Biological treatment system with automatic filter switching and rotary valve for biological treatment system

Abstract

A biological treatment system comprising: a treatment vessel; a plurality of filter housings; a feed pump for moving fluid between the processing vessel and the filtration assembly; and a retention valve within the retention line. The retention valve includes a fluid passage to selectively direct movement of a fluid to at least one of the plurality of filter housings; an osmotic valve is arranged in the osmotic pipeline between the filter shell and the osmotic pump; a pressure sensor disposed in the permeate line, and a controller coupled to the pressure sensor, the retention valve, and the permeate valve. A controller actuates the retention valve and the osmotic valve to direct flow between the processing vessel and the one or more filter housings based on information received from the flow sensor and the pressure sensor, and direct osmotic flow from the filter housings to the osmotic pump.

Description

[0001] Cross - Reference to Related Applications

[0002] This application is a non - provisional application of pending U.S. Provisional Patent Application Serial No. 63 / 433,556, filed on December 19, 2022, the entire content of which is incorporated herein by reference. Technical Field

[0003] The present disclosure generally relates to filtration systems for pharmaceutical or bioprocess applications. More specifically, the present disclosure relates to filtration systems that are capable of selecting between one or more filters in a multi - filter bank for pharmaceutical or bioprocess applications while minimizing or eliminating the presence of hold - up volume. Background Art

[0004] As will be understood by those of ordinary skill in the art, bioreactor systems or processing filtration systems are known systems for culturing cell cultures. Cultures of microorganisms, plants, or animal cells can be used to produce biologically and chemically important substances. Generally, a bioreactor or processing filtration system can use perfusion culture, which uses a cell retention device to continuously replenish the cell culture medium, remove waste, and harvest products while retaining the cells within the bioreactor or process filtration system.

[0005] The production process of biologics has evolved through a large amount of process intensification. Eukaryotic and microbial cell cultures for producing recombinant proteins, virus - like particles (VLPs), gene therapy particles, and vaccines now include cell growth technologies that can achieve cell growth of 100e6 cells / ml or higher. This is achieved using a cell retention device that can remove metabolic waste and update the culture with additional nutrients. One of the most common cell retention methods is to use alternating tangential flow (ATF) with hollow fiber filtration to perfusion - culture bioreactor cultures.

[0006] Many commercial products are produced using biological processes. For example, using scaled-up reactors and other equipment, commercial-scale drug production can be carried out. So-called biologics are drugs or other compounds that are produced or isolated from living entities such as cells or tissues. Biologics can consist of proteins, nucleic acids, or complex combinations of these substances. They may even include living entities such as cells. To produce biologics on a commercial scale, complex and expensive equipment is required. For example, in the pharmaceutical and biologic industries, various processes are required before the final product is obtained. For example, in the case of biologics, cells can be grown in growth chambers, etc., and nutrients may need to be carefully formulated into the growth chamber. The waste produced by the cells must also be removed from the fermentation chamber on a controlled basis. As another example, biologics produced by living cells or other organisms may need to be extracted and concentrated. This process may involve various filtration and separation techniques.

[0007] Filtration is generally performed to separate, clarify, modify, and / or concentrate fluid solutions, mixtures, or suspensions. In the biotech and pharmaceutical industries, filtration is crucial for the successful production, processing, and testing of new drugs, diagnostics, and other bioproducts. For example, in the process of manufacturing biologics using animal or microbial cell cultures, filtration is carried out to clarify, selectively remove, and concentrate certain components from the culture medium, or to modify the culture medium before further processing. Filtration can also be used to increase productivity by maintaining perfusion in the culture at high cell concentrations.

[0008] When a filter is used in a bioprocessing system, its permeability decreases over time. When the permeability of the filter drops below a certain level, the filter medium must be replaced. Filter replacement during a filtration operation is usually complex and represents an interruption of the filtration process, along with associated product loss and reduced productivity. Filter replacement in a sterile system can also lead to partial or total contamination of the system.

[0009] In addition, existing filtration systems often suffer from generating a retention volume larger than desired and having dead tube segments in the wet fluid path. Both of these problems can have an adverse impact on product recovery, separation efficiency, the volume of fluid required (cleaning, rinsing, and processing), system cost, the footprint required, and the ease of cleaning and disinfecting the system.

[0010] It is in view of these problems that the present disclosure is provided. Summary of the Invention

[0011] The summary of the present disclosure is provided for ease of understanding, and those skilled in the art will understand that each of the various aspects and features of the present disclosure can be advantageously used alone in some cases, or in combination with other aspects and features of the present disclosure in other cases. Inclusion or non-inclusion of elements, components, etc. in the present invention content does not imply a limitation on the scope of the claimed subject matter.

[0012] The disclosed system helps to alleviate problems associated with filter replacement required during continuous filtration operations. The disclosed system also reduces or eliminates the formation of trapped volumes in dead legs of pipe fittings, valves, etc., which typically form when the filtration flow path is changed, such as during a filter replacement operation.

[0013] Disclosed is a biological treatment system, comprising: a treatment container; a filtration assembly including a plurality of filter housings; a feed pump coupled to the plurality of filter housings for moving fluid between the treatment container and the filtration assembly; a retention valve within a retention pipeline coupled between the treatment container and the plurality of filter housings, the retention valve including a fluid passage that is controlled to selectively direct the movement of fluid to at least one of the plurality of filter housings; a permeate valve within a permeate pipeline coupled between the plurality of filter housings and a permeate pump; a pressure sensor disposed in the permeate pipeline; and a controller coupled to the pressure sensor, the retention valve, and the permeate valve. The controller can execute instructions for actuating the retention valve and the permeate valve to direct the flow between the treatment container and a selected one of the plurality of filter housings based on information received from the pressure sensor, and to direct the permeate flow from a selected one of the plurality of filter housings to the permeate pump.

[0014] In some embodiments, the system further includes a pneumatic valve coupled between an air pressure source and a plurality of pneumatically actuated pumps associated with respective ones of the plurality of filter housings. Of course, this is not critical, and different pumping arrangements (i.e., non-pneumatically activated) can be used.

[0015] In some embodiments, a flow sensor is disposed in the retention pipeline for monitoring the flow rate of the feed entering and leaving the treatment container.

[0016] In some embodiments, the retention valve is a rotary retention valve having a rotor with a fluid passage, and the rotor is rotatable to orient the fluid passage so as to fluidly connect the inlet of the rotary retention valve to a selected outlet of the rotary retention valve.

[0017] In some embodiments, the rotary retention valve includes a plurality of outlets, and each of the plurality of outlets is fluidly coupled to a respective one of the plurality of filter housings.

[0018] In some embodiments, the fluid passage includes a plurality of fluid passages, and the selected outlet includes a plurality of selected outlets, and the rotor is rotatable to orient the plurality of fluid passages to fluidly connect the inlet of the rotary retention valve to the plurality of selected outlets.

[0019] In some embodiments, the permeation valve is a rotary permeation valve having a rotor with fluid passages, and the rotor is rotatable to orient the fluid passages to fluidly connect the inlet of the rotary permeation valve to the selected outlet of the rotary permeation valve.

[0020] In some embodiments, the inlet of the rotary permeation valve is fluidly coupled to a permeation line.

[0021] In some embodiments, the retention valve is a rotary retention valve having a housing and a rotor disposed within the housing, the rotor including a cylindrical portion and a conical portion, the conical portion being disposed within a corresponding conical portion of the housing and being configured to rotate about a rotational axis therein.

[0022] In some embodiments, the retention valve is a rotary retention valve having a housing and a cylindrical rotor disposed within the housing, the cylindrical rotor including a plurality of fluid passages for selectively fluidly coupling the inlet of the rotary retention valve to a selected one of a plurality of outlets of the rotary retention valve.

[0023] In some embodiments, the rotary retention valve includes an extension disposed through the housing, the extension being coupled to an actuator controllable by a controller to change the rotational position of the rotor so as to orient at least one of the plurality of fluid passages in the rotor to couple the inlet of the rotary retention valve to a desired one of the plurality of outlets of the rotary retention valve, wherein each of the plurality of outlets is fluidly coupled to a corresponding one of a plurality of filter housings.

[0024] A rotary valve for a bioprocessing system, comprising: a housing including a housing body and a housing cover, the housing body including a plurality of fluid outlets, and a rotor disposed within the housing body and having fluid passages, the rotor being rotatable within the housing body to fluidly connect a fluid inlet to a selected one of the plurality of fluid outlets.

[0025] In some embodiments, the rotor further includes an extension member configured to pass through the housing and coupleable to an actuator for rotating the rotor.

[0026] In some embodiments, the fluid passage includes a plurality of fluid passages.

[0027] In some embodiments, the plurality of fluid passages includes three parallel fluid passages.

[0028] In some embodiments, each of the plurality of fluid channels includes a bend, the geometry of which is configured to facilitate laminar flow through the valve.

[0029] In some embodiments, an inlet is provided in the housing cover and is fluidly coupled to an inlet portion of the fluid channel.

[0030] In some embodiments, the inlet is oriented to direct flow into the fluid channel along the axis of rotation of the rotor.

[0031] In some embodiments, the inlet is provided in the housing body and is oriented orthogonally to the axis of rotation of the rotor.

[0032] In some embodiments, the fluid channel includes a plurality of fluid channels configured such that the rotor is rotatable to a first predetermined position in which the inlet is fluidly coupled to a first pair of selected fluid outlets of the plurality of fluid outlets.

[0033] In some embodiments, the rotor is rotatable to a second predetermined position in which the inlet is fluidly coupled to a second pair of selected fluid outlets of the plurality of fluid outlets.

[0034] These and other features and advantages of the present disclosure will become apparent from the following detailed description, and the scope of the claimed invention is set forth in the appended claims. Although the following disclosure is given in terms of aspects or embodiments, it should be understood that the various aspects may be claimed individually or in combination with aspects and features of any other embodiment. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Non-limiting embodiments of the present disclosure are described by way of example with reference to the accompanying drawings, which are schematic and not intended to be drawn to scale. The drawings are provided for illustrative purposes only, and the dimensions, positions, sequences, and relative sizes reflected in the drawings may vary. For purposes of clarity and simplicity, not every element is labeled in each figure, nor is every element of each embodiment shown, and in such cases no illustration is required to enable a person of ordinary skill in the art to understand the present disclosure.

[0036] The detailed description will be better understood in conjunction with the accompanying drawings, in which like reference numerals represent like elements, as follows:

[0037] Figure 1 is a schematic diagram of a bioprocessing system including a processing vessel and a plurality of filter elements.

[0038] Figure 2 is for Figure 1 an exemplary valve of a bioprocessing system;

[0039] Figures 3A - 3F are various views of an exemplary valve in a biological treatment system for Figure 1 ;

[0040] Figures 4A - 4I are various views of another exemplary valve used in Figure 1 a biological treatment system; and

[0041] Figures 5A - 5J are various views of yet another exemplary valve used in Figure 1 a biological treatment system. DETAILED DESCRIPTION

[0042] The following detailed description should be read with reference to the drawings, which depict illustrative embodiments. It should be understood that the present disclosure is not limited to the specific embodiments described, as these may vary. All devices and systems and methods discussed herein are examples of apparatus and / or systems and / or methods implemented in accordance with one or more features of the present disclosure. Each example of an embodiment is provided by way of explanation and is not the only way of implementing these features, but merely as an example. Thus, reference to an element or structure or feature in the drawings must be understood as a reference to an example of an embodiment of the present disclosure and should not be construed as limiting the present disclosure to the specific element, structure, or feature shown. Other examples of ways of implementing the disclosed features will occur to those of ordinary skill in the art upon reading the present disclosure. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made in the present disclosure without departing from the scope or spirit of the present subject matter. For example, features shown or described as part of one embodiment can be used with another embodiment to yield yet another embodiment. Accordingly, the present subject matter is intended to cover such modifications and variations that fall within the scope of the appended claims and their equivalents.

[0043] Embodiments of the present disclosure generally relate to systems and methods for perfusing cell cultures, which involve alternating fluid flow between a processing vessel and one or more filtration devices. Fluids, such as suspension cell cultures, pass through the filtration devices, which act as alternating tangential flow (ATF) filtration devices as they move back and forth between the processing vessel and the filtration devices. When the fluids flow through the filters, they are separated into (I) a permeate flow containing material that has passed through the membranes of the tangential flow filtration devices, and (II) a feed / retentate flow that has not passed through the membranes of the tangential flow filtration devices.

[0044] A decrease in filter permeability can be measured by the increased pressure required to push fluid through one or more filters. The vacuum or pressure increase can be measured by a pressure measuring device and can be used for automatic redirection of flow from fouled filters to new filters.

[0045] The disclosed system employs one or more rotary valves in the hold-up, permeation, and / or gas supply lines, which minimizes the hold-up volume in the system during filter switching operations. The use of the disclosed rotary valves enables instant switching between filters in a multi-filter arrangement. The rotary valve used as a hold-up and / or permeation valve switches the flow to and from the first filter to the next filter in the filter queue while closing the flow to the remaining filters, such that no valuable product is lost once the flow is redirected from the first filter to the next filter.

[0046] Reference Figure 1 Embodiments of a bioprocessing system 1 will now be described. The system 1 may include a processing vessel 2 (a bioreactor in one non-limiting exemplary embodiment) containing a fluid 4, a filtration assembly 6 including a plurality of filter housings 81, 82, 83, 84, and a control system 10. The fluid 4 (also referred to as the feed) may contain, for example, cells, cell debris, cell metabolites including waste metabolites, expressed proteins, and the like. It should be understood that although the system 1 will be described with four filter housings, the system may have more or fewer filter housings (and filters) without departing from the present disclosure.

[0047] The filter housings 81, 82, 83, 84 may be individually coupled to a hold-up valve 12 via hold-up lines 141, 142, 143, 144. The hold-up valve 12 may be coupled to the processing vessel 2 via a combined hold-up line 16. The filter housings 81, 82, 83, 84 are also individually coupled to a permeation valve 18 via permeation lines 201, 202, 203, 204. The permeation valve 18 may be coupled to a permeation pump 22 via a combined permeation line 24. The permeation pump 22 may be coupled to a collection vessel (not shown) for collecting and retaining the permeate received from the filter housings 81, 82, 83, 84.

[0048] System 1 can be configured to provide alternating tangential flow (ATF) filtration of fluid 4 in processing container 2. Thus, filter housings 81, 82, 83, 84 can contain hollow fiber filter elements that can be used to separate permeate from fluid 4 received from processing container 2, and system 1 can return the fluid (retentate) to the processing container. In the illustrated embodiment, separate filter housings 81, 82, 83, 84 can be coupled to respective separate pumps 261, 262, 263, 264, which in the illustrated embodiment are pneumatically operated diaphragm pumps, although this is not critical and other types of pumps (i.e., non-pneumatically actuated) can be used. Pumps 261, 262, 263, 264 are coupled to filter housings 81, 82, 83, 84 at ends opposite retentate lines 141, 142, 143, 144. It should be understood that although the ATF filtration arrangement is shown and described above. However, ATF filtration can be achieved by diaphragm pumps or by various different methods of alternating flow through the filter. Without departing from the present disclosure, the system can also be arranged for tangential flow filtration (TFF).

[0049] Pumps 261, 262, 263, 264 can be used to move fluid 4 from container 2 through the hollow fiber filter elements in separate filter housings 81, 82, 83, 84 and into the pumps, and then reverse the fluid flow from the pumps through the hollow fiber filter elements in the filter housings back to container 2. In this way, an alternating tangential flow of fluid is created through the hollow fiber filter elements. It can be understood that the alternating flow of retentate between pumps 261, 262, 263, 264 and container 2 passes through the lumen side of the hollow fiber filter elements, while the permeate passes through the walls of the hollow fiber filter elements and is directed out through permeate lines 201, 202, 203, 204 associated with each filter housing 81, 82, 83, 84.

[0050] When system 1 circulates fluid 4 through filtration assembly 6, the hollow fiber filter elements disposed in filter housings 81, 82, 83, 84 remove or separate various materials (e.g., cell debris, soluble and insoluble cell metabolites, and other products produced by cells, including expressed proteins, viruses, virus-like particles (VLPs), exosomes, lipids, DNA, or other small particles) (collectively referred to as "permeate") from fluid 4 and return the cells to processing container 2 to allow the reaction in the processing container to continue. Removal of waste metabolites allows the cells to continue to proliferate in processing container 2, thus allowing the cells to continue to express recombinant proteins, antibodies, or other biomaterials of interest.

[0051] In non-limiting illustrative embodiments, pumps 261, 262, 263, 264 are pneumatic diaphragm pumps. It should be understood that other types of pumps (e.g., centrifugal magnetic suspension pumps, positive displacement pumps, peristaltic pumps, membrane pumps, etc.) may be used without departing from the spirit of the present disclosure. Similarly, osmotic pump 22 may be any of a variety of pump types, including centrifugal magnetic suspension pumps, positive displacement pumps, peristaltic pumps, membrane pumps, etc.

[0052] In the illustrated embodiments, one or more of pumps 261, 262, 263, 264 may be pneumatically actuated by feeding gas (e.g., air) through reversible intake / exhaust lines 281, 282, 283, 284 associated with each pump. Intake / exhaust lines 281, 282, 283, 284 may be coupled to pumps 261, 262, 263, 264 such that when gas, such as from air source 29a, passes through lines 281, 282, 283, 284, it causes the diaphragm in the pump to expand, causing fluid to move in a direction toward and through the hollow fiber filter elements in filter housings 81, 82, 83, 84. The filtered fluid thus moves toward processing vessel 2. When gas passes through intake / exhaust lines 281, 282, 283, 284, such as being drawn back by vacuum source 29b, the diaphragm retracts, causing fluid from processing vessel 2 to be drawn into pumps 261, 262, 263, 264 through the hollow fiber filter elements in filter housings 81, 82, 83, 84.

[0053] In the illustrated embodiments, intake / exhaust lines 281, 282, 283, 284 are coupled to gas valve 30, which in turn is coupled to gas supply 29a and vacuum source 29b via combined gas line 32. Two-way flow control of the gas through gas line 32 may be adjusted by control system 10 via a suitable solenoid valve (not shown). This two-way flow control of the gas may be repeated to draw fluid back and forth from container 2, through filter assembly 6, and into pumps 261, 262, 263, 264, successively causing the above-described alternating flow tangentially through the hollow fiber filter elements in filter housings 81, 82, 83, 84.

[0054] In some embodiments, flow sensor 34 is coupled to combined retentate line 16, while pressure sensor 36 is coupled to combined permeate line 24. Flow sensor 34 and pressure sensor 36 may also be coupled to control system 10 such that the control system may use information from the sensors to control one or more aspects of system 1. Control system 10 may also be coupled to gas valve 30, retentate valve 34, and permeate valve 36 to allow the control system to control fluid flow through system 1.

[0055] Advantageously, the control system 10 is operable to selectively direct and redirect the flow of feed 4 from the processing vessel 2 to one or more of the hollow fiber filter elements in filter housings 81, 82, 83, 84. It will be appreciated that during a filtration operation, over time, the lumens of the filter elements will foul as material clogs the lumens of the filter elements. As fouling develops, an increasing level of suction pressure is required to draw permeate from filter housings 81, 82, 83, 84. This suction pressure can be monitored by the control system 10 via the pressure sensor 36 in the combined permeate line 24, and when it is determined that the pressure meets or exceeds a predetermined value, the control system 10 can switch the operation from the fouled filter to a clean filter.

[0056] For example, during a filtration process, the flow will typically be directed through fewer than all of the filter housings 81, 82, 83, 84 at any given time. Thus, in the case where the flow is directed through the first of the filter housings (e.g., 81) and the control system 10 determines that the negative pressure measured by the pressure sensor 36 in the combined permeate line 24 has reached a predetermined value (indicating that the hollow fiber filter element in filter housing 81 has reached the end of its useful life), the control system 10 can automatically adjust the positions of the gas valve 30, the hold valve 12, and the permeate valve 18 such that the flow from the processing vessel 2 is directed to another filter housing (e.g., 82, 83, 84). Thus, the first filter housing can be taken "offline", and the hollow fiber filter element in filter housing 81 can be replaced without affecting the continuous filtration operation of the system 1.

[0057] In other embodiments, such as when the size of the hollow fiber filter is not sufficient to accommodate the volume of the fluid 4 being filtered, two filters (e.g., 81, 82) can be used simultaneously. In this case, once the control system 10 determines that the pressure in the combined permeate line 24 has reached a predetermined value measured by the pressure sensor 36 (again indicating that the hollow fiber filter elements in filter housings 81, 82 have reached the end of their useful life), the control system 10 will automatically adjust the positions of the gas valve 30, the hold valve 12, and the permeate valve 18 such that the flow from the processing vessel 2 is directed to another set of filter housings (e.g., 83, 84). Thus, the first and second filter housings 81, 82 can be taken "offline", and the hollow fiber filter elements in filter housings 81, 82 can be replaced without affecting the continuous filtration operation of the system 1.

[0058] The control system 10 may include a microprocessor (e.g., a programmable logic controller (PLC)) that includes circuitry enabling the microprocessor to execute instructions to actuate the retention valve 12, the permeate valve 18, and the gas valve 30 to direct the flow of fluid 4 between the processing vessel 2 and a selected one (or subset) of the plurality of filter housings 81, 82, 83, 84 based on information received from flow sensors and pressure sensors, and to direct the permeate flow from a selected one (or subset) of the plurality of filter housings. A non-transitory storage medium / memory may be associated with the processor for storing system parameters and / or instructions used by the processor.

[0059] The retention valve 12, the permeate valve 18, and the gas valve 30 may be of the same design, or they may be of different designs. In some embodiments, the retention valve 12, the permeate valve 18, and the gas valve 30 are all of a design that includes a single inlet and a plurality of selectable outlets. The retention valve 12, the permeate valve 18, and the gas valve 30 may be disposable, or they may be permanent and may be provided as part of a tube set for aseptic applications that is gamma or steam sterilized. In some embodiments, the retention valve 12, the permeate valve 18, and the gas valve 30 may be coupled to a linear or rotary low-pressure servo / stepper actuator (not shown) controlled by the control system 10.

[0060] Now referring Figure 2 to, a translucent view of the valve 50 used as one or more of the retention valve 12, the permeate valve 18, and the gas valve 30 will be described in more detail. As described above, the valve 50 may include an inlet 52 and a plurality of outlets 541, 542, 543, 544. Although the illustrated valve 50 (and the valves to be described subsequently) includes four outlets, it should be understood that this is not restrictive and the valve 50 according to the present disclosure may have any number of outlets.

[0061] The illustrated valve 50 is a rotary valve having a housing 56 that includes an inlet 52 and a plurality of outlets 541, 542, 543, 544. The housing 56 may also include an internal cavity 58 that receives a rotor 60 having a rotational axis "C". The rotor is rotatable within the housing 56 about the axis "C" such that when the rotor rotates about its rotational axis, one or more internal fluid channels 62 may connect the inlet 52 to one or more of the plurality of outlets 541, 542, 543, 544. In the illustrated embodiment, the internal fluid channel 62 fluidly connects the inlet 52 to the first outlet 541. The rotor 60 may also have a rotational position in which the inlet is not fluidly coupled to any of the plurality of outlets 541, 542, 543, 544 ( Figure 2The "closed" position shown). It can be seen that when the rotor 60 rotates to the individual rotational positions "1", "2", "3", "4", the inlet 52 can be selectively aligned with the pipe fittings associated with each of the plurality of filter housings 81, 82, 83, 84. As described above, the rotor 60 can be coupled to a servo / stepper actuator (not shown) controlled by the control system 10 such that the control system can change the filter through which the fluid 4 from the processing vessel 2 will be directed. The valve 50 can be a single-use or reusable type. The reusable model can be made of stainless steel with silicone or rubber seals suitable for steam sterilization. The disposable valve body can be made of rigid plastic and the seals can be made of thermoplastic elastomer or silicone for a complete seal of the fluid or gas path. All materials should be resistant to high temperatures, chemicals, and steam or gamma-ray sterilization processes. The valve 50 can have inlets and outlets of different diameters with different types of connection points such as Luer connections, barb connections, sanitary connections, etc.

[0062] Figures 3A - 3F An embodiment of a rotary valve 150 used as one or more of the retention valve 12, the permeation valve 18, and the gas valve 30 is shown. The rotary valve 150 includes an inlet 152 and a plurality of outlets 1541, 1542, 1543, 1544. When implemented as part of the system 1, the inlet 152 can be directly coupled to the combined retention line 16 (when used as the retention valve 12), the combined permeation line 24 (when used as the permeation valve 18), or the combined gas line 32 (when used as the gas valve 30), while the outlets 1541, 1542, 1543, 1544 can be coupled to individual retention lines, individual permeation lines, or individual gas lines.

[0063] The rotary valve 150 of this embodiment can have a housing 156, which includes a housing body 158 and a housing cover 161. The housing body 158 and the housing cover 161 can together form an internal cavity 159 that receives and encapsulates the rotor 160. It can be seen that the rotor 160 has a cylindrical upper portion 1601 and a conical lower portion 1602. The internal cavity 159 has a complementary shape such that the conical lower portion 1602 of the rotor is located in the conical portion of the cavity and is guided by the conical portion of the cavity.

[0064] The housing cover 161 can include the inlet 152, while the housing body 158 can include the plurality of outlets 1541, 1542, 1543, 1544. In the illustrated embodiment, the inlet 152 is aligned with the rotational axis "C-C" of the rotor 160, while the outlets are angled at an angle β with respect to the axis "C-C". The orientation of the inlet and outlets can be arranged as required for the physical placement of the valve. Even under elevated pressures, the spacing between the port positions must allow for closure between the ports.

[0065] The rotor 160 can rotate within the cavity 158 about the axis "C-C" such that when the rotor 160 rotates about its rotational axis "C-C", one or more internal fluid channels 162 in the rotor can selectively connect the inlet 152 to one or more of the plurality of outlets 1541, 1542, 1543, 1544. The fluid channel 162 has an inlet end 1621 that is aligned with the inlet 152. Both the inlet end 1621 and the inlet 152 are aligned with the axis "C-C" such that fluid received through the inlet 152 is directed to the inlet end 1621 of the fluid channel 162 regardless of the rotational position of the rotor 160. When the rotor 160 rotates, the outlet end 1622 of the fluid channel 162 can selectively align with one or more of the plurality of outlets 1541, 1542, 1543, 1544 such that fluid received through the inlet urchased 152 can be directed to one or more of the plurality of outlets 1541, 1542, 1543, 1544 based on the rotational position of the rotor 160. It can be seen that the inlet end 1621 and the outlet end 1622 are connected by a smooth bend, which facilitates laminar flow of the fluid therethrough and minimizes or prevents turbulence. Since each of the plurality of outlets 1541, 1542, 1543, 1544 can be associated with a particular one of the plurality of filter housings 81, 82, 83, 84, connecting the inlet 152 to a particular outlet 1541, 1542, 1543, 1544 in turn connects the inlet to a selected one of the filter housings.

[0066] The housing body 158 can include an opening 159 through which an extension member 164 extends in a direction opposite to the inlet 152 of the housing cover 161. In the illustrated embodiment, the opening 159 and the extension member 164 are aligned with the axis "C-C" such that rotation of the extension member 164 causes the rotor 160 to rotate about the axis "C-C". Arranged in this way, the rotor 160 can be rotated to separate rotational positions such that the fluid channel 162 aligns the inlet 152 with one or more of the plurality of outlets 1541, 1542, 1543, 1544, each outlet being connectable to a fitting associated with one of the plurality of filter housings 81, 82, 83, 84. In some embodiments, the rotor can also have a rotational position in which the fluid channel 162 does not allow fluid to flow from the inlet 152 to any of the plurality of outlets 1541, 1542, 1543, 1544.

[0067] The extension member 164 can be coupled to a servo / stepper actuator (not shown) controlled by the control system 10 such that the control system can change the rotational position of the rotor 160 to orient the fluid channels so as to couple the inlet 152 to the desired one or more of the plurality of outlets 1541, 1542, 1543, 1544, each of which can be associated with one of the filter housings 81, 82, 83, 84. The servo / stepper actuator can precisely align the inlet 152 with one or more of the plurality of outlets 1541, 1542, 1543, 1544 at a desired speed. The switching speed from one filter to another may be important for more sensitive cell cultures.

[0068] Figures 4A - 4F An embodiment of a rotary valve 250 used as one or more of the retention valve 12, the permeation valve 18, and the gas valve 30 is shown. The rotary valve has an inlet 252 and a plurality of outlets 2541, 2542, 2543, 2544. When implemented as part of the system 1, the inlet 252 can be directly coupled to the combined retention line 16 (when used as the retention valve 12), the combined permeation line 24 (when used as the permeation valve 18), or the combined gas line 32 (when used as the gas valve 30), while the outlets 2541, 2542, 2543, 2544 can be coupled to individual retention lines, individual permeation lines, or individual gas lines.

[0069] The rotary valve 250 of this embodiment can have a housing 256, which includes a housing body 258 and a housing cover 261. The housing body 258 and the housing cover 261 can together form an internal cavity 259 that receives and encapsulates the rotor 260. It can be seen that the rotor 260 is generally cylindrical, and the internal cavity 259 of the housing body 258 has a complementary shape such that the rotor 260 is located within the cylindrical internal cavity 259 and is guided by the cylindrical internal cavity. The housing cover 261 includes a cylindrical ridge 263 that fits within a cylindrical recess 265 in the rotor 260 to maintain the desired orientation of the rotor 260 as the rotor rotates within the housing body 258.

[0070] The housing cover 261 includes the inlet 252, while the housing body 258 includes the plurality of outlets 2541, 2542, 2543, 2544. In the illustrated embodiment, the inlet 252 is aligned with the rotational axis "C-C" of the rotor 260, and the outlets are oriented orthogonally to the axis "C-C". It can be seen that the inlet 252 and the plurality of outlets 2541, 2542, 2543, 2544 are oriented radially outward from the rotational axis "C-C" of the rotor 260 and are evenly spaced from each other.

[0071] The rotor 260 is rotatable within the cavity 258 about the axis "C-C" such that when the rotor 260 rotates about its axis of rotation "C-C", the internal fluid passage 262 in the rotor can selectively connect the inlet 252 to one or more of the plurality of outlets 2541, 2542, 2543, 2544. The fluid passage 262 has an inlet end 2621 that is in fluid communication with the inlet 252. The inlet end 2621 of the fluid passage is aligned with the axis "C-C". In the illustrated embodiment, the outer end 2521 of the valve inlet 252 is orthogonal to the axis "C-C", thereby allowing the inlet 252 of the valve 250 to be coupled to a pipe fitting that is oriented orthogonal to the axis "C-C". Inside the housing cover 261, a curved portion orients the inner end 2522 of the inlet 252 to be aligned with the inlet end 2621 of the fluid passage such that fluid received through the valve inlet 252 is directed to the inlet end 2621 of the fluid passage 262 regardless of the rotational position of the rotor 260. It can be seen that the curved portion between the inlet end 2621 and the outlet end 2622 facilitates laminar flow of the fluid therethrough and minimizes or prevents turbulence. When the rotor 260 rotates, the outlet end 2622 of the fluid passage 262 can selectively align with one of the plurality of outlets 2541, 2542, 2543, 2544 such that fluid received through the inlet 252 can be directed to one or more of the plurality of outlets 2541, 2542, 2543, 2544 based on the rotational position of the rotor 260. In the illustrated embodiment, the outlet end 2622 can seal a selected one of the plurality of outlets 2541, 2542, 2543, 2544 through an O-ring (not shown) that is receivable in a circular groove 264 provided in the rotor 260 in the area surrounding the outlet end 2622 of the fluid passage 262. Since each of the plurality of outlets 2541, 2542, 2543, 2544 can be associated with a particular one of the plurality of filter housings 81, 82, 83, 84, connecting the inlet 252 to a particular outlet 2541, 2542, 2543, 2544 in turn connects the inlet to a selected one of the filter housings.

[0072] The housing body 258 may include an opening 259 through which the extension member 264 extends in a direction opposite to the inlet 252 of the housing cover 261. In the illustrated embodiment, the opening 259 and the extension member 264 are aligned with the axis "C-C" such that rotation of the extension member 264 causes the rotor 260 to rotate about the axis "C-C". Arranged in this way, the rotor 260 can be rotated to a separate rotational position such that the fluid passage 262 aligns the inlet 252 with one or more of the plurality of outlets 2541, 2542, 2543, 2544, each of which can be coupled to a pipe fitting associated with one of the plurality of filter housings 81, 82, 83, 84. In some embodiments, the rotor may also have a rotational position in which the fluid passage 262 does not allow fluid to flow from the inlet 252 to any of the plurality of outlets 1541, 1542, 1543, 1544.

[0073] All rotary valves disclosed herein can be configured with a single inlet and a single outlet. In some embodiments where the filtration area of a single filter is insufficient to meet the requirements of a particular application, the user can select two active filters to receive fluid simultaneously, doubling the filtration area. For example, if filters 1 and 2, which are actively operating, become fouled, the PLC can command the flow to be redirected to filters 3 and 4. The disclosed valves are modular and can accept a rotor with one inlet and one outlet or one inlet and two outlets to enable the flow to be directed to two filters simultaneously.

[0074] The extension member 264 can be coupled to a servo / stepper actuator (not shown) controlled by the control system 10 such that the control system can vary the rotational position of the rotor 160 to orient the fluid passage and thereby couple the inlet 252 to the desired one or more of the plurality of outlets 2541, 2542, 2543, 2544, each of which can be associated with one of the filter housings 81, 82, 83, 84. Based on the positions of the plurality of outlets 2541, 2542, 2543, 2544, the actuator can be pre-programmed for a particular rotational movement. Feedback from the actuator encoder can ensure precise speed and port alignment from one position to another.

[0075] Figures 5A - 5JAn embodiment of a rotary valve 350 is shown that serves as one or more of the retention valve 12, the permeation valve 18, and the gas valve 30. The rotary valve 350 includes an inlet 352 and a plurality of outlets 3541, 3542, 3543. When implemented as part of an embodiment of the system 1 that includes three separate filters 81, 82, 83, the inlet 352 can be directly coupled to the combined retention line 16 (when serving as the retention valve 12), the combined permeation line 24 (when serving as the permeation valve 18), or the combined gas line 32 (when serving as the gas valve 30), and the outlets 3541, 3542, 3543 can be coupled to separate retention lines, separate permeation lines, or separate gas lines.

[0076] The rotary valve 350 of this embodiment can have a housing 356 that includes a housing body 358 and a housing cover 361. The housing body 358 and the housing cover 361 can together form an internal cavity 359 that receives and encapsulates the rotor 360. It can be seen that the rotor 360 is generally cylindrical, and the internal cavity 359 of the housing body 358 has a complementary shape such that the rotor 360 is located within the internal cavity 359 and is guided by the internal cavity.

[0077] The housing cover 361 includes the inlet 352, and the housing body 358 includes a plurality of outlets 3541, 3542, 3543. In the illustrated embodiment, the inlet 352 and the plurality of outlets 3541, 3542, 3543 are oriented orthogonally to the axis "C-C". The 352 and the plurality of outlets 3541, 3542, 3543 are also oriented radially outward from the rotational axis "C-C" of the rotor 360 and are evenly spaced from each other.

[0078] The rotor 360 of this embodiment includes a plurality of internal fluid channels 3621, 3622, 3623 that are generally oriented parallel to each other. The rotor 360 can rotate within the cavity 358 about the axis "C-C" such that when the rotor 360 rotates about its rotational axis "C-C", one or more of the internal fluid channels 3621, 3622, 3623 in the rotor can selectively connect the inlet 352 to one or more of the plurality of outlets 3541, 3542, 3543. Since each of the plurality of outlets 3541, 3542, 3543 can be associated with a specific one of the plurality of filter housings 81, 82, 83, connecting the inlet 352 to a specific outlet 3541, 3542, 3543 in turn connects the inlet to a selected one of the filter housings.

[0079] The housing body 358 can include an opening 359( Figure 5E )), and an extension member 364 of the rotor 360( Figure 5F)extends through the opening. In the illustrated embodiment, the opening 359 and the extension member 334 are aligned with the axis "C-C" such that rotation of the extension member 364 causes the rotor 360 to rotate about the axis "C-C". Arranged in this way, the rotor 360 can be rotated to separate rotational positions ( Figure 5G - Fig. FI), such that the fluid channels 3621, 3622, 3623 align the inlet 352 with one or more of the plurality of outlets 3541, 3542, 3543, each outlet of which can be coupled to a fitting associated with one of the plurality of filter housings 81, 82, 83. In Figure 5G , a first rotational position of the rotor 360 aligns the channel 3622 such that fluid can pass between the inlet 352 and the outlet 3542. In Figure 5H , a second rotational position of the rotor 360 aligns the channel 3623 such that fluid can pass between the inlet 352 and the outlet 3541. In Figure 5I , a rotational position of the rotor 360 aligns the channel 3621 such that fluid can pass between the inlet 352 and the outlet 3543. In some embodiments, the rotor 360 may also have a rotational position ( Figure 5J ) in which the fluid channel 332 does not permit flow from the inlet 352 to any of the plurality of outlets 3541, 3542, 3543. As previously described, the rotary valve 350 can be modular such that it can be used with a variety of different rotor configurations. For example, the rotary valve 350 can be incorporated with a rotor configured to couple between a single inlet and a single outlet (i.e., using only a single filter at any one time). The rotary valve 350 can also be incorporated with a rotor configured to couple between a single inlet and a plurality of outlets (i.e., in the case of using multiple filters simultaneously).

[0080] The extension member 364 can be coupled to a servo / stepper actuator (not shown) controlled by the control system 10 such that the control system can change the rotational position of the rotor 360 to orient the channels 3621, 3622, 3623 to couple the inlet 352 to a desired one or more of the plurality of outlets 3541, 3542, 3543, each outlet of which can be associated with one of the filter housings 81, 82, 83. In some embodiments, a plurality of valves 350 can be connected in series. This series arrangement provides a variety of options for facilitating the connection of filters in a multi-filter system.

[0081] Although what is disclosed herein has been described by way of specific embodiments and their applications, those skilled in the art can make various modifications and variations thereto without departing from the scope of the disclosure set forth in the claims.

[0082] It should be understood that the present disclosure is set forth in this application with varying degrees of detail. For those of ordinary skill in the art, in some cases, details that are unnecessary for understanding the present disclosure or details that make other details difficult to understand may have been omitted. The terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting beyond the scope of the appended claims. Unless otherwise defined, technical terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure pertains. According to the present disclosure, all devices and / or methods disclosed and claimed herein can be made and implemented without undue experimentation.

[0083] The various features, aspects, etc. of the container or processing system can be used independently of each other or in combination. It should be understood that the containers and / or systems disclosed herein can be implemented in many different forms and should not be construed as limited to the embodiments shown in the drawings, such as the embodiments described herein. Instead, these embodiments are provided to enable the present disclosure to convey to those skilled in the art certain aspects of the containers and / or processing systems formed in accordance with the various principles of the present disclosure.

[0084] It should be understood that, as described herein, an "embodiment" (as shown in the drawings) can refer to an illustrative representation of an environment or article or component in which the disclosed concepts or features can be provided or embodied, or to a representation of the manner in which the concepts or features can be provided or embodied only. However, such shown embodiments will be understood as examples (unless otherwise stated), and other ways of embodying the described concepts or features, such as those that can be understood by those of ordinary skill in the art when learning the concepts or features from the present disclosure, are within the scope of the present disclosure. In addition, it should be understood that although the drawings may show one or more embodiments of concepts or features together in a single embodiment of an environment, article, or component that incorporates these concepts or features, these concepts or features should be understood to be (unless otherwise stated) independent and separate from each other and are shown together for convenience and are not intended to be limited to coexistence or co-use. For example, a feature shown or described as part of one embodiment can be used alone or in combination with one or more other features to yield yet another embodiment. Accordingly, the subject matter is intended to cover such modifications and variations that fall within the scope of the appended claims and their equivalents.

[0085] In view of the foregoing, it should be understood that the various embodiments shown in the drawings have several separate and independent features, each of which has at least a unique benefit individually, and these benefits are desirable but not critical for the containers, systems, and related methods disclosed herein. Therefore, in order to achieve at least some of the desirable features and / or benefits described herein, not all of the various individual features described herein need to be present. Only one of the various features may be present in a container or system formed in accordance with the various principles of the present disclosure. Alternatively, one or more features described with reference to one embodiment may be combined with one or more features of any other embodiment provided herein. That is, any feature described herein can be mixed and matched to produce a hybrid design, and such hybrid design is within the scope of the present disclosure. In addition, throughout the present disclosure, reference numerals are used to indicate the general elements or features of the disclosed embodiments. The same reference numerals may be used to denote elements or features that are not identical in form, shape, structure, etc. However, they provide similar functions or benefits. Additional reference numerals (e.g., letters, as opposed to numbers) may be used to distinguish similar elements or features from each other.

[0086] The foregoing discussion has broad applications and is presented for purposes of illustration and description and is not intended to limit the present disclosure to one or more forms disclosed herein. It should be understood that various additions, modifications, and substitutions may be made to the embodiments disclosed herein without departing from the concepts, spirit, and scope of the present disclosure. In particular, it will be apparent to those skilled in the art that the principles of the present disclosure may be embodied in other forms, structures, arrangements, proportions, and other elements, materials, and components without departing from its concepts, spirit, or scope or features. For example, for purposes of simplifying the present disclosure, various features of the present disclosure are combined together in one or more aspects, embodiments, or configurations. However, it should be understood that the various features of certain aspects, embodiments, or configurations of the present disclosure may be combined in alternative aspects, embodiments, or configurations. Although the present disclosure is presented in terms of embodiments, it should be understood that not all of the various individual features of the subject matter need to be present in order to achieve at least some of the desired features and / or benefits of the subject matter or these individual features. Those skilled in the art will understand that the present disclosure may be used with many modifications or variations to the structures, arrangements, proportions, materials, components, etc. used in the practice of the present disclosure, which are particularly adapted to specific environmental and operational requirements. For example, elements shown to be formed integrally may be composed of multiple parts, or elements shown as multiple parts may be formed integrally, the operation of the elements may be reversed or otherwise varied, and the size or dimensions of the elements may be varied. Similarly, although operations or acts or processes are described in a particular order, this should not be construed as requiring such a particular order, or that all operations or acts or processes are to be performed to achieve the desired result. Additionally, other embodiments are within the scope of the appended claims. In some cases, the acts recited in the claims may be performed in a different order and still achieve the desired result. Accordingly, the presently disclosed embodiments are considered to be illustrative in all respects and not restrictive, and the scope of the claimed subject matter is indicated by the appended claims and is not limited to the specific embodiments or arrangements described above or described or illustrated herein. In view of the foregoing, the various features of any embodiment may be used and may be claimed either individually or in combination with the features of that embodiment or any other embodiment, and the scope of the subject matter is indicated by the appended claims and is not limited to the foregoing description.

[0087] In the foregoing description and the claims below, the following will be understood. The phrases “at least one,” “one or more,” and “and / or” as used herein are open-ended expressions that are both conjunctive and disjunctive in operation. The terms “a,” “an,” “the,” “first,” “second,” etc. do not exclude a plurality. For example, the term “a” or “an” entity as used herein refers to one or more of such entities. Thus, the terms “a” (or “an”), “one or more,” and “at least one” may be used interchangeably herein. All directional references (e.g., proximal, distal, upper, lower, upward, downward, left, right, lateral, longitudinal, front, back, top, bottom, above, below, vertical, horizontal, radial, axial, clockwise, counterclockwise, and / or the like) are for identification purposes only to assist the reader in understanding the disclosure, and / or to distinguish regions of related elements from one another, and do not limit the related elements, particularly with respect to their position, orientation, or use in the disclosure. Unless otherwise expressly specified, connection references (e.g., attached, coupled, connected, and joined) shall be construed broadly and may include intermediate members between elements and relative movement between elements. Thus, a connection reference does not necessarily infer that two elements are directly connected and in a fixed relationship to each other. Identification references (e.g., primary, secondary, first, second, third, fourth, etc.) do not imply importance or priority but are used to distinguish one feature from another.

[0088] The appended claims are hereby incorporated by reference into this detailed description, with each claim standing on its own as a separate embodiment of the disclosure. In the claims, the term “comprising” does not exclude the presence of other elements, components, features, regions, wholes, steps, operations, etc. Moreover, although the individual features may be included in different claims, these features may be advantageously combined, and inclusion in different claims does not indicate that a combination of features is infeasible and / or disadvantageous. Further, a singular reference does not exclude a plural. The reference numerals in the claims are provided merely as illustrative examples and should not be construed as limiting the scope of the claims in any way.

Claims

1. A biological treatment system, comprising: A treatment container; A filtration assembly including a plurality of filter housings; A feed pump coupled to the plurality of filter housings for moving fluid between the treatment container and the filtration assembly; A retention valve within a retention pipeline coupled between the treatment container and the plurality of filter housings, the retention valve including a fluid passage that is controlled to selectively direct the movement of fluid to at least one of the plurality of filter housings; A permeation valve within a permeation pipeline coupled between the plurality of filter housings and the permeation pump; A pressure sensor disposed in the permeation pipeline; And A controller coupled to the pressure sensor, the retention valve, and the permeation valve, the controller executing instructions for actuating the retention valve and the permeation valve to direct flow between the treatment container and a selected one of the plurality of filter housings based on information received from the pressure sensor, and to direct permeation flow from a selected one of the plurality of filter housings to the permeation pump.

2. The system according to claim 1, further comprising a pneumatic valve coupled between an air pressure source and a plurality of pneumatic actuating pumps associated with respective ones of the plurality of filter housings.

3. The system according to claim 2, wherein a flow sensor is disposed in the retention pipeline for monitoring the flow rate of the feed entering and leaving the treatment container.

4. The system according to claim 1, wherein The retention valve is a rotary retention valve having a rotor with a fluid passage, the rotor being rotatable to orient the fluid passage to fluidly connect the inlet of the rotary retention valve to a selected outlet of the rotary retention valve.

5. The system according to claim 4, wherein, The rotary retention valve includes a plurality of outlets, and each of the plurality of outlets is fluidly coupled to a respective one of the plurality of filter housings.

6. The system according to claim 5, wherein, The fluid passage includes a plurality of fluid passages, and the selected outlet includes a plurality of selected outlets, and the rotor is rotatable to orient the plurality of fluid passages to fluidly connect the inlet of the rotary retention valve to the plurality of selected outlets.

7. The system according to claim 1, wherein The permeation valve is a rotary permeation valve having a rotor with a fluid passage, the rotor being rotatable to orient the fluid passage to fluidly connect the inlet of the rotary permeation valve to a selected outlet of the rotary permeation valve.

8. The system according to claim 7, wherein, The inlet of the rotary permeation valve is fluidly coupled to the permeation pipeline.

9. The system according to claim 1, wherein The retention valve is a rotary retention valve having a housing and a rotor disposed within the housing, the rotor including a cylindrical portion and a conical portion, the conical portion being disposed within a corresponding conical portion of the housing and being configured to rotate about a rotational axis therein.

10. The system according to claim 1, wherein The retention valve is a rotary retention valve having a housing and a cylindrical rotor disposed within the housing, the cylindrical rotor including a plurality of fluid passages for selectively fluidly coupling the inlet of the rotary retention valve to a selected one of the plurality of outlets of the rotary retention valve.

11. The system according to claim 9, wherein, The rotary retention valve includes an extension portion configured to pass through the housing, the extension portion being coupled to an actuator controllable by the controller to change the rotational position of the rotor, thereby orienting at least one of a plurality of fluid channels in the rotor to couple the inlet of the rotary retention valve to a desired one of a plurality of outlets of the rotary retention valve, wherein each of the plurality of outlets is fluidly coupled to a respective one of the plurality of filter housings.

12. A rotary valve for a biological treatment system, comprising: A housing including a housing body and a housing cover, the housing body including a plurality of fluid outlets; And A rotor disposed within the housing body and having fluid channels, the rotor being rotatable within the housing body to fluidly connect a fluid inlet to a selected one of the plurality of fluid outlets.

13. The valve according to claim 12, wherein the rotor further includes an extension member configured to pass through the housing and coupleable to an actuator for rotating the rotor.

14. The valve according to claim 13, wherein, The fluid channels include a plurality of fluid channels.

15. The valve according to claim 14, wherein, The plurality of fluid channels include three parallel fluid channels.

16. The valve according to claim 14, wherein, Each of the plurality of fluid channels includes a bend, the geometry of the bend being configured to facilitate laminar flow through the valve.

17. The valve according to claim 12, wherein, The inlet is disposed in the housing cover and is fluidly coupled to an inlet portion of the fluid channels.

18. The valve according to claim 12, wherein The inlet is oriented to direct flow into the fluid channels along the rotational axis of the rotor.

19. The valve according to claim 12, wherein, The inlet is disposed in the housing body and is oriented orthogonally to the rotational axis of the rotor.

20. The valve according to claim 12, wherein The fluid channels include a plurality of fluid channels configured such that the rotor can be rotated to a first predetermined position in which the inlet is fluidly coupled to a first pair of selected fluid outlets of the plurality of fluid outlets.

21. The valve according to claim 20, wherein, The rotor can be rotated to a second predetermined position in which the inlet is fluidly coupled to a second pair of selected fluid outlets of the plurality of fluid outlets.

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