Method for integrating sterile connections and barriers onto stackable devices - Patent Application 20070122999

Abstract

The valve comprises a rotary genderless valve (500) having a body (502) with a body hole (524); a body cover (510) for attachment to the body, the body cover having a cover hole (522) and optionally an alignment hole (514); a handle (504) that moves from a closed position to an open position actuated by a rotary motion; a rotary slide (528) attached to the partially rotatable handle, the rotary slide having an elastomeric slide with a rotary slide hole (526); and optionally a second genderless valve having a second rotary slide and a second rotary slide hole, the rotary slide hole and the second rotary slide hole being in fluid communication with each other.

Description

[Technical Field]

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 379,336, filed October 13, 2022, which is incorporated by reference in its entirety.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates to filtration. More particularly, embodiments described herein relate to connectors and valves for filtration cartridges. [Background technology]

[0003] Many downstream filtration products, such as the Viresolve® Pro Magnus Device family sold by EMD Millipore Corporation, Burlington, Massachusetts, USA, have a cassette-style design, allowing multiple devices to be assembled within a single holder. This stackable design allows users to size the assembly to fit their needs—eliminating waste—while maintaining a smaller footprint and reduced workspace. However, assembling multiple devices within the holder exposes them to the ambient room environment, potentially contaminating them with microorganisms. To combat contamination, users often clean the devices with a cleaning solution after assembly, assemble the devices in a clean environment, or rely on downstream sterile filters to remove contaminants. In recent years, the industry has shifted to offering devices and products that are delivered pre-sterilized. Furthermore, these devices often include sterile connections to further reduce the risk of contamination to the device and / or process. By integrating pre-sterilized and sterilely connected devices, users can assemble the devices in an uncontrolled environment without compromising the sterility of the flow path. Current products on the market attach external sterile connectors to the device and provide an external manifold for connecting multiple devices together, however, this approach presents many problems for the user, including (but not limited to) increased cost, increased hold-up, reduced ease of use, reduced capacity, reduced durability, and increased risk of connection issues, i.e., leakage and loss of sterility.

[0004] Small filters are manually assembled for parallel flow with support plates and associated equipment, then tested and, if necessary, sterilized at the user's site, often at considerable cost, inconvenience, and risk. If the manual assembly fails the required tests, the work must be repeated. The mechanical components of larger, more complex filtration systems are generally cleaned and reused by replacing only the filter. Some previous disposable assemblies offered also rely on relatively immovable components, i.e., mechanically secured with fixed and / or rigid tubing.

[0005] Large-area individual membrane filters are supported in flat or cylindrical configurations. Alternatively, pleated membrane filters are arranged in compact housings. Flat membrane holders are large for a given filter area, typically non-disposable, and require disassembly, cleaning, reassembly, and integrity testing with each filter change. The fragile membrane pleats create stress concentrations at the folds, allowing the fragile membrane to flex during use, typically necessitating the use of interleaving flow screens inserted on either or both the upstream and downstream sides. Also, due to concerns about possible breakage at folds, seams, or edges, a separate flat final filter is sometimes used in series with the pleated cartridge for additional assurance in critical applications, such as sterility of pharmaceuticals and intravenous fluids, which increases complexity and cost. Membrane filters containing various polymeric materials are known, and are thin, porous structures with porosities of approximately 50–80% by volume. These membranes are relatively fragile and are used with various mechanical supports or reinforcements. The liquid flow rate through such membranes per unit area is a function of pore size and structure. To obtain high flow rates through filters with pores less than about 1 micron, for example, relatively large filter areas are required. To accommodate these needs, large, sterile individual filters or many smaller individual filters are used simultaneously. For use in some applications, such as life science / pharmaceuticals, membranes and their supporting equipment must be leak-proof.

[0006] Biological fluids that may contain bacteria, microorganisms, etc. are processed in available filter cartridges, which experience significant pressure loss, limiting the volume of biological fluid that can be processed through the cartridge. The degree of pressure loss is closely related to the membrane resistance, which depends on the porosity and pore size, i.e., the pore structure, and the flow path length of the fluid in the cartridge; i.e., the longer the flow path length, the greater the pressure loss.

[0007] Previous prior art attempts to solve these problems have included the use of filtration cartridges formed from multiple stacked filtration modules with separate external housings. Cartridges are undesirable due to their large retention volumes, which result in significant sample loss. Another technique involved filtration cartridges with a feed inlet and permeate outlet located in the central portion of the cartridge. This cartridge requires a fluid deflection plate to direct the incoming feed fluid from the central portion of the cartridge to the peripheral portions of the cartridge. Deflection plates are undesirable because they introduce elements within the cartridge that are not related to its intended function.

[0008] Integrity testing is required for filters. Integrity testing may use a two-component gas system to determine the presence of defects in the membrane or filter device. To perform this type of testing, two-component gas must be flowed across the membrane in tangential flow filtration (TFF), as opposed to normal flow filtration (NFF), also known as dead-end filtration. This type of integrity testing is described in U.S. Patent No. 7,594,425, filed October 10, 2006, and incorporated herein in its entirety. Therefore, if it is desired to perform both NFF filtration and integrity testing within a filtration cartridge, the filtration cartridge must be capable of operating in both TFF and NFF modes.

[0009] For simplicity's sake, it would be desirable to provide a filtration cartridge with a single feed inlet and a single permeate outlet. Furthermore, it would be desirable to provide a cartridge that can operate in both TFF and NFF modes. Furthermore, it would be desirable to provide a filtration cartridge that minimizes components unrelated to its intended function in order to reduce costs. Furthermore, an insert that provides an effective method for connecting filter cartridges and maintaining sterility without a manifold would be an advancement in the art. Furthermore, it would be an advancement in the art to provide a cartridge in which the fluid being processed experiences a lower pressure drop within the cartridge compared to currently available cartridges.

[0010] A rotary genderless valve having a body with a body hole, a body cover for attachment to the body, the body cover having the cover hole and optionally an alignment hole, a handle, the handle having a closed side and an open side actuated by a rotary motion, a rotary slide attached to the partially rotatable handle, the elastomeric slide having a rotary slide hole, and optionally a second genderless valve having a second rotary slide and a second rotary slide hole, the rotary slide hole and the second rotary slide hole being in fluid communication with each other. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] U.S. Patent No. 7,594,425 Summary of the Invention

[0012] Connectors for use in bioprocessing are disclosed. Filtration is at least one bioprocessing step that can be performed using embodiments of the present disclosure. As more fully described in the claims, several embodiments of connectors, also referred to as valves, described herein are disclosed as generally shown in and / or described in connection with at least one of the drawings. Connector embodiments described within the present disclosure, in some embodiments, eliminate the drawbacks summarized above by creating an integrated, gamma-irradiatable sterile connection or sterility barrier within the port or end cap of a stacked cassette device. Any of the connectors, plugs, or inserts described herein can be sterilized by gamma radiation, X-rays, and / or ionizing radiation. These connectors or barriers allow users to assemble the device in a sterile manner, eliminating the need for external manifolds, third-party connectors, and accessories.

[0013] The connectors described herein can be integrated into end caps or ports of, for example, filtration devices, cartridges, and / or holders. Linearly and rotary actuated genderless valves are also disclosed. The connectors and genderless valves described herein are not limited to viral removal cassettes but can also be used in other cassette-type devices within the filtration industry, such as membrane chromatography and purification devices, as well as in other liquid management industries. Various advantages, aspects, novel and inventive features of the present disclosure, as well as details of exemplary embodiments thereof, will be more fully understood from the following description and drawings. [Brief explanation of the drawings]

[0014] [Figure 1] 1 illustrates a front view of a connector according to some embodiments of the present disclosure. [Figure 2] 2 is a cross-sectional view of the connector of FIG. 1 taken along line 2-2 according to some embodiments of the present disclosure. [Figure 3] FIG. 3 is an exploded view of the connector of FIGS. 1-2 according to some embodiments of the present disclosure. [Figure 4] FIG. 4 is a front perspective view of a filtration cassette that can be connected via the connector of FIGS. 1-3 according to some embodiments of the present disclosure. [Figure 5] FIG. 5 is a cross-sectional view of one cassette along line 5-5 according to some embodiments of the present disclosure. [Figure 6] 1 shows a cross-sectional view of two cassettes 200 stacked and connected via connectors 100, according to some embodiments of the present disclosure. [Figure 7] 7A and 7B are front perspective views of a valve according to some embodiments of the present disclosure. [Figure 8] Figures 8A and 8B are front perspective views of the valve of Figures 7C-7D according to some embodiments of the present disclosure. [Figure 9] 9A is a cross-sectional view of the valve 300 of FIG. 7A along line 9-9, further including a complementary valve 300 in a closed position, according to some embodiments of the present disclosure. FIG. 9B is a cross-sectional view of the valve 300 of FIG. 7A along line 9-9, further including a complementary valve 300 in a closed position, according to some embodiments of the present disclosure. [Figure 10] 10A is a cross-sectional view of the valve 300 of FIG. 7D along line 10-10, further including a complementary valve 300 in an open position, according to some embodiments of the present disclosure. FIG. 10B is a cross-sectional view of the valve 300 of FIG. 7D along line 10-10, further including a complementary valve 300 in an open position, according to some embodiments of the present disclosure. [Figure 11] Figure 11A shows a close-up view of the cross section of Figures 9-10 according to an embodiment of the present disclosure. Figure 11B shows a close-up view of the cross section of Figures 9-10 according to an embodiment of the present disclosure. [Figure 12]12A and 12B are exploded views showing two complementary rotary sterile valves in the closed position according to some embodiments of the present disclosure. [Figure 13] Figure 13A shows Figure 12C, which is an exploded view of two complementary rotary valves in an open position, according to some embodiments of the present disclosure. Figure 13B shows Figure 12D, which is an exploded view of two complementary rotary valves in an open position, according to some embodiments of the present disclosure. [Figure 14] 12A-12B show two complementary rotating sterile valves in a closed position in an assembled view, according to some embodiments of the present disclosure. [Figure 15] 12C-12D show, in assembled view, two complementary rotary sterile valves in an open position, according to some embodiments of the present disclosure. [Figure 16] 16 shows an exploded view of the two rotary valves of FIGS. 12-15, according to some embodiments of the present disclosure. FIG. [Figure 17] 1 illustrates a rotary valve having an air gap according to some embodiments of the present disclosure. [Figure 18A] 18 shows an exploded view of two rotary valves, the rotary valve shown in FIG. 17, according to some embodiments of the present disclosure. [Figure 18B] 18 shows an exploded view of two rotary valves, the rotary valve shown in FIG. 17, according to some embodiments of the present disclosure. [Figure 19] 1 shows a partially exploded view of a genderless expandable valve according to some embodiments of the present disclosure. [Figure 20-1] 20 shows two perspective exploded views of the genderless expandable valve of FIG. 19 according to some embodiments of the present disclosure. [Figure 20-2] 20 shows two perspective exploded views of the genderless expandable valve of FIG. 19 according to some embodiments of the present disclosure. [Figure 21]21A and 21B show a slider for use in a genderless expandable valve according to some embodiments of the present disclosure. [Figure 22] 22A-22D show perspective views of the genderless expandable valve of FIGS. 19-21 in open and closed positions according to some embodiments of the present disclosure. [Figure 23A] 23A-23C show cross-sectional views of the genderless expandable valve of FIGS. 19-22 according to some embodiments of the present disclosure. [Figure 23B] 23A-23C show cross-sectional views of the genderless expandable valve of FIGS. 19-22 according to some embodiments of the present disclosure. [Figure 23C] 23A-23C show cross-sectional views of the genderless expandable valve of FIGS. 19-22 according to some embodiments of the present disclosure. [Figure 24] 24A and 24B show partial exploded views of a second genderless expandable valve according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0015] Although specific terminology is used in the following description for clarity, these terms are intended to refer only to the specific structure of the embodiment selected for illustration in the drawings. It should be understood that in the drawings and the following description, like number designations refer to components of similar structure and / or function.

[0016] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0017] As used herein, various devices and components may be described as "comprising" other elements. As used herein, the terms "comprise(s)," "include(s)," "having," "is," "has," "can," "contain(s)," and variations thereof, are intended to be open-ended transitional phrases, terms, or words that do not exclude the possibility of additional elements.

[0018] All ranges disclosed herein are inclusive of the recited endpoints and are independently combinable (e.g., the range "2% to 10%" includes the endpoints, 2% and 10%, and all intermediate values).

[0019] As used herein, approximation can be used to modify any quantitative expression that can be varied without changing the underlying function. Thus, values ​​modified with terms such as "about," "approximately," and "substantially" may not be limited to the exact value specified. The modifier "about" should also be considered to disclose a range defined by the absolute values ​​of the two endpoints. For example, the expression "about 2 to about 4" also discloses a range of "2 to 4."

[0020] It should be noted that some terms used herein are relative terms. For example, the terms "upper" and "lower" are relative in location to one another, i.e., an upper component is located at a higher elevation than a lower component, and should not be construed as requiring a particular orientation or position of the structure. As a further example, the terms "interior," "exterior," "inward," and "outward" are relative to the center and should not be construed as requiring a particular orientation or position of the structure.

[0021] The terms "top" and "bottom" are relative to an absolute reference, i.e., the surface of the Earth. In other words, a top position is always at a higher elevation relative to the surface of the Earth than a bottom position. The term "genderless" within this disclosure refers to the ability to create a fluid flow path without any flow channel protruding into another portion of another flow channel. A "flow channel" or flow path is any passageway capable of allowing the flow of a fluid therethrough.

[0022] Embodiment 1: Bimodal Membrane Insert. The bimodal membrane insert provides a key feature of a method for preventing contamination of devices, e.g., stackable devices, using a sterile barrier. The sterile barrier, e.g., membrane insert, is inserted into a port of the stackable device and secured in place, e.g., by welding and / or an elastomeric seal, e.g., an O-ring, or other means capable of forming an airtight seal between the frame and the stackable device, e.g., cassette, and / or between two adjacent cassettes. In some embodiments, the membrane is welded to the device. The sterile barrier / membrane insert can be positioned within the device throughout transportation, storage, and use. Furthermore, the membrane insert does not require external manipulation by the user to function. The sterile barrier comprises a frame, within which passages are formed to allow flow through the frame structure. Attached to the top of the frame are multiple hydrophobic and / or hydrophilic sterilization-grade membranes. The combination of hydrophilic and hydrophobic membranes allows both water and gas to flow through the assembly during use of the device. When the devices are stacked, another device can be placed and compressed. Opposing membrane inserts positioned between the devices form a separation region within which any biological contaminants, such as microorganisms or bacteria, that contaminate the surface during assembly are trapped between the opposing membrane inserts. This trapping mechanism prevents bacteria from reaching other areas of the device during use, as bacteria cannot pass through any of the membranes comprising this separation region. Furthermore, the amount of fluid leaking from the device when a user removes the device from the holder is significantly reduced. Referring now to the drawings, FIG. 1 shows a front perspective view of a connector 100 according to some embodiments of the present disclosure. The connector 100 includes a housing 101 for creating a bimodal membrane insert, the bimodal insert being formed with a hydrophobic membrane and a hydrophilic membrane capable of allowing liquid and gas flow. As shown, the housing 101 is generally circular in shape, although this need not be the case. In fact, the connector 100 need only fit into a complementary shape within the filtration cassette, as further described below.In some embodiments, the housing 101 comprises an arcuate upper region 115 having an outer rail 105 and an arcuate lower region 111 having an inner rail 106, the arcuate lower region 111 generally having a smaller diameter than the upper region 115. The housing 101 optionally further comprises a plurality of legs 109 extending downwardly and connecting the upper and lower regions 115 and 111. The housing 101 comprises an upper groove (described below) and a lower groove (described below) within the upper region 115, which position the first seal 102 and the second seal 102 below the first seal 102. The first and second seals 102 may be, for example, flexible elastomeric or polymeric O-rings.

[0023] The arcuate upper region 115 accommodates multiple membranes 103, 104. In practice, there may be three or more membranes 103, 104. As shown, the two membranes 103, 104 are concentric and may be the same or different membrane types. In at least one embodiment, membrane 103 may be a hydrophilic, sterilizing-grade membrane, generally described as having a pore size rating of about 0.22 microns or less, and membrane 104 may be a hydrophobic, sterilizing-grade membrane; in some embodiments, both membranes may possess both hydrophilic and hydrophobic properties. In some embodiments, membranes 103, 104, regardless of pore size, are capable of passing an appropriate bacterial retention test. Connector 100 is capable of being sterilized, and connector 100 is also capable of creating and / or maintaining a sterile condition.

[0024] FIG. 2 is a cross-sectional view of the connector 100 of FIG. 1 according to some embodiments of the present disclosure. As shown, the housing 101 further includes an upper groove 112 and a lower groove 114 separated by a groove rail 107. As shown, the first seal 102 and the second seal 102 are disposed within the upper groove 112 and the lower groove 114. As shown, the upper groove 112 and the lower groove 114 may be rectangular, but may optionally be formed as circles. The membranes 103 and 104 are separated by an inner rail 106. The membrane 104 is disposed between the outer rail 105 and the inner rail 106. An outer channel 108 between the inner rail 106 and the outer rail 105 separates the fluid flow from the inner channel 110. The central channel 116 is a region for fluid flow traveling through a central region that is in fluid communication with the inner channel 110.

[0025] FIG. 3 is an exploded view of the connector 100 of FIGS. 1-2 , according to some embodiments of the present disclosure. The housing 101 is shown having empty upper grooves 114 and 112 separated by rails 107, as well as multiple outer and inner channels 108, 110, and a central channel 116. Also shown are two seals 102 and two membranes 103, 104. It should be understood that a fluid, such as a biological fluid, travels through the central channel 116 and / or the inner channel 110 and is filtered as it travels through the membranes 103, 104. In some embodiments, a cassette can have three to six connectors 100. For example, a cassette having two inlets, two outlets, and two vents would include six connectors 100.

[0026] FIG. 4 is a front perspective view of a filtration cassette 200 that can be connected to an adjacent filtration cassette 200 (not shown) via the connectors 100 of FIGS. 1-3 , according to some embodiments of the present disclosure. As shown, there are two connectors 100 on the top surface 202 of the filtration cassette 200. Another connector 100 is shown on the bottom surface 204 of the cassette. It should be understood that a fourth connector 100, not shown, is also present on the cassette 200. It should be further understood that 2, 3, 4, 5, 6, 7, 8... or even more cassettes 200 can be joined together into a single filtration system in any commercially reasonable number, e.g., using a press. It should be further understood that any cassette 200 can include multiple stacked plates 206, each capable of housing a filtration membrane and / or multiple filtration membranes.

[0027] 5 is a cross-sectional view of a cassette 200 taken along line 5-5, according to some embodiments of the present disclosure. As shown, the cassette 200 has two connectors 100 in fluid communication with each other. As can be seen, the lower arcuate regions 111 of the connectors 100 disposed within each cassette 200 abut one another. Also shown are a plurality of filtration membranes 206 surrounding a central channel 116. Other features, including the housing 101, rail 107, and a plurality of outer and inner channels 108, 110, and the central channel 116, are also shown relative to their surroundings. Also shown are two seals 102 and two membranes 103, 104, as well as the outer and inner rails 105, 106.

[0028] FIG. 6 shows a cross-sectional view of two cassettes 200 stacked via connectors 100, according to some embodiments of the present disclosure. It should be understood that when two or more cassettes 200 are stacked, they are in fluid communication via connectors 100. The cassettes need not be joined other than by applying pressure to be in fluid communication. It should further be understood that connectors 100 can be placed in any inlet, outlet, or vent of any of the cassettes 200. Alternatively, a plug (not shown) can be placed in one or more of the multiple filtration cassettes 200. The cassettes 200 can be stackable devices having filtration membranes. For example, cassette 200 can include depth filtration cassettes such as Pellicon®, Pellicon® 2, Pellicon® 3, Natrix® devices, and Millistak+® devices, tangential flow filtration cassettes such as Prostak™ devices, and Viresolve® Pro Magnus devices, all commercially available from EMD Millipore Corporation, Burlington, Massachusetts, USA, and embody a cassette-type configuration. A Natrix® device, such as cassette 200, can include a macroporous cross-linked gel, which includes a polymer formed from the reaction of one or more polymerizable monomers and one or more cross-linking agents. The macroporous cross-linked gel is located within the pores of a support member, and the macropores of the macroporous cross-linked gel are smaller than the pores of the support member. In some embodiments, the composite material is for bioaffinity chromatography. In some embodiments, the composite material is a porous membrane. In some embodiments, the composite material can be a porous polymer gel membrane. In some embodiments, a manifold-less filtration system is disclosed that includes two or more adjacent cassettes in fluid communication with each other via a plurality of connectors.

[0029] Embodiment 2: Linear Disposable Elastomeric Sterile Valve. The linear disposable elastomeric sterile valve embodiment describes a low-profile, genderless valve that can be integrated into stackable cassette-type devices. The linear disposable elastomeric sterile valve embodiment allows for sterile opening of the flow paths of multiple stacked devices, such as those described above, without the need for an external manifold. Furthermore, the linear disposable elastomeric sterile valve allows for isolation of the flow paths of each of multiple stackable devices / cassettes upon disassembly. For example, some of the described connections can be reversed to close the device. Each cassette can be removed from the holder in a generally drip-free manner. The holder includes a top plate and a bottom plate connected by a rod. A hydraulic piston or other hydraulic device compresses the holder, and thus the cassette, between the top and bottom plates, forming a seal between the devices. For example, the Viresolve® Pro Magnus holder is commercially available from EMD Millipore Corporation of Burlington, Massachusetts, USA. Other holders are described in International Publication No. WO 2022108902, which is incorporated in its entirety. A linear disposable elastomeric sterile valve comprises a main body and two complementary valve halves, each housing an elastomeric (or suitably compressible or flexible) slide with a rigid portion and a sterile orifice. This allows for sterile isolation of the flow path in the closed position. The elastomeric slide can be constructed, for example, by placing or otherwise overmolding an elastomeric material, such as silicone, a thermoplastic elastomer, or a thermoplastic polyolefin, onto a frame that provides elastomeric support and / or rigidity, in some embodiments a thermoplastic or thermoset material. A film or release strip can be placed on the elastomeric slide adjacent to the flow path and removed prior to use. A linear genderless valve can be sterilized and prevent the growth of pathogens, i.e., the genderless valve can create and / or maintain a sterile condition.The film may be made of a polymeric material, a plastic film, a plastic sheet, or the like. The polymeric material may be, for example, nylon, polyester, polyolefin, or the like. The film may also comprise a metallized polymeric film, for example, a plastic film coated with aluminum. In some embodiments, the film may be a metal film coated with a polymeric material. In some embodiments, the film may be a metal film. The film forms a sterile barrier for the sterile orifice prior to use. The sterile orifice can be sterilized by steam treatment, gamma irradiation, X-ray, ethylene oxide, or other sterilization processes known to those skilled in the art. The rigid end of the elastomeric slide at least partially covers the flow path to prevent contamination. When the cassettes / devices are stacked and joined or otherwise placed in fluid communication, the two valve halves come together and are compressed in place. The elastomeric slide comprises handles. Pulling both handles opens the flow path between two adjacent devices / cassettes. This can be done simultaneously or separately. During this pulling action, the sterile orifices on either side of the elastomeric slide are pulled out of the film and aligned with the flow passages in the housing of the elastomeric slide. In other words, the genderless valve can include a body, a handle with a closed side and an open side, a port attached to the body, an elastomeric slide attached to the handle, the elastomeric slide with the orifices, and a film sealed or removably attached to the elastomeric slide. Optionally, a second genderless valve has a second orifice, and the orifice and the second orifice can be in fluid communication with each other. When the orifices of the two genderless valves are aligned, optionally, ribbed features molded into the housing, for example, compress the orifices against each other, forming an airtight seal, i.e., between the housing and the sterile orifices. A second compression of the stacked devices / cassettes can optionally be applied by a holder to further compress the airtight seal, forming an even stronger seal.The fluid path of the device / cassette is now open, and the user can process fluid using the device / cassette. Once processing is complete, the user can remove some of the compression from the device. The valve can then be forced to the closed position by the handle. This action once again covers the fluid path using the elastomeric valve. This action, operating the valve from open to closed, isolates the fluid path and generally prevents residual fluid from dripping from the device. The user can then complete the decompression of the fluid pressure and decompression of the holder before removing and discarding the used device / cassette.

[0030] FIG. 7 is a front perspective view of a valve 300 according to some embodiments of the present disclosure. FIG. 7 includes FIG. 7A of the valve 300 and FIG. 7B, which is a mirror image of a complementary valve 300 oriented upside down relative to the valve 300 of FIG. 7A. The valve 300 is a genderless valve and includes a body 302 and a handle 304 having a closed side 304a and an open side 304b. The valve 300 is shown as a genderless valve because neither the valve 300 nor the complementary valve 300 has any portion that protrudes beyond the other to form a fluid connection. The two valves 300 are held together by pressure, such as from a hydraulic press, so that fluid flows through the port 306 of one valve 300 and out the port 306 of the complementary valve 300. As shown, the valves 300 in FIGS. 7A-7B are in a closed position. The valve 300 further includes a port 306 and, optionally, a plurality of body notches 310. 7B, valve 300 further comprises an elastomeric slide 316 and a film 314. Film 314 is attached to elastomeric slide 316. Elastomeric slide 316, which is attached to handle 304, is made from, for example, a silicone material or a thermoplastic elastomer. As shown below, elastomeric slide 317 comprises a valve orifice (shown more clearly below).

[0031] FIG. 8 shows a valve 300 with an associated complementary valve 316, as in FIGS. 7A-7B, but now in the open position, as shown in FIGS. 7C-7D. The elastomeric slide moves linearly when force is applied to the handle; i.e., pulling or pushing the open handle 304b urges the elastomeric slide 316 linearly away from the film 314, exposing the valve orifice 320. Delivery of a fluid, such as a biological fluid, to the port 306 of the valve 300 in FIG. 7C, when both are in the open position, creates a flow path, allowing the fluid to flow, for example, through the valve orifices 320 of both valves 300 and exit the port 306 of the valve 300 in FIG. 7D. The film 314 is a sterile barrier that protects the sterility of the valve orifice 320, which can be sterilized by steam, x-ray, gamma irradiation, ethylene oxide treatment, ozone treatment, and / or other sterilization processes known to those skilled in the art. The port side 318 of the slide may also include one or more chamfered edges, such as a first chamfered edge 330 and / or a second chamfered edge 332.

[0032] 9 is a cross-sectional view of the valve 300 of FIG. 7A taken along line 9-9, further including a complementary valve 300 in a closed position, according to some embodiments of the present disclosure. As shown in FIG. 9, each of the valves 300 includes a sterile orifice 320 in a closed position, with a film 314 disposed thereon.

[0033] 10 is a cross-sectional view of the valve 300 of FIG. 7D along line 10-10, further including a complementary valve 300 in an open position, according to some embodiments of the present disclosure. As shown in FIG. 10, each of the valves 300 includes a sterile orifice 320 in an open position, with the film 314 respectively removed therefrom, creating an open valve state through which liquid supplied to either port 306 can flow.

[0034] FIG. 11 shows a close-up view of the cross section of FIGS. 9-10 according to an embodiment of the present disclosure. FIG. 11A shows a close-up view of two valves 300 in a closed position. FIG. 11B shows a close-up view of two valves in an open position. The bodies 302 of the valves 300 are shown. Each of the bodies 302 of each valve 300 has an inner surface 324. The inner surfaces 324 each have two chamfers 322a that narrow to a thicker body thickness 326 near the valve orifice 320 compared to a thinner body thickness 328 around the periphery of the body 302. Because of the smaller thickness T adjacent the valve orifice 320, an interference fit is formed when the handle (not shown) is pulled in direction F. In other words, the two elastomeric slides 316 fit into a smaller space, providing a tighter seal and enhancing leak tightness.

[0035] Embodiment 3: Rotary Elastomeric Aseptic Valve. The rotary elastomeric aseptic valve embodiment is similar to the linear disposable elastomeric aseptic valve embodiment. The rotary elastomeric aseptic valve is actuated by rotary actuation of a handle, as opposed to a linear manner. Rotary actuation reduces the force required to actuate the valve due to the inherent mechanical advantages of the rotary design. Furthermore, the rotary elastomeric aseptic valve requires much less space on the end cap when assembled into a device / cassette, at least because linear motion is eliminated. The mechanisms for sealing and maintaining sterility of the flow passages and orifices are generally similar. The rotary elastomeric aseptic valve, which is also genderless, can be sterilized, while the genderless valve can maintain sterility.

[0036] FIG. 12A-12B show two complementary rotary elastomeric sterile valves 400 (also referred to as rotary valves 400) in a closed position, according to some embodiments of the present disclosure. FIG. 12A shows a bottom perspective view of the rotary elastomeric sterile valve 400. FIG. 12A shows a top perspective view of the rotary elastomeric sterile valve 400. The two rotary elastomeric sterile valves 400 are complementary because, similar to the linear genderless complementary valves described above, they cooperate to form a channel or circuit for fluid flow. For example, through a channel formed by a rotary valve orifice 420, as described more fully below. The rotary valve 400 is a genderless valve and includes a body 402 and a handle 404 having a closed side and an open side. As shown, the valve 400 in FIGS. 12A-12B is in the closed position, and the handle 404 is designated 404a. In FIG. 12B, the underside of the rotary slide 416 is visible. Alignment holes 414 are optionally provided in the body 402 and body cover 420 to allow for attachment of the valve 400. Other attachment means are available, such as adhesives, ultrasonic welding, overmolding, RF welding, and other attachment means known to those skilled in the art. The holes 414 also aid in aligning the body 402 and body cover 420. FIG. 13 shows two rotary valves 400 in the open position, according to some embodiments of the present disclosure. As shown, the handle 404 is in position 404b, opposite the position 404a described above. The open position is easily recognized in FIG. 12C, as the through-hole can be seen through the rotary orifice 420.

[0037] 12A-12B, showing a cross section of two complementary rotating elastomeric sterile valves 400 in the closed position, according to some embodiments of the present disclosure. As can be seen, the handle 404 is in the closed position 404a. Thus, the rotating slide 428 blocks any fluid that might otherwise migrate to the other rotating sterile valve 400. Each of the bodies 402 also includes at least one internal chamfer or other transition edge 434 near the body bore 424 so that the rotating slide 428 is allowed to slide but remains tight against the body 402.

[0038] 12C-12D, showing a cross section of two complementary rotary elastomeric sterile valves 400 in the open position, according to some embodiments of the present disclosure. As can be seen, the handle 404 is in the open position 404b. The rotary slide 428 is therefore in a position that allows the entry of any fluid that may migrate to the other rotary sterile valve 400. Specifically, the body hole 424, rotary slide hole 426, and cover hole 422 are aligned in both rotary valves 400. It should be understood that many rotary valves 400 can be pressed, assembled, or joined together with a filtration system, similar to the linear valve 300 described above.

[0039] FIG. 16 shows an exploded view of the two rotary valves 400 of FIGS. 12-15 according to some embodiments of the present disclosure. As shown, it should be understood that the two rotary valves 400 are mirror images of one another. As shown, the exploded view shows each of the rotary valves 400 in a closed position. Each of the rotary valves 400 includes a body 402 having a body hole 424 and a body cover 410 having a body cover hole 422, and a handle 404 having a rotary slide 428 or otherwise attached thereto and a rotary slide hole 426. The body cover hole 422 and the body hole 424 are generally concentric when the rotary valve 400 is assembled. The handle 404 having the rotary slide 428 and slide hole 426 is positioned such that the slide hole 426 is not concentric with at least one of the body hole 414 or the body cover hole 422 when the rotary valve 400 is assembled, and the handle 404 is in the closed position. When the handle 404 is in the open position, the slide hole 426, the body hole 414, and the body cover hole 422 are generally concentric, providing a channel or flow path for fluid. The handle 404 can be made of any suitable material, such as a thermoplastic. As shown, the rotating slide 428 includes an arcuate edge 430 such that it can rotate at least partially freely relative to an edge 432 of the body 402 when switching from the closed position to the open position or vice versa. The rotating slide 428 can also include a raised area having chamfered edges 432, 434 adjacent the rotating slide hole 426. Similarly, the rotating body 402 can include internal body chamfers 452, 454 adjacent the body hole 424. The rotating slide 428 can be made of any suitable flexible material, such as a thermoplastic elastomer or silicone. In some embodiments, the rotating slide 428 is thinned to form a gap (as described in more detail below) between the rotating slide 428 and the body cover 410. For example, in some embodiments, the gap is about 0.125 centimeters (cm), or for example, in some embodiments, 0.020 to 0.180 cm, or in some embodiments, 0.010 to 0.100 cm, or in some embodiments, 0.030 to 0.090 cm.It is believed that the air gap prevents any contaminants on the surface of the rotating slide 428 from being transported to another area of ​​the rotary valve 400 during operation of the rotary valve 400. Typically, it is the rotating slide 428 that is thinner to form the air gap.

[0040] FIG. 17 illustrates a rotary valve 500 having a gap 560 according to some embodiments of the present disclosure. The rotary valve 500 is similar to the rotary valve 400. The rotary valve 500 is genderless. In other words, genderless indicates that no part of one rotary valve 500 accepts any part of another rotary valve 500 with which it is in fluid communication. In FIG. 17, the body cover 510 is shown as transparent, but this need not be the case. The body cover 510, whether transparent, translucent, or opaque, can be made of a metal such as stainless steel, or any suitable polymeric material, thermoplastic elastomer, or thermoset material. In this context, this means that the polymeric material can be sterilized while maintaining its durability for all bioprocessing applications. For example, portions of the rotary valve 500 can be sterilized by at least one of ethylene oxide treatment, corona treatment, steam treatment, gamma irradiation, ethyl alcohol, hydrogen peroxide gas, X-ray, or other sterilization processes known to those skilled in the art. Gap 560 is a vertical gap formed by the different heights of rotating slide 528 and chamfered edges 532, 534 (shown in FIG. 18 below) and / or body cover 510. In some embodiments, rotating slide 528 is thinned such that gap 560 is formed between rotating slide 528 and body cover 510. For example, in some embodiments, gap 560 is approximately 0.125 centimeters (cm), or, for example, in some embodiments, 0.020-0.180 cm, or in some embodiments, 0.010-0.100 cm, or in some embodiments, 0.030-0.090 cm. It is believed that any contaminants on the surface of rotating slide 528 are not transported to another area of ​​rotary valve 500 during operation of rotary valve 500 due to the gap. Typically, it is rotating slide 528 that is thinner to form gap 560.

[0041] FIG. 18 shows an exploded view of two rotary valves, the rotary valves 500 shown in FIG. 17 , according to some embodiments of the present disclosure. As shown, it should be understood that the two rotary valves 500 are mirror images of each other. As shown, the exploded view shows each of the rotary valves 500 in a closed position. Each of the rotary valves 500 includes a body 502 having a body bore 524 and a body cover 510 including a body cover bore 522, a handle 504 including or otherwise attached to a rotary slide 528 and a rotary slide bore 526. A port (not shown) is typically attached to, integrally formed with, or otherwise in fluid communication with the body bore 524. The body cover bore 522 and the body bore 524 are generally concentric when the rotary valve 500 is assembled. The handle 504, including the rotating slide 528 and the slide hole 526, is positioned such that, when the rotary valve 500 is assembled, the slide hole 526 is not concentric with at least one of the body hole 514 or the body cover hole 522, and the handle 504 is in the closed position. When the handle 504 is in the open state, the slide hole 526, the body hole 514, and the body cover hole 522 are generally concentric, providing a channel or flow path for fluid. The handle 504 can be made of any suitable material, such as a thermoplastic. As shown, the rotating slide 528 includes an arcuate edge 530 so that it can at least partially rotate freely relative to an edge 532 of the body 502 when switching from the closed position to the open position, or vice versa. The rotating slide 528 may also include a raised region having chamfered edges 532, 534 adjacent the rotating slide hole 526. Similarly, the rotating body 502 may include internal body chamfers 552, 554 adjacent the body hole 524. The rotating slide 528 may be made of any suitable flexible material, such as a thermoplastic elastomer or silicone.

[0042] FIG. 19 shows a partially exploded view of a genderless expandable valve 600 according to some embodiments of the present disclosure. The genderless expandable valve 600 includes an in-line valve 620 and a central valve 630. The central valve 630 can receive a cap 618 at a first end 654 opposite a second end 656. The in-line valve 620 includes an inlet port 606, such as a barbed port. The inlet port 606 may be integrally formed, i.e., a single piece made in a single operation, such as by injection molding or a 3D printing process. Alternatively, the port 606 may include threads (not shown) for threading into a corresponding threaded hole (not shown) in the in-line valve 620. The in-line valve 620 further includes a slider 604 having a slot 636, as described more fully below. A post 616 protrudes from the slider 604 and includes a locating hole 614 for receiving a post, such as from the post 616 on the central valve 630. The central valve 620 further comprises two arcuate members 626, a first arcuate member and a second arcuate member opposite the first arcuate member, as described more fully below. In some embodiments, a second or third in-line valve 620 and / or a central valve 630 can be added to the genderless expandable valve 600. The first and second arcuate members house a slider 604 and a valve disc 624 having disc holes 610 through which fluid flows when the genderless expandable valve 600 is in the open position. The valve disc 624 also includes one or more holes 622 into which a corresponding number of posts from the central valve 630 can fit to assemble the central valve 630. The valve disc 624 is suitably made of any resilient, flexible material, such as a thermoplastic, a thermoplastic olefin, or a thermoplastic elastomer. The disc holes 610 may be covered by a sterile peel strip, as described below.

[0043] The central valve 630 includes a housing 642. The housing 642 includes a housing slot 632 that allows the rotary handle 608 to partially rotate therein. The rotary handle 608 is joined to a hub or is an integral part of the hub, which is housed within the housing 642. For example, the rotary handle 608 may have an interference fit with a hole in the hub or may be a separate part that screws into the hub. The hub also houses a first hub slider 634 on a second end 656 and a second hub slider 638 opposite the first slider 634 located at the second end 654 of the housing 642 of the central valve 630. The first slider 634 and the second slider 638 are held by two arcuate members 626, a first arcuate member and a second arcuate member (not shown) opposite the first arcuate member, similar to the inline valve 620. A disk 624 is also disposed on the first slider 638. The disk 624 also has a peel strip 648 disposed thereon to keep the surface of the disk sterile until the genderless expandable valve 600 is ready for use. An exit port 628 projects from the central valve 630 and is generally perpendicular to the inlet port 606.

[0044] 20-1 and 20-2 show alternative perspective exploded views of the genderless expandable valve 600 of FIG. 19 without the in-line valve 620, according to some embodiments of the present disclosure. In both figures, the disk 624 is shown outside the exploded view for ease of understanding. The figures show the components of the hub assembly. The first figure shows a top-left perspective view of the center valve 630. The slider 634 has a slot 636 and a valve hole 678. The valve hole 678 is surrounded by a thermoplastic olefin or thermoplastic elastomer. For example, the valve hole 678 may be surrounded by silicone rubber. Optionally, the valve hole 678 may transition in height from a thicker portion to a transition region 682 to a lower region 686. The thicker portion and transition region 682 allow the slider 634 to slide more easily from the closed position to the open position while maintaining a leak-tight condition while in the open state. A hole 674 in the central valve 630 leads to the outlet port 628. A hub hole 676 is also shown in the center of the hub 660. The hub 660, with the rotating handle 608, fits inside the housing 642. A second slider 638, with a hole 678 on the opposite side, shows a flat hole 666 surrounded by an elastomer 684, such as silicone rubber, which may be overmolded onto the slider 638. A first arcuate member 662 is shown above the slider 638, and a second arcuate member 664 is shown below the slider 638. An assembly hole 672 is shown connecting the sliders 634, 638 to the cap (not shown) and hub 660. The second view shows an upper right perspective view of the same components, but showing the opposite surface of the components shown in the first perspective view. For example, the back of the slider 634 shows the post 616 and hole 614.

[0045] FIG. 21 illustrates sliders 604, 634, 638 for use in genderless expandable valves according to some embodiments of the present disclosure. FIG. 21A shows a top view of sliders 604, 634, 638, revealing slots 636 that position pins or posts (not shown), allowing them to slide within valve 600 and preventing sliders 604, 634, 638 from being removed from valve 600 during operation. Also shown are holes 678 surrounded by transition regions 682. Transition regions 682 are stepped areas where the surfaces of sliders 604, 634, 638 protrude upward to form a seal with similar areas of corresponding sliders 604, 634, 638. Silicone can be insert molded, overmolded, two-shot molded, transfer molded, liquid injection molded, or cast, or other plastics operations known to those skilled in the art. For example, the areas shown in cross section may be polymeric material and formed by injection molding. Silicone material can then be injected into the areas shown to fabricate sliders 604, 634, 638. In Figure 21B, a cross-sectional view shows transition region 682, which rises from lower surface 686 to upper surface 691 of sliders 604, 634, 638. Flat surface 666 of hole 678 is opposite upper surface 691. Post 616 is also shown.

[0046] FIG. 22 shows a perspective view of the genderless expandable valve 600 of FIGS. 19-20-1 and 20-2, according to some embodiments of the present disclosure. The rotatable handle 608 is in an open position. FIG. 23 shows a cross-sectional view of the genderless expandable valve of FIGS. 19-22, according to some embodiments of the present disclosure. FIG. 23A shows the genderless expandable valve in a closed position. The sliders 604 and 634 are in an open position, as is the rotatable handle 608. As can be seen, the rotatable handle 308 is in an open position in FIG. 23B, and both sliders 604 and 634 are in an open position, allowing fluid flow to enter through the inlet port 606 and exit through the outlet port 628. The silicone region 684 in the slider 638 is in a closed position, providing support to prevent incoming fluid from being forced out of the cap 618. The cap 618 can be removed and replaced with a port (not shown). The genderless expandable valve 600 can then be repositioned with the rotary handle 608 in the closed position, but the slider 638 slid to the open position, allowing fluid flow straight through the genderless expandable valve 600, creating a flow path for, for example, sampling. FIG. 23C shows a front perspective cross-sectional view of the genderless expandable valve 600 in the open position. Also shown is an O-ring 696, which can provide a seal between two adjacent sliders 604, 634, for example. Alternatively, or in addition, an O-ring 696 can be disposed between the slider 638 and the cap 618.

[0047] FIG. 24 shows a partially exploded view of a second genderless expandable valve 700 according to some embodiments of the present disclosure. The second genderless expandable valve 700 includes an inlet port 606 and an outlet port 698. Similar to the genderless expandable valve 600 described above, the slider 604 includes a post 616 for engaging a corresponding hole 614 in the slider 634. The second genderless expandable valve 700 further includes a valve disc 624 having a hole 622 and, optionally, a peel strip 648. A mirror image slider 634 is shown adjacent to the slider 604. The sliders 604 and 634 are joined to form the second genderless expandable valve 700 with an O-ring 696 disposed therebetween. As shown in FIG. 24A, when the sliders 604, 634 are pulled to their outward positions, the second genderless expandable valve 700 is in a closed position. When each of the sliders 604, 634 is pushed inward, it is in an open position, allowing fluid to flow therethrough, i.e., forming a flow path, as shown in Figure 24B. Any of the valve embodiments of Figures 19-24 can also be used in the inlet, outlet, and vent ports of any of the cassettes and systems described above with respect to the other connectors and valves. Any of the embodiments of Figures 19-24 can be integrated as a sterile connector and / or barrier within any of the cassettes or stackable devices described herein.

[0048] While various aspects and embodiments have been disclosed herein, other aspects, embodiments, modifications, and variations will be apparent to those skilled in the art upon reading and understanding the foregoing detailed description. The various aspects and embodiments disclosed herein are for purposes of illustration and not limitation. It is intended that the present disclosure be construed as including all such aspects, embodiments, modifications, and variations insofar as they come within the scope of the appended claims or equivalents thereof.

Claims

1. A rotary genderless valve, a body having a body hole; a body cover for attachment to the body, the body cover having a cover hole and optionally an alignment hole; a handle having a closed side and an open side actuated by a rotational movement; a rotation slide attached to the partially rotatable handle, the rotation slide having an elastomeric slide further comprising a rotation slide hole; Optionally, A rotary genderless valve comprising: a gap formed between the body cover and the rotary slide; and optionally, the rotary genderless valve is joined to a second genderless valve having a second rotary slide and a rotary slide hole, and the rotary slide hole and the second rotary slide hole are fluidly connected to each other.

2. 10. The rotary genderless valve of claim 1, wherein the film is sealed to the elastomeric slide or removably attached to the elastomeric slide.

3. 10. The rotary genderless valve of claim 1, wherein the rotary slide is made of, for example, a silicone material or a thermoplastic elastomer.

4. 2. The rotary genderless valve of claim 1, wherein the thermoplastic elastomer is a polyolefin such as polypropylene, polyethylene, ethylene propylene rubber, ethylene propylene diene rubber, or a block copolymer of polyolefin.

5. 10. The rotary genderless valve of claim 1, wherein the body comprises a body chamfer adjacent the body bore.

6. 10. The rotary genderless valve of claim 1, wherein the rotary slide comprises a raised area adjacent the rotary slide hole.

7. 10. The rotary genderless valve of claim 1, wherein the rotary genderless valve is capable of creating a sterile condition.

8. 10. The rotary genderless valve of claim 1, wherein a gap exists between the rotary slide and the body cover.

9. 10. The rotary genderless valve of claim 1, further comprising a port in fluid communication with the body bore.

10. 3. The rotating genderless valve of claim 2, wherein the rotating genderless valve and film are sterilized.

11. A connector, a housing having an upper surface capable of receiving a plurality of membranes, the plurality of membranes comprising hydrophilic membranes and hydrophobic membranes; at least one groove on the housing for securing at least one seal.

12. 12. The connector of claim 11, wherein the hydrophilic and hydrophobic membranes are sterilizing grade membranes.

13. The connector of claim 11 , wherein the membranes are concentric.

14. The connector of claim 11, further comprising a second groove for securing a second seal disposed below the at least one seal.

15. The connector of claim 11 further comprising a plurality of legs extending from the top surface to the bottom surface.

16. The connector of claim 11 , wherein the first seal and the second seal are flexible.

17. The connector of claim 11 , wherein the connector is disposed within a cassette.

18. The connector of claim 11 , wherein the connector is disposed within a vent, an inlet, or an outlet of the cassette.

19. 12. The connector of claim 11, wherein the hydrophilic and hydrophobic membranes have a pore size rating of 0.22 microns or less.

20. 10. A manifold-less filtration system comprising two or more cassettes in fluid communication with each other via a plurality of connectors according to claim 1.

21. A genderless valve, The main body and a handle having a closed side and an open side; The port attached to the main unit, an elastomeric slide attached to the handle, the elastomeric slide having an orifice and moving linearly when force is applied to the handle; and a film sealed to or removably attached to an elastomeric slide, and optionally a second genderless valve having a second orifice, the orifice and the second orifice being in fluid communication with each other.

22. 22. The genderless valve of claim 21, wherein the film is attached to an elastomeric slide.

23. 22. The genderless valve of claim 21, wherein the elastomeric slide is made of, for example, a silicone material or a thermoplastic elastomer.

24. 22. The genderless valve of claim 21, wherein the film and / or the genderless valve is sterilized.

25. 22. The genderless valve of claim 21, wherein the genderless valve is capable of creating a sterile condition.

26. 24. The genderless valve of claim 23, wherein the thermoplastic elastomer is a polyolefin such as polypropylene, polyethylene, ethylene propylene rubber, ethylene propylene diene rubber, or a block copolymer of polyolefin or silicone.

27. 1. A genderless expandable valve, comprising: an in-line valve having a valve disc, the hole being in the valve disc; a central valve having a slider and a valve disc with a hole, the slider being slidable to an open or closed position; a cap or outlet port; and an in-line valve having an inlet port and a slider, the slider of the in-line valve being slidable to an open position or a closed position to form a flow path through the valve disc of the in-line valve and the valve disc of the central valve together with the central valve when the central valve is in the open position.

28. 30. The genderless expandable valve of claim 27, further comprising a second slider and a hub having a rotation handle for opening the central valve.

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