoiding bifurcations or branches in the fluid channel.

[0036] In one example, a first fluid channel connects the fluid inlet 110 directly to a first diaphragm valve, and a second subsequent fluid channel connects the first diaphragm valve directly to a second diaphragm valve in a direct, continuous or coherent manner, thereby avoiding no-flow / stationary / stagnant segments.

[0037] In one example, the one or more control signals indicate a desired position of the diaphragm valves 231 , 232 , 241 , 242 , 250 , 260 , 271 - 276 , ie, an open position or a closed position.

[0038] The valve unit 100 may also include any number of additional conduit ports for additional columns without departing from the teachings of the present disclosure.

[0039] The first pair of fluid ports 130 may generally include: a first fluid port 131 configured to couple to a top portion of a first column; and a second fluid port 132 configured to couple to a bottom portion of the first column. The second pair of fluid ports 140 may generally include: a third fluid port 141 configured to couple to a top portion of a second column; and a fourth fluid port 142 configured to couple to a bottom portion of the second column.

[0040] The valve unit 100 can be operated in a single column downflow mode in one or more embodiments, which further relates to Figure 6B and Fig.6D describe.

[0041] In an embodiment, the coupling valve assembly 200 is configured to 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 response to a first control signal 1_DOWN.

[0042] In an embodiment, the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the third fluid port 141 and to couple the fourth fluid port 142 to the fluid outlet 120 in response to the second control signal 2_DOWN.

[0043] The valve unit 100 can be operated in a single column upward flow mode in one or more embodiments, which further relates to Fig. 6A and Figure 6C describe.

[0044] In an embodiment, the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the second fluid port 132 in response to the third control signal 1_UP and to couple the first fluid port 131 to the fluid outlet 120 in response to receiving the third control signal 1_UP.

[0045] In an embodiment, the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the fourth fluid port 142 and to couple the third fluid port 141 to the fluid outlet 120 in response to the fourth control signal 2_UP.

[0046] The valve unit 100 can be operated in a dual column continuous flow mode in one or more embodiments, which further relates to Fig. 7A and Figure 7B describe.

[0047] In an embodiment, the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the first fluid port 131 , the second fluid port 132 to the third fluid port 141 , and the fourth fluid port 142 to the fluid outlet 120 in response to a fifth control signal 1_DOWN- 2_DOWN.

[0048] In an embodiment, the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the third fluid port 141 , the fourth fluid port 142 to the first fluid port 131 , and the second fluid port 132 to the fluid outlet 120 in response to the sixth control signal 2_DOWN- 1_DOWN.

[0049] The valve unit 100 can be operated in a bypass mode in one or more embodiments, which further relates to Fig. 8A -C description.

[0050] 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 the seventh control signal BY_PASS_ALL, the eighth control signal BY_PASS_TOP, or the ninth control signal BY_PASS_BOTTOM.

[0051] The valve unit 100 can be operated in a waste mode in one or more embodiments, which further relates to Fig. 9 describe.

[0052] In an embodiment, the coupling valve assembly 200 further includes 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 the control signal WASTE.

[0053] The valve unit 100 can be operated in a fill or smart fill mode in one or more embodiments, which further relates to Fig.11A -B Description.

[0054] In an embodiment, the coupling valve assembly 200 further includes a smart fill fluid port or fill fluid port 150 , and the coupling valve assembly 200 is configured to couple the fluid inlet 110 to the smart fill fluid port or fill fluid port 150 in response to receiving the control signal 1_IP or 2_IP.

[0055] The valve unit 100 may include a fluid channel formed in a straight shape in one or more embodiments.

[0056] In an embodiment, the fluid channel included in the body 201 of the coupling valve assembly 200 is formed in a direct shape. The fluid channel is formed in a direct shape in the sense that each individual fluid channel is formed with one end terminating at a starting point and the opposite end terminating at an end point. Each individual fluid channel may also be shaped to have a substantially constant cross-sectional area along the fluid channel. The starting point and the end point include at least one of the following: a fluid inlet 110, a fluid outlet 120, a first fluid port 131, a second fluid port 132, a third fluid port 141, a fourth fluid port 142, a center port 306, and a side port 307. The center port 306 and the side port 307 are typically included in one of the diaphragm valves 231, 232, 241, 242, 250, 260, 271-276. Thereby, a non-flowing / stationary / stagnant section is avoided, and the fluid remains stationary in the non-flowing / stationary / stagnant section when the fluid flows in the fluid channel. About Figure 2 The fluid channel is further described.

[0057] The valve unit 100 , in one or more embodiments, may 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 .

[0058] In an embodiment, the coupling valve assembly 200 further includes: a first pressure sensor 281 coupled to the fluid inlet 110 and configured to measure a first pressure of the received fluid; and a second pressure sensor 282 coupled to the fluid outlet 120 and configured to measure a second pressure of the provided fluid.

[0059] Figure 2 1 shows a cross-sectional view of a valve unit 100 according to one or more embodiments of the present disclosure. Figure 1As further described, the valve unit 100 includes a fluid inlet 110, a fluid outlet 120, a first fluid port 131 coupled to a side port of a first diaphragm valve 231, a second fluid port 132 coupled to a side port of a second diaphragm valve 232, a third fluid port 141 coupled to a side port of a third diaphragm valve 241, and a fourth fluid port 142 coupled to a side port of a fourth diaphragm valve 242. The valve unit 100 also includes a fifth diaphragm valve 271, a sixth diaphragm valve 272, a seventh diaphragm valve 273, an eighth diaphragm valve 274, a ninth diaphragm valve 275, and a tenth diaphragm valve 276.

[0060] The valve unit 100 may optionally further include an eleventh diaphragm valve 250 and a twelfth diaphragm valve 260 .

[0061] The first fluid channel 291 formed in a direct shape couples the fluid inlet 110 to the seventh diaphragm valve 273, for example, to the central port of the seventh diaphragm valve 273. The second fluid channel 292 formed in a direct shape couples the second diaphragm valve 232 (for example, a side port) to the tenth diaphragm valve 276, for example, to the central port. The third fluid channel 293 formed in a direct shape couples the second diaphragm valve 232 (for example, a side port) to the sixth diaphragm valve 272, for example, to the central port. The fourth fluid channel 294 formed in a direct shape couples the sixth diaphragm valve 272 (for example, a side port) to the fluid outlet 120. The fifth fluid channel 295 formed in a direct shape couples the eighth diaphragm valve 274 (for example, a side port) to the ninth diaphragm valve 275, for example, to the central port. The central port of the eighth diaphragm valve 274 is also coupled to the first fluid channel 291. The sixth fluid passage 296 formed in a straight shape couples the ninth diaphragm valve 275 (eg, a side port) to the fifth diaphragm valve 271 , for example, to the center port.

[0062] The first fluid channel 291 may also be coupled to the eleventh diaphragm valve 250, for example, coupled to the central port. The first fluid channel 291 may also be coupled to the twelfth diaphragm valve 260, for example, coupled to the central port.

[0063] In an optional embodiment, the coupling valve assembly 200 further includes a first pressure sensor 281, which is coupled to the fluid inlet 110 and configured to measure a first pressure of the input fluid. The pressure sensor 281 can be coupled to the fluid inlet 110 through a first fluid channel 291, for example, between the fluid inlet 110 and the eleventh diaphragm valve 250. In another optional embodiment, the coupling valve assembly 200 further includes a second pressure sensor 282, which is coupled to the fluid outlet 120 and configured to measure a second pressure of the output fluid.

[0064] Figure 3A cross-sectional view of a diaphragm valve 231, 232, 241, 242, 250, 260, 271-276 included in a coupling valve assembly 200 according to one or more embodiments of the present disclosure is shown, and the diaphragm valves are shown in an intermediate position between its open and closed positions. In practice, according to the techniques described below, the valve will be closed as a default position and opened when needed.

[0065] The diaphragm valve includes a body 201 coupled to a valve assembly 200. The diaphragm valve also includes a diaphragm 310 disposed in the body 201 and configured to allow fluid flow between a center port 306 and a side port 307 when placed in an open position and to prevent fluid flow between the center port 306 and the side port 307 when placed in a closed position.

[0066] The diaphragm valve further comprises a piston 304 arranged along a longitudinal axis 315 and coupled to the diaphragm 310. The diaphragm valve further comprises a spring 314 arranged along the longitudinal axis 315 and in contact with the piston 304 at one end, the spring being urgeable at an opposite end by the driver 301. The driver 301 is configured to move the opposite end of the spring 314 along the longitudinal axis 315 in response to a received control signal so as to obtain the open diaphragm position and the closed diaphragm position.

[0067] The diaphragm valve 231, 232, 241, 242, 250, 260, 271-276 may further include a valve front portion 308 and a valve rear portion 305, in which case both are part of the valve body 201. The valve diaphragm 310 is fixedly held between the front portion 308 and the rear portion 305 of the valve body 201.

[0068] In one example of operating the diaphragm valves 231, 232, 241, 242, 250, 260, 271-276, a closing procedure from an "open" position is initiated. The circuitry (such as a microprocessor) included in the valve unit 100 receives a control signal from a control unit 410 in the chromatographic device indicating the desire to close the valve. The circuitry causes the driver 301 (e.g., a stepper motor) to move the spring housing 313 forward, thereby pushing the spring 314, which pushes the piston 304, which presses the diaphragm 310 into the seat 309, thereby closing the central port 306 from the side port 307. The central port 306 is typically a port for fluid inflow, but it can also be a port for outflow. When the diaphragm 310 reaches the seat 309, the piston 304 is prevented from moving further, but the driver 301 keeps pushing, thereby compressing the spring 314, which gives an increased force on the diaphragm 310 for closing the valve. When the spring housing 313 reaches a certain position, the position marker closure 302 is detected by the position sensor closure 303. The stepper motor can then be stopped, or if necessary, moved a known amount of additional steps to increase the force applied to the diaphragm 310 even further.

[0069] In an embodiment, some of the diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 included in the coupling valve assembly 200 have high requirements for short movement time and some have lower requirements for speed, but higher requirements for closing force. The diaphragm valves with high requirements for short movement time can stop at the mark. The diaphragm valves with lower requirements for speed but higher requirements for closing force can move an additional fixed distance. The behavior of the valve with respect to the mark can be fully configurable from the control unit software, that is, the hardware is exactly the same. For example, in the coupling valve assembly 200 of this article, two types of valve behaviors can be provided at different positions within the coupling valve assembly 200.

[0070] In one example of operating a diaphragm valve 231, 232, 241, 242, 250, 260, 271-276, an opening procedure from a "closed" position is initiated. The driver 301 moves in accordance with a command or in response to a desired control signal indicating the opening of the valve from a control unit 410 in a chromatographic device 400. The driver 301 pulls up a spring housing 313. This releases the spring force until the back portion of the piston 304 engages with the spring housing, and the driver 301 begins to pull at the piston 304. The piston pulls the diaphragm, which in turn is pulled out to the open position. When the position mark opening 312 is detected by the piston sensor opening 311, the driver 301 stops. The driver 301 does not move any additional steps when moving to the open position, but is certainly possible if necessary.

[0071] Figure 44 shows a chromatographic device 400 according to one or more embodiments of the present disclosure. The chromatographic device 400 may generally include at least one inlet 455. The inlet may optionally be coupled to a reservoir 451, which is configured to hold a fluid. The inlet 455 may, for example, be implemented as a tubular element, such as a tube or a hose. The chromatographic device 400 may also include a valve unit 100, which further relates to Figure 1 The valve unit 100 can be coupled to the reservoir 451 via an inlet 455 coupled to the fluid inlet 110. The valve unit 100 can be configured to be coupled to the first column 441 via a first pair of fluid ports 130 and / or to be coupled to the second column 442 via a second pair of fluid ports 140. The first column 441 and / or the second column 442 can be included in the chromatography device 400 or arranged outside the chromatography device 400.

[0072] The chromatography apparatus 400 may further include a smart fill fluid port or fill fluid port 150 configured to couple to a fill port of the first column 441 or the second column 442. The chromatography apparatus 400 may further include a waste fluid port 160 configured to couple to a waste reservoir or drain.

[0073] The chromatographic device 400 may further include a control unit 410, which includes a circuit system, such as a processor and a memory. The memory may contain instructions executable by the processor, whereby the chromatographic device operates to perform any of the steps or methods described herein. Figure 5 The control unit 410 is described.

[0074] The chromatography device 400 may optionally include a separator 470 coupled to the fluid outlet 120 of the valve unit 100 and coupled to a selection of any one of the pH sensor 431, the conductivity sensor 432, and the outlet valve 420. The separator 470 may be configured to direct the fluid received from the injection unit 480 to any one of the pH sensor 431, the conductivity sensor 432, and the outlet valve 420. Optionally, the separator 470 may be communicatively coupled to the control unit and perform coupling of the fluid in response to a control signal from the control unit 410.

[0075] The pH sensor 431 may be communicatively coupled to the control unit 410 and configured to measure the pH of the fluid provided by the separator 470. The chromatography device 400 may further include a conductivity sensor 432, which is communicatively coupled to the control unit 410 and configured to measure the conductivity of the fluid provided by the separator 470. The pH sensor 430 and / or the conductivity sensor 432 may further be configured to provide the measured pH and the measured conductivity to the control unit 410 as control signals, which include the measurement data.

[0076] The chromatography device 400 may further include an outlet valve 420 coupled to the separator 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 separator 470 to the one or more outlets 421-423 in response to a control signal (e.g., a control signal received from the control unit 410).

[0077] Figure 5 A control unit 410 according to one or more embodiments of the present invention is shown. The control unit 410 may take the form of, for example, an electronic control unit, a server, an onboard computer, a fixed computing device, a portable computer, a tablet computer, a handheld computer, a wrist computer, a smart watch, a smart phone, or a smart TV. The control unit 410 may include a processor 412, which is communicatively coupled to a transceiver 404 configured for wired or wireless communication. The control unit 410 may also include at least one optional antenna (not shown in the figure). The antenna may be coupled to the transceiver 404 and configured to transmit and / or transmit 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 one of the selections of a processing circuit system and / or a central processing unit and / or a processor module and / or a plurality of processors configured to cooperate with each other. In addition, the control unit 410 may also include a memory 415. The memory 415 may, for example, include a hard RAM, a disk drive, a floppy disk drive, a flash drive, or other removable or fixed media drive or any other suitable memory selection 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 separator 470. The control unit 410 may be configured to send / receive control signals directly to any of the above-mentioned units or to an external node or to send / receive control signals via a wired and / or wireless communication network.

[0078] The wired / wireless transceiver 404 and / or the wired / wireless communication network adapter may be configured to send and / or receive data values ​​or parameters as signals to and from the processor 412, to and from other external nodes, such as measured pH or conductivity values.

[0079] In an embodiment, the transceiver 404 communicates to external nodes directly or via a wireless communication network.

[0080] In one or more embodiments, the control unit 410 may further include an input device 417 configured to receive input or instructions from a user and send a user input signal indicative of the user input or instructions to the processing component 412 .

[0081] In one or more embodiments, the control unit 410 may also include a display 418 configured to receive a display signal indicating a rendered object (such as a text or graphical user input object) from the processing component 412, and display the received signal as an object, such as a text or graphical user input object.

[0082] In one embodiment, the display 418 is integrated with the user input device 417 and is configured to receive a display signal indicating a rendered object (such as a text or graphical user input object) from the processing component 412 and display the received signal as an object such as a text or graphical user input object, and / or is configured to receive input or indications from a user and send a user input signal indicating the user input or indication to the processing component 412.

[0083] In further embodiments, the control unit 410 may further include and / or be coupled to one or more additional sensors (not shown in the figures) configured to receive and / or obtain and / or measure physical properties associated with the chromatographic device 400 and send one or more sensor signals indicative of the physical properties to the processing component 412.

[0084] In one or more embodiments, processing component 412 is also communicatively coupled to input device 417 and / or display 418 and / or additional sensors.

[0085] Fig. 6A The coupling valve assembly 200 is schematically illustrated operating in a single column up-flow mode for a first column 441 in accordance with one or more embodiments of the present invention. Fig. 6A Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0086] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 1_UP is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the seventh diaphragm valve 273, the tenth diaphragm valve 276, the second diaphragm valve 232, the first diaphragm valve 231, the ninth diaphragm valve 275, and the fifth diaphragm valve 271 are controlled to an open position. Then the first column 441 can be filled or filled with fluid, for example, in preparation for an upcoming chromatography run.

[0087] Figure 6BThe coupling valve assembly 200 is schematically illustrated operating in a single column down flow mode for a first column 441 in accordance with one or more embodiments of the present invention. Figure 6B Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0088] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 1_DOWN is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eighth diaphragm valve 274, the first diaphragm valve 231, the second diaphragm valve 232, and the sixth diaphragm valve 272 are controlled to an open position. Then the first column 441 can be filled or filled with fluid, for example, in preparation for an upcoming chromatography run.

[0089] Figure 6C The coupling valve assembly 200 is schematically illustrated operating in a single column upflow mode for a second column 442 in accordance with one or more embodiments of the present invention. Figure 6C Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0090] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 2_UP is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eighth diaphragm valve 274, the ninth diaphragm valve 275, the fourth diaphragm valve 242, the third diaphragm valve 241, and the tenth diaphragm valve 276 are controlled to an open position. Then the second column 442 can be filled or filled with fluid, for example, in preparation for an upcoming chromatographic run.

[0091] Fig.6D The coupling valve assembly 200 is schematically illustrated operating in a single column down flow mode for a second column 442 in accordance with one or more embodiments of the present invention. Fig.6D Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0092] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 2_DOWN is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the seventh diaphragm valve 273, the third diaphragm valve 241, the fourth diaphragm valve 242, and the fifth diaphragm valve 271 are controlled to an open position. Then the first column 441 can be filled or filled with fluid, for example, in preparation for an upcoming chromatographic run.

[0093] Fig. 7A The schematic diagram shows a coupling valve assembly 200 operating in a dual column continuous flow mode from a second column 442 to a first column 441 according to one or more embodiments of the present invention. Fig. 7A Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0094] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 2_DOWN-1_DOWN is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the seventh diaphragm valve 273, the third diaphragm valve 241, the fourth diaphragm valve 242, the ninth diaphragm valve 275, the first diaphragm valve 231, the second diaphragm valve 232, and the sixth diaphragm valve 272 are controlled to an open position. Then the second column 442 and / or the first column 441 can be filled or filled with fluid, for example, in preparation for an upcoming chromatographic run.

[0095] Figure 7B The schematic diagram shows a coupling valve assembly 200 operating in a dual column continuous flow mode from a first column 441 to a second column 442 according to one or more embodiments of the present invention. Figure 7B Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0096] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal 1_DOWN-2_DOWN is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eighth diaphragm valve 274, the first diaphragm valve 231, the second diaphragm valve 232, the tenth diaphragm valve 276, the third diaphragm valve 241, the fourth diaphragm valve 242, and the fifth diaphragm valve 271 are controlled to an open position. Then the first column 441 and / or the second column 442 can be filled or filled with fluid, for example, in preparation for an upcoming chromatographic run.

[0097] Fig. 8A A coupling valve assembly 200 is schematically illustrated operating in a top bypass mode in accordance with one or more embodiments of the present invention. Fig. 8A Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0098] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal BY_PASS_TOP is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the seventh diaphragm valve 273, the tenth diaphragm valve 276, and the sixth diaphragm valve 272 are controlled to an open position. Then fill, rinse or clean the fluid channel with fluid that provides the top portion of the column, for example, to prepare the fluid channel for an upcoming chromatographic run.

[0099] Figure 8B A coupling valve assembly 200 is schematically illustrated operating in a bottom bypass mode in accordance with one or more embodiments of the present invention. Figure 8B Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0100] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal BY_PASS_BOTTOM is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eighth diaphragm valve 274, the ninth diaphragm valve 275 and the fifth diaphragm valve 271 are controlled to an open position. Then fill, rinse or clean the fluid channel with fluid that provides the bottom portion of the column, for example, to prepare the fluid channel for an upcoming chromatographic run.

[0101] Figure 8CA coupling valve assembly 200 is schematically illustrated operating in a full bypass mode in accordance with one or more embodiments of the present invention. Figure 8C Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0102] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then, for example, a control signal BY_PASS_ALL is received by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the seventh diaphragm valve 273, the tenth diaphragm valve 276 and the sixth diaphragm valve 272, the eighth diaphragm valve 274, the ninth diaphragm valve 275 and the fifth diaphragm valve 271 are controlled to an open position. Then fill, rinse or clean the fluid channels with fluid that provide the top and bottom portions of the column, for example, to prepare the fluid channels for an upcoming chromatographic run.

[0103] Fig. 9 A coupling valve assembly 200 is schematically illustrated operating in a waste mode in accordance with one or more embodiments of the present invention. Fig. 9 Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0104] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. Then a control signal WASTE is received, for example, by a circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the twelfth diaphragm valve 260 is controlled to an open position. Then the fluid is generally provided to a waste container.

[0105] Fig. 10A A coupling valve assembly 200 is schematically illustrated in accordance with one or more embodiments of the present invention in a first column down drain mode. Fig. 10A Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0106] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in the closed position. Then, for example, the control signal 1_UNPACK_DOWN is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to the open position. Then the eighth diaphragm valve 274 and the first diaphragm valve 231 are controlled to the open position.

[0107] Fig. 10BA coupling valve assembly 200 is schematically illustrated in accordance with one or more embodiments of the present invention in a first column up discharge mode. Fig. 10B Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0108] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in the closed position. Then, for example, a control signal 1_UNPACK_UP is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to the open position. Then the seventh diaphragm valve 273, the tenth diaphragm valve 276 and the second diaphragm valve 232 are controlled to the open position.

[0109] Fig. 10C A coupling valve assembly 200 is schematically illustrated in accordance with one or more embodiments of the present invention in a second column down drain mode. Fig. 10C Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0110] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in the closed position. Then, for example, the control signal 2_UNPACK_DOWN is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to the open position. Then the seventh diaphragm valve 273 and the third diaphragm valve 241 are controlled to the open position.

[0111] Fig. 10D A coupling valve assembly 200 is schematically illustrated in accordance with one or more embodiments of the present invention in a second column up discharge mode. Fig. 10D Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0112] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in the closed position. Then, for example, the control signal 2_UNPACK_UP is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to the open position. Then the eighth diaphragm valve 274, the ninth diaphragm valve 275 and the fourth diaphragm valve 242 are controlled to the open position.

[0113] Fig.11A The coupling valve assembly 200 is schematically illustrated operating in a smart fill flow mode or a fill flow mode for a first column 441 according to one or more embodiments of the present invention. Fig.11AFurther illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0114] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. The eleventh diaphragm valve 250 is coupled to the first column. Then, for example, a control signal I_IP is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eleventh diaphragm valve 250, the second diaphragm valve 232, and the sixth diaphragm valve 272 are controlled to an open position. Then the second column 442 can be filled or filled with fluid, for example, in order to prepare for an upcoming chromatographic run.

[0115] Fig. 11B The coupling valve assembly 200 is schematically illustrated operating in a smart fill flow mode or a fill flow mode with respect to the second column 442 in accordance with one or more embodiments of the present invention. Fig. 11B Further illustrating various diaphragm valves and fluid passages included in the coupled valve assembly 200, which further relates to Figure 2 describe.

[0116] In one example, all diaphragm valves 231, 232, 241, 242, 250, 260, 271-276 are initially in a closed position. The eleventh diaphragm valve 250 is coupled to the second column. Then, for example, a control signal 2_IP is received by the circuit system included in the coupling valve assembly 200, and then a group of diaphragm valves are controlled to an open position. Then the eleventh diaphragm valve 250, the fourth diaphragm valve 242, and the fifth diaphragm valve 271 are controlled to an open position. Then the first column 441 can be filled or filled with fluid, for example, in order to prepare for an upcoming chromatographic run.

[0117] In an embodiment, the communication network communicates using wired or wireless communication technologies, which may include at least one of the following: Local Area Network (LAN), Metropolitan Area Network (MAN), Global System for Mobile Networks (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), 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 Seamless Handover Orthogonal Frequency Division Multiplexing (Flash-OFDM), High Capacity Space Division Multiple Access and Mobile Broadband Wireless Access (MBWA) (IEEE802.20) systems, High Performance Radio Metropolitan Area Network (HIPERMAN), Beam Division Multiple Access (BDMA), Worldwide Interoperability for Microwave Access (Wi-MAX) and ultrasonic communications, but are not limited thereto.

[0118] In addition, those skilled in the art recognize that the control unit 410 may include necessary communication capabilities in the form of functions, components, units, elements, etc. for performing the present technical solution. Examples of other such components, units, elements and functions are: processors, memories, buffers, control logic, encoders, decoders, rate matchers, de-rate matchers, mapping units, multipliers, decision units, selection units, switches, interleavers, deinterleavers, modulators, demodulators, inputs, outputs, antennas, amplifiers, receiver units, transmitter units, DSPs, MSDs, TCM encoders, TCM decoders, power supply units, power feeders, communication interfaces, communication protocols, etc., which are appropriately arranged together for performing the present technical solution.

[0119] The processor and / or processing component of the present disclosure may include one or more examples of the following: identical processing circuits, processor modules and multiple processors configured to cooperate with each other, central processing units (CPUs), processing units, processing circuits, processors, application specific integrated circuits (ASICs), microprocessors, field programmable gate arrays (FPGAs), or other processing logic that can interpret and execute instructions. The expression "processor" and / or "processing component" may thus mean that the processing circuits are identical, including multiple processing circuits, such as any, some or all of those processing circuits mentioned above. The processing component may further perform data processing functions for inputting, outputting and processing data, including data buffering and device control functions, such as call processing control, user interface control or the like.

[0120] Finally, it should be understood that the present invention is not limited to the embodiments described above, but also relates to and incorporates all embodiments within the scope of the attached independent claims.

Claims

1. A valve unit (100) for a chromatography device, the valve unit (100) include: a fluid inlet (110), the fluid inlet (110) being configured to receive an input fluid of the valve unit; a fluid outlet (120) configured to provide an output fluid from the valve unit; a first pair of fluid ports (130) configured to be coupled to a first column (441); a second pair of fluid ports (140) configured to be coupled to a second column (442); a filling fluid port (150) configured to be coupled to a filling port of the first column or the second column; Wherein, the fluid inlet, the fluid outlet, the first pair of fluid ports, the second pair of fluid ports and the filling fluid port are configured to be integrated in the valve unit.

2. The valve unit according to claim 1, in, The fill fluid port is a smart fill fluid port.

3. The valve unit according to claim 1 or 2, further comprising: include: A coupling valve assembly (200) is configured to direct fluid between a selection of the fluid inlet, the fluid outlet, the first pair of fluid ports, the second pair of fluid ports, and the fill fluid port in response to one or more control signals.

4. The valve unit according to claim 3, in, The coupling valve assembly includes a set of diaphragm valves (231, 232, 241, 242, 250, 260, 271-276) and a fluid passage, and the coupling valve assembly is configured to guide fluid using selection of the set of diaphragm valves coupled through the fluid passage.

5. The valve unit according to claim 4, in, The fluid channel is formed in a straight shape without branches or forks along a continuous line from the starting point to the end point.

6. The valve unit according to claim 4 or 5, further comprising: include: A control circuit is configured to receive a control signal and control the set of diaphragm valves to an open or closed position.

7. The valve unit according to any one of claims 3 to 6, in, The coupling valve assembly (200) further includes: a first pressure sensor (281), the first pressure sensor (281) being coupled to the fluid inlet (110) and configured to measure a first pressure of the received fluid; A second pressure sensor (282) is coupled to the fluid outlet (120) and is configured to measure a second pressure of the provided fluid.

8. The valve unit according to claim 5, in, The coupling valve assembly (200) is configured to direct a fluid: from a fluid port (241) coupled to a top portion of the second column to a fluid port (231) coupled to a top portion of the first column; or From a fluid port (231) coupled to a first column top portion to a fluid port (241) coupled to a second column top portion.

9. The valve unit according to claim 5, in, The coupling valve assembly is configured to couple the fill fluid port to a fill port of the first column or the second column.

10. A valve unit according to any one of the preceding claims, further comprising: include: A waste fluid port (160) is configured to be coupled to a waste reservoir or drain.

11. A chromatography device (400), wherein the chromatography device (400) include: The valve unit (100) according to any one of claims 1 to 10; A control unit (410), the control unit (410) comprising a circuit system, the circuit system comprising: a processor (412), and A memory (415) comprising instructions executable by the processor (412), whereby the chromatographic device operates to control the valve unit (100) to direct fluid between a selection of the fluid inlet (110), the fluid outlet (120), the first pair of fluid ports (130), the second pair of fluid ports (140) and the fill fluid port (150) by sending one or more control signals to the valve unit (100).

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