Multi-channel pinch valve for automated cell engineering cartridge

Abstract

A valve assembly may include a valve body including a plurality of conduits extending through the valve body. A valve assembly may include a plurality of pinch bits configured to translate parallel to a first axis to selectively engage the conduits. A valve assembly may include a plunger comprising: a plunger shaft, a first bit guide configured to actuate a first pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second bit guide configured to actuate a second pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first pinch bit and the second pinch bit in opposite directions.

Description

ATTORNEY DOCKET No. 0132-0338W01MULTI-CHANNEL PINCH VALVE FOR AUTOMATED CELL ENGINEERING CARTRIDGECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Application No. 63 / 725,044, filed November 26, 2024, the entirety of which is incorporated herein by reference.FIELD OF INVENTION

[0002] The present disclosure is directed toward a valve assembly and, in particular, a multichannel pinch valve assembly for an automated cell engineering cartridge.BACKGROUND

[0003] Generally, advanced cell therapies for treating a wide range of diseases have recently become popular. Automation of various processes is involved in producing cell populations for therapy. This includes integration of cell activation, transduction and expansion into a commercial manufacturing platform, for the translation of these important therapies to the broad patient population.

[0004] In such automated cell engineering systems, it is often necessary to control the flow of one or more fluids through various valve constructs to deliver cells, media, vector solutions, etc., to desired areas or chambers of a system. Poppet, or trumpet, valves are often used to control flows through the system. However, poppet valves present risks to sterile integrityof the system that must be addressed (e.g., with one or more filters downstream of each valve). The present disclosure provides the design of a multichannel valve to control fluid flow using with a set number of valve actuators while reducing risk to sterility of the system.SUMMARY

[0005] The techniques presented herein provide an open / close functionality of multiple fluid lines of cell engineering cartridge.

[0006] In an example embodiment, a valve assembly includes a valve body, a plurality of conduits extending through the valve body; a plurality of valves configured to translate parallel to a first axis to selectively engage the conduits; and a plunger comprising: a plunger shaft; a first valve guide configured to actuate a first valve of the plurality of valves in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second valve guide configured to actuate a second valve of the plurality of valves in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to independently translate the first valve and the second valve.ATTORNEY DOCKET No. 0132-0338W01

[0007] In some embodiments of the valve assembly, the first axis is substantially perpendicular to the plurality of conduits.

[0008] In some embodiments of the valve assembly, the first valve guide comprises a first ramp portion and a first horizontal portion, the first ramp portion configured to engage a first valve shoulder of the first valve.

[0009] In some embodiments of the valve assembly, the second valve guide comprises a second ramp portion and a second horizontal portion, the second ramp portion configured to engage a second valve shoulder of the second valve.

[0010] In some embodiments of the valve assembly, the first ramp portion extends in a first ramp direction and the second ramp portion extends in a second ramp direction, wherein the first ramp direction and the second ramp direction are skew lines.

[0011] In some embodiments of the valve assembly, the plunger further comprises a third valve guide configured to actuate a third valve of the plurality of valves parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first valve and the third valve in parallel directions.

[0012] In some embodiments of the valve assembly, the plunger is configured to actuate the valve assembly between a first state, a second state and a third state in response to translating along the first direction.

[0013] In some embodiments of the valve assembly, the assembly of claim 7, wherein the valve assembly further comprises a spring to bias the plunger along the first direction toward the first state.

[0014] In some embodiments of the valve assembly, in the first state, the first valve and the third valve engage corresponding conduits of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduits.

[0015] In some embodiments of the valve assembly, in the first state, the second valve does not engage a corresponding conduit of the plurality of conduits.

[0016] In some embodiments of the valve assembly, in the second state, the first valve and the third valve do not engage corresponding conduits of the plurality of conduits.

[0017] In some embodiments of the valve assembly, in the second state, the second valve engages a corresponding conduit of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduit.

[0018] In some embodiments of the valve assembly, in the third state, the first valve, the second valve, and the third valve do not engage the plurality of conduits.ATTORNEY DOCKET No. 0132-0338W01

[0019] In some embodiments of the valve assembly, a spring barrel maintains the valve assembly in the third state and prevents the plunger from translating.

[0020] In some embodiments of the valve assembly, the plurality of conduits comprise flexible tubing.

[0021] In some embodiments of the valve assembly, each valve of the plurality of valves is configured to engage a corresponding conduit by pinching the corresponding conduit.

[0022] In an example embodiment, a cassette for an automated cell engineering system comprises: a cassette body defining a plurality of valve seats; and a plurality of valve assemblies disposed in the plurality of valve seats, each valve assembly comprising: a valve body; a plurality of conduits extending through the valve body; a plurality of valves configured to translate parallel to a first axis to selectively engage corresponding conduits of the plurality of conduits; and a plunger comprising: a plunger shaft; a first valve guide configured to actuate a first valve of the plurality of valves in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second valve guide configured to actuate a second valve of the plurality of valves in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to independently translate the first valve and the second valve.

[0023] In some embodiments of the cassette, the plurality of valve assemblies includes: a first valve assembly having a first valve configured to engage a first conduit of the plurality of conduits; and a second valve assembly having a second valve configured to engage the first conduit.

[0024] In some embodiments of the cassette, a second valve of the first valve assembly is configured to engage a second conduit of the plurality of conduits and a first valve of the second valve assembly is configured to engage the second conduit.

[0025] In some embodiments of the cassette, each valve assembly of the plurality of valve assemblies further comprises a third valve guide configured to actuate a third valve of the plurality of valves, wherein the third valve of the first valve assembly is configured to engage a third conduit of the plurality of conduits and a third valve of the second valve assembly is configured to engage the third conduit.

[0026] In some embodiments of the cassette, the plurality of valves are configured to selectively allow fluid to flow through the plurality of conduits.

[0027] In some embodiments of the cassette, the plurality of conduits comprise flexible tubing.ATTORNEY DOCKET No. 0132-0338W01

[0028] In some embodiments of the cassette, each valve of the plurality of valves is configured to engage a corresponding the conduit by pinching the conduit.

[0029] In an example embodiment, a method for conducting fluid through a cassette of an automated cell engineering system comprises: translating, via an actuator, a plunger of a valve assembly along a plunger axis; translating, via the plunger, a first valve and a second valve perpendicularly to the plunger axis, wherein the first valve translates independently from the second valve; and opening, via the first valve, a first conduit and simultaneously closing, via the second valve, a second conduit.

[0030] In some embodiments of the method, the method further comprises translating a third valve simultaneously and in parallel with the first valve.

[0031] In some embodiments of the method, the method further comprises opening a third conduit, via a third valve, simultaneously with the opening of the first conduit.

[0032] In some embodiments of the method, closing a conduit comprises pinching the conduit with a corresponding valve.

[0033] In some embodiments of the method, opening a conduit comprises releasing the conduit with a corresponding valve.BRIEF DESCRIPTION OF THE DRAWINGS

[0034] To complete the description and in order to provide for a better understanding of the techniques presented in this application, a set of drawings is provided. The drawings form an integral part of the description and illustrate an embodiment of the present application, which should not be interpreted as restricting the scope of the present application, but just as an example of how the techniques presented herein can be carried out. The drawings comprise the following figures:

[0035] FIG. 1 depicts an automated cell engineering system having a cassette, according to an embodiment.

[0036] FIG. 2 depicts a rear view of the cassette according to FIG. 1.

[0037] FIG. 3A depicts a perspective view of a valve assembly according to an embodiment.

[0038] FIG. 3B depicts a top, cut away view of the valve assembly of FIG. 3 A.

[0039] FIG. 3C depicts an exploded view of the valve assembly of FIG. 3A.

[0040] FIG. 4A depicts a front view of a pinch bit, according to an embodiment.

[0041] FIG. 4B illustrates a side view of the pinch bit of FIG. 4 A.ATTORNEY DOCKET No. 0132-0338W01

[0042] FIG. 5A depicts an isometric view of the upper valve body of the valve assembly of FIG. 3 A.

[0043] FIG. 5B depicts a perspective view of the lower valve body.

[0044] FIGS. 5C-5E depict various views of a pinch cap of the valve assembly of FIG> 3A.

[0045] FIG. 6A depicts a side view of the valve assembly of FIG. 3 A.

[0046] FIG. 6B depicts a plunger and a pinch bit, according to an embodiment.

[0047] FIG. 7A-7C depict a perspective view of the plunger, according to an embodiment.

[0048] FIG. 8A depicts an axial view of the valve assembly in a first state, according to an embodiment.

[0049] FIG. 8B depicts a side view of the valve assembly in the first state, according to an embodiment.

[0050] FIG. 8C depicts an axial view of the valve assembly in a second state, according to an embodiment.

[0051] FIG. 8D depicts a side view of the valve assembly in the second state, according to an embodiment.

[0052] FIG. 9 depicts a side view of the travel of the plunger when actuated between the first state and the second state, according to an embodiment.

[0053] FIG. 10 depicts a side view of the valve assembly in a third state, according to an embodiment.

[0054] FIGS. 11A-11D depict a process for setting the valve assembly to the first state, from the third state according to an embodiment.

[0055] FIG. 12A depicts a perspective view of a valve assembly, according to another embodiment.

[0056] FIG. 12B depicts a side view of the valve assembly of FIG 12 A.

[0057] FIG. 12C depicts a portion of the valve assembly of FIG. 12 A.

[0058] FIG. 13 depicts a perspective view of a plunger and a pinch bit of the valve assembly of FIG. 12 A.

[0059] FIG. 14A depicts a schematic diagram of a fluid pathway of a cassette, according to an embodiment.

[0060] FIG. 14B depicts a chart for determining the pathways of two fluidly connected valve assemblies according to an embodiment.

[0061] Like reference numerals have been used to identify like elements throughout this disclosure.ATTORNEY DOCKET No. 0132-0338W01DETAILED DESCRIPTION

[0062] The following description is not to be taken in a limiting sense but is given solely for the purpose of describing the broad principles of the invention. Embodiments of the invention will be described by way of example, with reference to the above-mentioned drawings showing elements and results according to the present invention.

[0063] Generally, the present disclosure is directed to a multichannel valve assembly for controlling one or more flows of fluids through a cassette of an automated cell engineering system while also reducing the risk to the cassette’s sterility. The improved sterility of the multichannel valve assembly, as described herein, allows for a single, shared and removable filter for the cassette, a neutral state that opens all pathways of the cassette, and / or an increased number of flow path control points for a set number of actuators. Accordingly, less filters may be used as compared to conventional automated cell engineering systems, leaving more space in the cassette for cell processing (e.g., transducing, transfecting, cell growth, etc.) and decreases an amount of sterilizing gas entry points for sterilizing the fluid pathways. To accomplish the improved sterility, the multichannel valve assembly comprises pinch valves configured to inhibit flow through one or more channels. That is, the pinch valves have a default closed state, thereby preventing fluid through the pinched conduits. Additionally, none of the channels or conduits are open to an external environment.

[0064] Moreover, the multichannel valve assembly may provide more precise control and greater flexibility in directing a flow of fluid through one or more conduits of the automated cell engineering system. For example, the multichannel valves may control flow through one or more channels and direct a flow of fluid through to one or more chambers, inlet ports, and / or outlet ports of the automated cell engineering system. In some implementations, the multichannel valve may control flow through two or three channels. Accordingly, actuation of one multichannel valve may control the flow through three conduits of the automated cell engineering system.

[0065] In some implementations, the multichannel valves may be fluidly connected to each other to increase the flexibility of controlling a flow of fluid through a fluid circuit defined by a cassette of the automated cell engineering system. For example, a first channel of a first multichannel valve assemblies may be fluidly connected to a second channel of a second multichannel valve assembly. Accordingly, actuation of a first multichannel valve or a second multichannel valve may control the flow of fluid through the first and second channels. An example fluid circuit is described in greater detail below.ATTORNEY DOCKET No. 0132-0338W01

[0066] Now referring to FIG. 1, an automated cell engineering system 1 having a cassette 10 is depicted in an open configuration. The automated cell engineering system 1 may be configured to perform biologic production steps such as, activating, transducing, expanding, concentrating, and / or harvesting of cells and / viruses. Example automated cell engineering systems for the automatic production of genetically modified immune cells, including CAR T cells, are described in U.S. Published Patent Application No. 2019 / 0169572 (the disclosure of which is incorporated by reference herein in its entirety), and are also called automated cell engineering system, COCOON™, or COCOON™ system herein. The cassette 10 of the automated cell engineering system 1 may be a single use device and disposed of after a cell engineering process.

[0067] FIG. 2 depicts a rear view of the cassette 10. The cassette 10 includes a cassette body 12 defining a plurality of valve seats 14. Each valve seat is configured to receive a valve assembly 100, 200. In the depicted embodiment, the cassette 10 includes a first valve assembly 100 according to a first embodiment, and a second valve assembly 200 according to a second embodiment. For clarity, the cassette 10 is depicted with two different embodiments of the valve assembly 100, 200 for illustration purposes. In some instances, the cassette 10 includes only first valve assemblies 100 or only second valve assemblies 200. Moreover, the automated cell engineering system 1 includes a plurality of actuators to actuate the valve assemblies 100, 200 of the cassette 10. That is, each actuator of the plurality of actuators corresponds to a valve assembly 100, 200. The actuators individually actuate corresponding valve assemblies 100, 200 when the cassette 10 is disposed in the automated cell engineering system 1.

[0068] FIGS. 3A-3C depict separate views of valve assembly 100. FIG. 3A depicts a perspective view of valve assembly 100. The valve assembly 100 includes a valve body 102, a plunger 110, a spring barrel 170, and a plurality of conduits 150. The spring barrel 170 is disposed on a first end 101 of the valve assembly 100 while the plunger 110 extends through the valve body 102 from a second end 103 of the valve assembly 100 towards the first end 101. The valve body 102 includes a pinch cap 104, an upper valve body 120, and a lower valve body 140. The plurality of conduits 150 (sometimes referred to herein as “tubing”) includes a first conduit 152 and second conduits 154. The tubing 150 extends through tube guides 1040 disposed in the pinch cap 104. The tube guides 1040 comprise through holes in the pinch cap 104 configured to receive the tubing 150. The first conduit 152 is disposed as a middle conduit between second conduits 154. The first conduit 152 and the second conduits 154 are each arranged to pass through the tube guides 1040 of the pinch cap 104.ATTORNEY DOCKET No. 0132-0338W01

[0069] Still referring to FIGS. 3A-3C, the plunger 110 includes a plunger shaft 112 and valve guide block 111 and a spring flange 116 (see FIG. 3C). The plunger 110 extends from the second end 103 towards the first end 101 where it is received by the spring barrel 170. The spring barrel 170 comprises a hollow cylinder having a lock groove 172 and retaining protrusions 174. The lock groove 172 is configured to receive a portion of the upper valve body 120. Meanwhile, the retaining protrusions 174 are configured to engage the spring flange 116 of the plunger 110.

[0070] FIG. 3B depicts a top, cut away view of the valve assembly 100 through the valve body 102 and pinch cap 104. The pinch cap 104 further includes guide walls 1042 extending towards the lower valve body 140. In the depicted embodiment, the pinch cap 104 includes four guide walls 1042 defining three channels for the tubing 150 and pinch bits 130. Two of the guide walls 1042 are formed as sidewalls of the pinch cap 104, while the other two guide walls 1042 are formed towards an interior of the pinch cap 104. Each of the guide walls 1042 also includes tab grooves 1044 for guiding the pinch bit 130 and protrusions 1046 configured to grip the tubing 150. Each conduit of the tubing 150 is arranged to pass through one of the tube guides 1040 at one end of the pinch cap 104, between two of the guide walls 1042 and protrusions 1046 and through the tube guides 1040 at the other end of the pinch cap 104. In this way, the pinch cap 104 maintains each conduit 152, 154 of the tubing 150 in alignment for engagement with one of the pinch bit 130.

[0071] FIG. 3C depicts an exploded view of the valve assembly 100. The pinch bit 130, the upper valve body 120, and lower valve body 140 are disposed around plunger 110. The spring barrel 170 is configured to receive the plunger 110 and a biasing element (not shown). For example, the biasing element may be disposed between the spring flange 116 of the plunger 110 and an internal end wall the spring barrel 170. In some implementations, the biasing element is a coil spring. One end of the coil spring may surround an end portion of the plunger 110 and engage the spring flange 116. Another end of the coil spring may pass through the spring barrel 170 towards the first end 101 and engage the internal end wall of the spring barrel 170.

[0072] The upper valve body 120 and lower valve body 140 are each configured to receive the pinch bit 130. During actuation of the valve assembly 100, the valve guide block 111 of the plunger 110 causes the pinch bit 130 to translate vertically in order to selectively open or close conduits of tubing 150. That is, the pinch valve bits 130 pinch or release the tubing 150 to close off or open the first conduit 152 and the second conduits 154 in response to horizontal movement of the valve guide block 111. For example, the pinch cap 104 provides a bearingATTORNEY DOCKET No. 0132-0338W01 surface against which the conduits of tubing 150 can be pressed against and pinched by the pinch bit 130.

[0073] Further details of the valve assembly 100 are depicted in FIG. 3C. The upper valve body 120 includes tubing guides 128 which align with the tube guides 1040 of the pinch cap 104 to assist in aligning the first conduit 152 and second conduits 154 of tubing 150 with the pinch bits 130. Both of the tube guides 1040 and tubing guides 128 are configured to approximately match the shape of the first conduit 152 and second conduits 154 of tubing 150 in order to create a snug fit of the valve assembly 100.

[0074] The upper valve body 120 further includes a locking tab 122 extending from a neck 123. The locking tab 122 and the neck 123 are configured to engage with the spring barrel 170. For example, the locking tab 122 engages the lock groove 172 and the neck 123 is configured to receive the retaining protrusions 174 of the spring barrel 170. The locking tab 122 has a diameter larger than the diameter of the spring barrel 170 and is inserted into the lock groove 172 of the spring barrel 170 via an opening in the lock groove 172. Meanwhile, the plunger 110 extends through the valve body 102 and into the spring barrel 170.

[0075] The plunger 110 is equipped with a spring flange 116 which has a diameter larger than the plunger shaft 112. The spring flange 116 provides a surface against which the biasing element in the spring barrel 170 can be compressed. The spring flange 116 is also equipped with notches which are sized correspondingly to the retaining protrusions 174 arranged at the edge of the spring barrel 170.

[0076] The retaining protrusions 174, which extend radially inwards from the spring barrel 170, are configured to engage with the neck 123 of the valve body 102 and / or the spring flange 116 towards the second end 103. The notches in spring flange 116 allow the spring flange 116 to bypass the retaining protrusions 174 and such that the plunger 110 can be inserted into the spring barrel 170.

[0077] In a first configuration (see FIG. 1 ID), the lock groove 172 and the locking tab 122 prevent the spring barrel 170 from releasing from the valve body 102. For example, the lock groove 172 engages the locking tab 122 and prevents the spring barrel 170 from rotating such that the locking tab 122 can exit the opening, thereby securing the spring barrel 170 and the plunger 110 to the valve body 102. In this configuration, the biasing element is compressed and biases the plunger 110 towards the second end 103. In a second configuration (see FIG. 11 A), the lock groove 172 is disengaged from the valve body 102. For example, in the second configuration, the spring barrel 170 is disposed towards the first end 101 as compared to when in the first configuration. Accordingly, the biasing element may be in an equilibrium state orATTORNEY DOCKET No. 0132-0338W01 in a less compressed state in the second configuration than in the first configuration. Said another way, the second configuration may place the valve assembly 100 in an intermediate or unactuated state. Further, in some implementations, the retaining protrusions 174 may engage the neck 123 to further engage the valve body 102 and prevent rotation and release of the spring barrel 170 in the second configuration.

[0078] Referring back to FIG. 3C, the lower valve body 140 includes a support 144 and a cradle 146 to support the lower side of the plunger 110 when the lower valve body 140 is placed together with the upper valve body 120. When the valve assembly 100 is assembled, the plunger 110 passes through both the valve body 102 and the spring barrel 170.

[0079] Referring to FIG. 4A and FIG. 4B, a front detail view of an example pinch bit 130 is depicted in FIG. 4A, and a side detail view of an example pinch bit 130 is depicted in FIG. 4B. The pinch bit 130 include a pinch bit head 132 at its upper end, a pinch bit foot 133 at its lower end, and a pinch bit shaft 134 extending therebetween. The pinch bit head 132 includes bit head tabs 138 which are configured to be slotted in the tab grooves 1044 of the pinch cap 104. That is, the bit head tabs 138 protrude outwards from the pinch bit head 132 of the pinch bit 130 to engage with the tab grooves 1044 of the pinch cap 104. The bit head tabs 138 are thus sized and shaped to correspond to the tab grooves 1044 of the pinch cap 104 to provide a smooth, guided, vertical motion of the pinch bit 130 and substantially prevent horizontal translation and rotational movement. The pinch bit foot 133 is configured to engage a lower surface of a corresponding valve guide 140A, 140B, 140C. That is, the lower surface of the valve guides 140 A, MOB, 140C apply a force to the pinch bit foot 133 to lower the pinch bit 130. ,

[0080] The pinch bit shaft 134 includes a first portion 134A having a first diameter and a second portion 134B having a second diameter. The first portion 134A of the pinch bit shaft 134 is sized to pass through pinch bit cylinder 124 of the upper valve body 120, shown in FIG. 5A, allowing the pinch bit 130 to move vertically through the upper valve body 120. The pinch bit cylinders 124 are holes provided in the upper valve body 120. Thus, the pinch bit 130 are configured to move up and down in the pinch bit cylinders 124 and guide walls 1042 in a piston-like motion. The pinch bit shaft 134 also includes a valve shoulder 136 having an angle 9, with respect to the horizontal, for slidingly engaging the valve guide block 111 of the plunger 110, such that longitudinal movement of the plunger 110 may be translated into vertical movement of the pinch bit 130. In some implementations, the angle 9 may be between 15 and 45 degrees, 10 and 30 degrees, 5 and 20 degrees, or 1 and 15 degrees. In someATTORNEY DOCKET No. 0132-0338W01 implementations, the angle 9 may be about 10 degrees, 15 degrees, 17 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, or 45 degrees.

[0081] FIG. 5A depicts an isometric view of the upper valve body 120. The upper valve body 120 includes opposing sidewalls 126 and a set of tubing guides 128 in each sidewall 126. The tubing guides 128 are each configured to receive a conduit of the tubing 150. The upper valve body 120 also includes pinch bit cylinders 124 between the sidewalls 126. Each pinch bit cylinder 124 is configured to receive and guide a pinch bit 130. In the depicted embodiment, the upper valve body 120 has three pinch bit cylinders 124. Each of the pinch bit cylinders 124 is aligned with one of the sets of tubing guides 128. The center pinch bit cylinder 124, corresponding to the center valve bit 130 and first conduit 152, may be offset from outer pinch bit cylinders 124 in a direction towards the first end 101 of the upper valve body 120.

[0082] The neck 123 of the upper valve body 120 further includes a neck groove 1230 and a bit stop 1232. The neck groove 1230 is sized and configured to receive the retaining protrusions 174 of spring barrel 170. The retaining protrusions 174 enter the neck groove 1230 via an opening at the edge of the neck 123. When the spring barrel 170 is rotated, retaining protrusions 174 become misaligned with the opening and are then held against the bit stop 1232, and these components are secured together. Thus, upon rotation of the spring barrel 170, the retaining protrusions 174 of the spring barrel 170 are secured against the bit stop 1232 of the neck 123 while the locking tab 122 of the neck 123 is secured against the lock groove 172 of the spring barrel 170. The dual locking action provides a secure engagement of the components.

[0083] Now referring to FIG. 5B, a perspective view of the lower valve body 140 is depicted. The lower valve body 140 includes receiving elements 142 as holes or grooves which are pinch bit 130 sized and shaped to receive each pinch bit foot 133 of the pinch bit 130. In some implementations, the pinch bit foot 133 may pass through the receiving elements 142. The receiving elements 142 are configured to align vertically with each of the pinch bit foot 133 and pinch bit cylinders 124, and provide additional clearance for each pinch bit 130 to be lowered into to avoid engagement of the tubing 150.

[0084] The lower valve body 140 also includes a neck groove 1230 and bit stop 1232 (not shown) disposed on a bottom surface of the cradle 146. When the upper valve body 120 and lower valve body 140 are placed together, neck groove 1230 and bit stop 1232 are disposed in a radially opposing manner to neck groove 1230 and bit stop 1232 of the neck 123. The neck groove 1230 and bit stop 1232 on the lower valve body 140 operate together with the neckATTORNEY DOCKET No. 0132-0338W01 groove 1230 and bit stop 1232 on the upper valve body 120 to secure the spring barrel 170 in the manner described above with reference to FIG. 5 A.

[0085] FIGS. 5C-5E depict various views of the pinch cap 104. In the depicted embodiment, the tab grooves 1044 of the guide walls 1042 can extend vertically along the length of the guide walls 1042 to accommodate the bit head tabs 138 of the pinch bit 130.

[0086] FIG. 6A depicts a side view of the valve assembly 100 showing first axis 20 and second axis 22. FIG. 6B depicts the plunger 110 and the pinch bit 130 without the valve body 102 or spring barrel 170. The first axis 20 extends along the longitudinal length of the plunger 110 and the spring barrel 170 from the first end 101 to the second end 103. Meanwhile, the second axis 22 is perpendicular to the first axis 20, and extends along a direction parallel to a longitudinal length of the pinch bit 130. During operation, translation of the plunger 110 along the first axis 20 causes one or more of the pinch bits 130 to translate along a direction parallel to the second axis 22.

[0087] FIG. 7A-7C depict a detail perspective view of the plunger 110 and pinch bit 130. The plunger 110 includes the plunger shaft 112 having a valve guide block 111 defining valve guides 114A, 114B, and 114C. Each of the valve guides 114A-114C define a center slot sized to accommodate the second portion 134B of a pinch bit 130A, 130B, 130C. The each of the valve guides 114A-114C also each include ramped portions 118A, 119A and flat portions 118B, 119B on each side of the center slot. The valve guides 114A-C are sized such that the ramped portions 118A, 119A and flat portions 118B, 119B abut the valve shoulders 136 of the pinch bit 130. The ramped portions 118A, 119A may also be angled to substantially match or be parallel to the angle 9 of the valve shoulder 136. In this way, axial movement of the plunger 110 causes either the ramped portions 118A, 119A or flat portions 118B, 119B to contact the valve shoulder 136 of the respective pinch bit 130. When the valve shoulder 136 of the pinch bit 130 slides along the flat portions 118B, 119B, the pinch bit 130 do not translate vertically. When the valve shoulder 136 of the pinch bit 130 slides along the ramped portions 118A, 119A the pinch bit 130 translate vertically up or down, depending on the direction of the ramped portions 118A, 119A and direction the plunger 110 is moved.

[0088] For example, axial movement of the plunger 110 towards the second end 103 will cause the ramped portions 118A of valve guides 114A and 114C to engage the valve shoulder 136 of respective pinch bits 130A and 130C (See FIG. 6B and 7 A). In this first state, the ramped portions 118A, 119A engage the valve shoulders 136 of the respective pinch bits 130A and 130C to vertically displace the respective valve bits 130A, 130C and pinch the respective second conduits 154 of tubing 150. Further, axial movement of the plunger 110 towards theATTORNEY DOCKET No. 0132-0338W01 first end 101 will allow the valve bits 130A and 130C to slide down the ramped portions 118A of valve guide 114A and 114C to return to a lowered position, thereby removing the pressure or force on the respective second conduits 154, allowing them to open to allow a flow therethrough.

[0089] Meanwhile, in the first state, the second pinch bit 13 OB rests on the lower flat portion 119B of the valve guide 114B, away from the first conduit 152 of the tubing 150. Axial movement of the plunger 110 towards the first end 101 of the valve assembly 100 causes the ramped portion 119A of valve guide 114B to engage the respective valve bit 130B and displace the second pinch bit 130B vertically upwards to pinch the respective first conduit 152. In this way, in certain embodiments, it is possible to close two conduits of tubing 150 while leaving one conduit of tubing 150 open, and vice versa. That is, second pinch bit 130B translates in an opposite direction as pinch bits 130A, 130C.

[0090] In some embodiments, each of the pinch bit 130 may be biased downwards in the vertical direction, away from tubing 150. In some implementations, the biasing may be performed by gravity, or a biasing element (e.g., a spring). Thus, the pinch bit 130 will not engage with and pinch tubing 150 unless the ramped portions 118A, 119A of the plunger 110 engage the corresponding valve shoulder 136 of the pinch bit 130.

[0091] FIGS. 8A and 8B depicts an axial view (FIG. 8A) and a side view (FIG. 8B) of the first state of the valve assembly 100. Referring to FIGS. 8A and 8B, but with continued reference to FIGS. 6B, 7A, and 7B, the valve assembly 100 is in the first state or default state. In the first state, the first pinch bit 130A aligned with valve guide 114A and the third pinch bit 130C aligned with valve guide 114C pinch closed second conduits 154 of tubing 150 while second pinch bit 130B within valve guide 114B does not engage the first conduit 152 of tubing 150, leaving it open. The first state may be the considered the default state of the valve assembly 100. In the first state, the biasing element disposed in the spring barrel 170 may bear against the spring flange 116 or first end 101 of the plunger 110 in a compressed state. That is, in the first state, the biassing element may bias the plunger 110 towards the second end 103. Accordingly, the plunger 110, biased toward the first state by the biasing element, causes the respective pinch bits 130A, 130C to engage and pinch off the corresponding second conduits 154. Meanwhile, the second pinch bit 130B rests on the flat portion 119B of the valve guide 114B and does not engage the first conduit 152.

[0092] Moving the plunger 110 towards first end 101, places the valve assembly 100 into a second state. Referring to FIGS 8C and 8D, an axial view (FIG. 8C) and a side view (FIG. 8D) of the valve assembly 100 is depicted in the second state or actuated state. In the secondATTORNEY DOCKET No. 0132-0338W01 state, pinch bit 130B is configured to close second conduit 154 of tubing 150. That is, the second pinch bit 130B engages and pinches closed the first conduit 152 of the tubing 150. Meanwhile the first pinch bit 130A and the third pinch bit 130C are configured to release the second conduits 154 of tubing 150, allowing those conduits 154 to open (e.g., allowing a flow of fluid therethrough).

[0093] In some implementations, when the valve assembly 100 is disposed in the cassette 10 and the cassette 10 is disposed in the automated engineering system 1, an actuator of the automated engineering system 1 may translate the plunger 110 towards the first end 101 of the valve assembly 100. For example, the actuator may apply a force on the second end 103. The force may be applied in a direction coaxial with, or parallel to, the first axis 20 and towards the first end 101. The force may be greater than the biasing force of the biasing spring in the spring barrel 170 to thereby translate the plunger 110 from the first state to the second state. When the actuator releases the plunger 110, the biasing element biases the plunger 110 back to the first state. That is, the biasing element may apply a biasing force to the spring flange 116, causing the plunger 110 to translate towards the second end 103. As noted above, the horizontal movement of the valve guide block 111 causes the pinch bits 130 to translate vertically.

[0094] FIG. 9 depicts a side view of the valve assembly 100 when the plunger 110 is actuated between the first state and the second state. In an embodiment, the plunger 110 travels a horizontal distance of about 8mm between the first state and the second state. Said another way, translating the plunger 110 approximately 8 mm causes the pinch bit 130 to translate vertically and pinch off or release the tubing 150. In some embodiments, the plunger 110 travels a horizontal distance of between 10 mm and 5 mm between the first state and the second state.

[0095] In the depicted embodiment, the flat portions 118B of valve guides 114A, 114C and flat portions 119C of valve guide 114B provide a constant height when the plunger 110 is actuated to or beyond a desired distance. Consequently, the corresponding pinch bit 130 remains at a constant height along these flat portions 118B, 119C. Thus, the pinch bit 130 cannot apply an excessive force to the tubing 150 nor the lower valve body 140 due to an over stroke of the plunger 110.

[0096] In some embodiments, the valve assembly 100 may have a third possible state which is a neutral state in which none of the conduits of tubing 150 are closed. FIG. 10 depicts a side view of the third state. The third state is between the first state and the second state. In the neutral state, the spring barrel 170 is unlocked from the neck 123. That is, the lock grooves 172 do not engage the locking tabs 122 and the spring barrel 170 is free to translate away fromATTORNEY DOCKET No. 0132-0338W01 the valve body 102. In this third state, the biasing element causes the spring barrel 170 to translate towards the first end 101, allowing the plunger 110 to float between the first state and second state. Consequently, the pinch bit 130 are prevented from engaging the tubing 150.

[0097] For example, each of the pinch bits 130 are raised slightly by the respective ramped portions 118A, 119A, but none of the pinch bits 130 are raised far enough or with enough force to engage, pinch, or close off the conduits of tubing 150, such that the cassette 10 may be sterilized and stored for a duration. For example, the open conduits 152, 154 allows a sterilization fluid (e.g., a liquid and / or a gas) to flow, unobstructed, through the tubing 150 to sterilize fluid pathways of the cassette 10 during a sterilization process. Further, keeping the valve assembly 100 in the third or neutral state during storage, or for a long duration, prevents plastic deformation of the tubing 150 by the pinch bits 130. For example, the cassette 10 may be sterilized and then shipped to a customer in the third state. The cassette 10 may sit on a shelf for an extended period of time. Keeping the valve assembly 100 in the third state prevents the pinch bits 130 from pinching the tubing 150 for an extended period. Pinching the tubing 150 for an extended period may cause plastic deformation of the tubing 150 which would in turn decrease a cross-sectional area of the first and second conduits 152,154. A decreased cross- sectional area would prevent, obstruct, or otherwise reduce a flow of fluid through the valve assembly 100 and cassette 10. Accordingly, the cassette 10 is shipped with the valve assembly 100 in the third or neutral state to prevent plastic deformation of the tubing 150 and the customer can set the valve assembly 100 into the first or default state when they are ready to use the cassette 10.

[0098] FIGS. 11 A-l ID depict a process for setting the valve assembly 100 to the default state, or first state, for use in the cassette 10. For example, the cassette 10 may be stored for a period of time from when the cassette 10 is sterilized and shipped to the user, to when cassette 10 is used in the automated cell engineering system 1. As noted above, keeping the valve assembly 100 in the neutral state or third state prevents deformation of the tubing 150.

[0099] When the cassette 10 is being prepared for use in the automated cell engineering system 1, the valve assembly 100 is placed in the first state or default state by a user. A first step, step 1 as shown in FIG. 11 A, includes aligning the locking tab 122 with the lock groove 172 and pressing the spring barrel 170 towards the valve body 102, thereby compressing the biasing element. The compressed biasing element causes the plunger 110 to translate towards the second end 103. A second step, step 2 as shown in Fig. 11B, includes rotating the spring barrel 170 clockwise, as viewed from first end 101, until the locking tab 122 is aligned with an end of the lock groove 172. The third and fourth steps, steps 3 and 4 as shown in FIGS. 11CATTORNEY DOCKET No. 0132-0338W01 and 1 ID, include translating the spring barrel 170 (either by pulling back on the spring barrel 170 or by force from the compressed biasing element) and engaging the locking tabs 122 of the valve body 102 with the lock groove 172 of the spring barrel 170. The compressed biasing element may bias the spring barrel 170 towards the first end 101 thereby causing the lock groove 172 to engage the locking tab 122 with a catch 176. Meanwhile, the spring barrel 170 and the compressed biasing element cooperate to bias the plunger 110 towards the second end 103 and the valve assembly 100 into the first state or default state. With all valve assemblies 100 set in the first state, the cassette 10 is ready for use in the automated cell engineering system 1.

[0100] Referring to FIGS. 12A, 12B and 12C depict a valve assembly 200 according to a second embodiment. FIG. 12A depicts a perspective view and FIG. 12B depicts a side view of the second embodiment of the valve assembly 200. FIG. 12C depicts a portion of the valve assembly 200. For clarity, reference numbers are carried over from the previously described embodiments and refer to substantially the same structures having substantially the same functions. Additionally, the automated cell engineering system 1 and cassette 10 have been omitted for illustrative purposes only. The valve assembly 200 includes a valve body 202 having a pinch cap 204 and a lower valve body 206 and a pinch bit 230 disposed therebetween (see FIGS. 12B, 12C and l3). The valve assembly 200 further includes a plunger 210 extending through the lower valve body 206 and a spring barrel 270 attached to the lower valve body 206 and configured to bias the plunger 210 towards a second end 103 of the valve assembly 200. A plurality of tubing 250 extends through the pinch cap 204. First conduits 252 of the plurality of tubing 250 extend above the pinch bit 230, while at least one second conduit 254 extends below a head 232 of the pinch bit 230.

[0101] The pinch bit 230, pinch cap 204 and lower valve body 206 cooperate to selectively pinch the first conduits 252 and the at least one second conduit 254 in response to translation of the plunger 210. The pinch bit 230 has an extended pinch bit head 232 which extends laterally to accommodate the diameter of at least two first conduits 252. In some instances, a width of the head 232 extends to the diameters of at least three parallel first conduits 252. The head 232 further includes pinch bit tabs 238 that extend laterally. The pinch bit tabs 238 cooperate with a groove or slot 2044 in the pinch cap 204 to vertically guide the pinch bit 230 when actuated. That is, slot 2044 is configured to receive and vertically guide the pinch bit tabs 238. When the pinch bit 230 is translated vertically upwards, the head 232 applies a pressure or force to the first conduits 252 and into the pinch cap 204. Accordingly, the pinch bit 230 and pinch cap 204 cooperate to pinch off, or close, the first conduits 252 in a first state.ATTORNEY DOCKET No. 0132-0338W01When the pinch bit 230 is translated vertically downwards to a second state, a bottom of the head 232 applies a pressure or force to the at least one second conduit 254 and into an upper surface 222 of the lower valve body 206. Accordingly, the pinch bit 230 and the lower valve body 206 cooperate to pinch off, or close, the at least one second conduit 254. Accordingly, the pinch bit 230 with the extended pinch bit head 232 is configured to close the first conduits 252 of tubing 250 when translated vertically upwards (e.g., first state or default state), and also configured to close at least one second conduit 254 when translated vertically downwards (e.g., second state or actuated state). In some implementations, the plunger 210 and pinch bit 230 may be disposed in a third state, or a neutral state, where neither the first conduits 252 nor the at least one second conduit 254 are pinched (similar to the third state of the first embodiment discussed above with respect to FIG. 10).

[0102] Now referring to FIG. 13, a perspective view of the pinch bit 230 and the plunger 210, in isolation, are depicted. Horizontal translation of the plunger 210 causes the pinch bit 230 to translate vertically. The plunger 210 is equipped with a guide rail 214 which is angled or askew with respect to a longitudinal axis of the plunger 210. A pinch bit shaft 234 of the pinch bit 230 includes an angled groove 236 configured to slidably receive the guide rail 214. The lower valve body 206 prevents the pinch bit 230 from translating horizontally. The guide rail 214 and the groove 236 cooperate to cause the pinch bit 230 to translate vertically in response to horizontal translation of the plunger 210. That is, as the plunger 210 translates along its longitudinal axis, the guide rail 214 slides along the angled groove 236 causing the pinch bit 230 to translate vertically. Accordingly, actuation of the plunger 210 towards the first end 101 translates the pinch bit 230 vertically downward via the guide rail 214. Meanwhile, translation of the plunger 210 towards the second end 103 translates the pinch bit 230 vertically upward via the guide rail 214. In some implementations, the guide rail 214 may be disposed on the pinch bit shaft 234 and the angled groove 236 may be disposed along the plunger 210.

[0103] FIG. 14A and 14B depict a schematic diagram of a fluid pathway 300 of the cassette 10 with the fluid connections of a plurality of the valve assemblies 100. The fluid pathway 300 includes a cell proliferation chamber 302, a dissolved oxygen sensor 304, a pH sensor 306, a satellite reagent bag 308, a fluid trap 310, a sterile air exchange filter 312, a fluid container 314, a weldable connection line 316, a peristatic pump 318, a mantic separator 320, weldable connection lines 324, 326, 328, 330, a fluidic bypass valve circuit 332, and a fluid reservoir, or cross flow reservoir, 334. Several pairs of valve assemblies are shown fluidly connected to each other. Open Conduits of the valve assemblies are shown as open circles. Meanwhile, closed conduits (e.g., conduits pinched off by the pinch bits) of the valve assemblies are shownATTORNEY DOCKET No. 0132-0338W01 as circles circumscribing an “x” . Each valve assembly includes three conduits of tubing A, B, and C. The three conduits of tubing of one valve assembly are fluidly connected with the three conduits of tubing of another valve assembly in the pair, in the manner depicted in FIG. 14B. The valve assemblies may be actuated to open or close a desired valve pair to induce a flow through the fluid pathway 300 in direction. That is, the flow of a fluid may flow in any desired direction by controlling the pair of valve assemblies and the peristatic pump 318.

[0104] FIG. 14B depicts a chart for determining the pathways when two valve assemblies are fluidly connected. Valve 1 (VI) and valve 2 (V2) each include three conduits of tubing 150 (A, B, and C). In VI, the conduits are arranged A-B-C, with B being the middle conduit and A and C being the outer conduits. In V2, the conduits are arranged B-A-C, with A being the middle conduit and B and C being the outer conduits. For each valve, the default state closes the outer conduits while leaving the center conduit open. The actuated state closes the middle conduit while leaving the outer conduits open. The tubing of VI is connected to the tubing of V2 in order to form connections of A-A, B-B, and C-C. In this arrangement, there are four possible results created, as depicted in the chart. When VI and V2 are both in the default state, as on the top left in FIG. 14B, all conduit pathways are closed. When VI is actuated, and V2 is in the default state, as on the top right, pathway A is open. When VI is in the default state and V2 is in the actuated state, as on the bottom left, pathway B is open. When VI is in the actuated state, and V2 is in the actuated state, as on the bottom right, pathway C is open. Accordingly, two connected valve assemblies, each having two states, are able to control up to three separate pathways

[0105] Referring back to FIG. 14A, two valve assemblies VI and V2 are paired, two valve assemblies V3 and V4 are paired, two valve assemblies V5 and V6 are paired, two valve assemblies V7 and V8 are paired, two valve assemblies V9 and VI 0 are paired, and two valve assemblies VI 1 and V12 are paired in the manner of VI and V2 in FIG. 14B. Some example pathways are highlighted. For example, when VI is in the actuated state, and V2 is in the actuated state, the Pathway A through the paired valve assemblies is open, allowed fluid to travel along the respective fluidic line represented by the schematic. Accordingly, the valve assemblies cooperate to control one or more flows of one or more fluids (including emulsions, and / or other substances carried by the fluid (e.g., cell cultures, vectors, proteins, molecules, etc.) through the cassette 10.Examples

[0106] Clause 1. A valve assembly for an automated cell engineering system comprising: a valve body; a plurality of conduits extending through the valve body; a plurality of pinch bitsATTORNEY DOCKET No. 0132-0338W01 configured to translate parallel to a first axis to selectively engage the conduits; and a plunger comprising: a plunger shaft; a first bit guide configured to actuate a first pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second bit guide configured to actuate a second pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first pinch bit and the second pinch bit in opposite directions.

[0107] Clause 2. The valve assembly of clause 1, wherein the first axis is substantially perpendicular to the plurality of conduits.

[0108] Clause 3. The valve assembly of clause 1, wherein the first pinch bit guide comprises a first ramp portion and a first horizontal portion, the first ramp portion configured to engage a first pinch bit shoulder of the first pinch bit.

[0109] Clause 4. The valve assembly of clause 3, wherein the second pinch bit guide comprises a second ramp portion and a second horizontal portion, the second ramp portion configured to engage a second pinch bit shoulder of the second pinch bit.

[0110] Clause 5. The valve assembly of clause 4, wherein the first ramp portion extends in a first ramp direction and the second ramp portion extends in a second ramp direction, wherein the first ramp direction and the second ramp direction are skew lines.

[0111] Clause 6. The valve assembly of clause 1, wherein the plunger further comprises a third pinch bit guide configured to actuate a third pinch bit of the plurality of pinch bits parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first pinch bit and the third pinch bit in parallel directions.

[0112] Clause 7. The valve assembly of clause 6, wherein the plunger is configured to actuate the valve assembly between a first state, a second state and a third state in response to translating along the first direction.

[0113] Clause 8. The valve assembly of clause 7, wherein the valve assembly further comprises a spring to bias the plunger along the first direction toward the first state.

[0114] Clause 9. The valve assembly of clause 7 or 8, wherein in the first state, the first pinch bit and the third pinch bit engage corresponding conduits of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduits.

[0115] Clause 10. The valve assembly of any one of clauses 7-9, wherein in the first state, the second pinch bit does not engage a corresponding conduit of the plurality of conduits.ATTORNEY DOCKET No. 0132-0338W01

[0116] Clause 11. The valve assembly of any one of clauses 7-10, wherein in the second state, the first pinch bit and the third pinch bit do not engage corresponding conduits of the plurality of conduits.

[0117] Clause 12. The valve assembly of any one of clauses 7-11, wherein in the second state, the second pinch bit engages a corresponding conduit of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduit.

[0118] Clause 13. The valve assembly of any one of clauses 7-12, wherein in the third state, the first pinch bit, the second pinch bit, and the third pinch bit do not engage the plurality of conduits.

[0119] Clause 14. The valve assembly of any one of clause 1-13, wherein the plurality of conduits comprise flexible tubing.

[0120] Clause 15. The valve assembly of any one of clause 1-14, wherein each pinch bit of the plurality of pinch bits is configured to engage a corresponding conduit by pinching the corresponding conduit.

[0121] Clause 16. A cassette for an automated cell engineering system comprising: a cassette body defining a plurality of valve seats; and a plurality of valve assemblies disposed in the plurality of valve seats, each valve assembly comprising: a valve body; a plurality of conduits extending through the valve body; a plurality of pinch bits configured to translate parallel to a first axis to selectively engage corresponding conduits of the plurality of conduits; and a plunger comprising: a plunger shaft; a first pinch bit guide configured to actuate a first pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second pinch bit guide configured to actuate a second pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to independently translate the first pinch bit and the second pinch bit.

[0122] Clause 17. The cassette of clause 16, wherein the plurality of valve assemblies includes: a first valve assembly having a first pinch bit configured to engage a first conduit of the plurality of conduits; and a second valve assembly having a second pinch bit configured to engage the first conduit.

[0123] Clause 18. The cassette of clause 17, wherein a second pinch bit of the first valve assembly is configured to engage a second conduit of the plurality of conduits and a first pinch bit of the second valve assembly is configured to engage the second conduit.ATTORNEY DOCKET No. 0132-0338W01

[0124] Clause 19. The cassette of any one of clauses 16-18, wherein each valve assembly of the plurality of valve assemblies further comprises a third pinch bit guide configured to actuate a third pinch bit of the plurality of pinch bits, wherein the third pinch bit of the first valve assembly is configured to engage a third conduit of the plurality of conduits and a third pinch bit of the second valve assembly is configured to engage the third conduit.

[0125] Clause 20. The cassette of any one of clauses 16-19, wherein the plurality of pinch bits are configured to selectively control fluid to flow through the plurality of conduits.

[0126] Clause 21. The cassette of any one of clauses 16-20, wherein the plurality of conduits comprise flexible tubing.

[0127] Clause 22. The cassette of any one of clauses 16-21, wherein each pinch bit of the plurality of pinch bits is configured to engage a corresponding conduit by pinching the conduit.

[0128] Clause 23. A method for conducting fluid through a cassette of an automated cell engineering system, the method comprising: translating, via an actuator, a plunger of a valve assembly along a plunger axis; translating, via the plunger, a first pinch bit and a second pinch bit perpendicularly to the plunger axis, wherein the first pinch bit translates independently from the second pinch bit; and opening, via the first pinch bit, a first conduit and simultaneously closing, via the second pinch bit, a second conduit.

[0129] Clause 24. The method of clause 23, further comprising translating a third pinch bit simultaneously and in parallel with the first pinch bit.

[0130] Clause 25. The method of any one of clauses 23-24, further comprising opening a third conduit, via a third pinch bit, simultaneously with the opening of the first conduit.

[0131] Clause 26. The method of any one of clauses 23-25, wherein closing a conduit comprises pinching the conduit with a corresponding pinch bit.

[0132] Clause 27. The method of any one of clauses 23-26, wherein opening a conduit comprises releasing the conduit with a corresponding pinch bit.

[0133] Each example embodiment disclosed herein has been included to present one or more different features. However, all disclosed example embodiments are designed to work together as part of a single larger system or method. This disclosure explicitly envisions compound embodiments that combine multiple previously-discussed features in different example embodiments into a single system or method.

[0134] While the invention has been illustrated and described in detail and with reference to specific embodiments thereof, it is nevertheless not intended to be limited to the details shown, since it will be apparent that various modifications and structural changes may be made therein without departing from the scope of the inventions and within the scope and range ofATTORNEY DOCKET No. 0132-0338W01 equivalents of the claims. In addition, various features from one of the embodiments may be incorporated into another of the embodiments. Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the scope of the disclosure as set forth in the following claims.

[0135] It is also to be understood that the automated cell engineering system 1, cassette 10, and valve assembly 100, 200 described herein, or portions thereof, may be fabricated from any suitable material or combination of materials, such as plastic, foamed plastic, metal, supple natural or synthetic materials including, but not limited to, cotton, elastomers, polyester, plastic, rubber, derivatives thereof, and combinations thereof. Suitable plastics may include high-density polyethylene (HDPE), low-density polyethylene (LDPE), polystyrene, acrylonitrile butadiene styrene (ABS), polycarbonate, polyethylene terephthalate (PET), polypropylene, ethylene-vinyl acetate (EVA), or the like. Suitable foamed plastics may include expanded or extruded polystyrene, expanded or extruded polypropylene, EVA foam, derivatives thereof, and combinations thereof.

[0136] Reference may be made to the spatial relationships between various components and to the spatial orientation of various aspects of components as depicted in the attached drawings. However, as will be recognized by those skilled in the art after a complete reading of the present disclosure, the devices, components, members, apparatuses, etc. described herein may be positioned in any desired orientation. Thus, the use of terms such as “above,” “below,” “upper,” “lower,” “top,” “bottom,” or other similar terms to describe a spatial relationship between various components or to describe the spatial orientation of aspects of such components, should be understood to describe a relative relationship between the components or a spatial orientation of aspects of such components, respectively, as the components described herein may be oriented in any desired direction. When used to describe a range of dimensions and / or other characteristics (e.g., time, pressure, temperature, distance, etc.) of an element, operations, conditions, etc., the phrase “between X and Y” represents a range that includes X and Y.

[0137] For example, it is to be understood that terms such as “left,” “right,” “top,” “bottom,” “front,” “rear,” “side,” “height,” “length,” “width,” “upper,” “lower,” “interior,” “exterior,” “inner,” “outer” and the like as may be used herein, merely describe points of reference and do not limit the present invention to any particular orientation or configuration. Further, the term “exemplary” is used herein to describe an example or illustration. AnyATTORNEY DOCKET No. 0132-0338W01 embodiment described herein as exemplary is not to be construed as a preferred or advantageous embodiment, but rather as one example or illustration of a possible embodiment.

[0138] Further, the present disclosure may repeat reference numerals and / or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and / or configurations discussed.

[0139] Similarly, when used herein, the term “comprises” and its derivations (such as “comprising,” etc.) should not be understood in an excluding sense, that is, these terms should not be interpreted as excluding the possibility that what is described and defined may include further elements, steps, etc. Meanwhile, when used herein, the term “approximately” and terms of its family (such as “approximate,” etc.) should be understood as indicating values very near to those which accompany the aforementioned term. For example, 10% of the given value. That is to say, a deviation within reasonable limits from an exact value should be accepted, because a skilled person in the art will understand that such a deviation from the values indicated is inevitable due to measurement inaccuracies, etc. The same applies to the terms “about” and “around” and “substantially”.

[0140] As used herein, unless expressly stated to the contrary, use of the phrase “at least one of,” “one or more of,” “and / or,” variations thereof, or the like are open-ended expressions that are both conjunctive and disjunctive in operation for any and all possible combination of the associated listed items. For example, each of the expressions “at least one of X, Y and Z,” “at least one of X, Y or Z,” “one or more of X, Y and Z,” “one or more of X, Y or Z” and “X, Y and / or Z” can mean any of the following: 1) X, but not Y and not Z; 2) Y, but not X and not Z; 3) Z, but not X and not Y; 4) X and Y, but not Z; 5) X and Z, but not Y; 6) Y and Z, but not X; or 7) X, Y, and Z.

[0141] Additionally, unless expressly stated to the contrary, the terms “first,” “second,” “third,” etc., are intended to distinguish the particular nouns they modify (e.g., element, condition, node, outlet, inlet, valve, module, activity, operation, etc.). Unless expressly stated to the contrary, the use of these terms is not intended to indicate any type of order, rank, importance, temporal sequence, or hierarchy of the modified noun. For example, “first X” and “second X” are intended to designate two “X” elements that are not necessarily limited by any order, rank, importance, temporal sequence, or hierarchy of the two elements. Further as referred to herein, “at least one of’ and “one or more of’ can be represented using the “(s)” nomenclature (e.g., one or more element(s)).

Claims

ATTORNEY DOCKET No. 0132-0338W01CLAIMS1. A valve assembly for an automated cell engineering system comprising: a valve body; a plurality of conduits extending through the valve body; a plurality of pinch bits configured to translate parallel to a first axis to selectively engage the conduits; and a plunger comprising: a plunger shaft; a first bit guide configured to actuate a first pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second bit guide configured to actuate a second pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first pinch bit and the second pinch bit in opposite directions.

2. The valve assembly of claim 1, wherein the first axis is substantially perpendicular to the plurality of conduits.

3. The valve assembly of claim 1, wherein the first pinch bit guide comprises a first ramp portion and a first horizontal portion, the first ramp portion configured to engage a first pinch bit shoulder of the first pinch bit.

4. The valve assembly of claim 3, wherein the second pinch bit guide comprises a second ramp portion and a second horizontal portion, the second ramp portion configured to engage a second pinch bit shoulder of the second pinch bit.

5. The valve assembly of claim 4, wherein the first ramp portion extends in a first ramp direction and the second ramp portion extends in a second ramp direction, wherein the first ramp direction and the second ramp direction are skew lines.

6. The valve assembly of claim 1, wherein the plunger further comprises a third pinch bit guide configured to actuate a third pinch bit of the plurality of pinch bits parallel to theATTORNEY DOCKET No. 0132-0338W01 first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to translate the first pinch bit and the third pinch bit in parallel directions.

7. The valve assembly of claim 6, wherein the plunger is configured to actuate the valve assembly between a first state, a second state and a third state in response to translating along the first direction.

8. The valve assembly of claim 7, wherein the valve assembly further comprises a spring to bias the plunger along the first direction toward the first state.

9. The valve assembly of claim 7 or 8, wherein in the first state, the first pinch bit and the third pinch bit engage corresponding conduits of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduits.

10. The valve assembly of any one of claims 7-9, wherein in the first state, the second pinch bit does not engage a corresponding conduit of the plurality of conduits.

11. The valve assembly of any one of claims 7-10, wherein in the second state, the first pinch bit and the third pinch bit do not engage corresponding conduits of the plurality of conduits.

12. The valve assembly of any one of claims 7-11, wherein in the second state, the second pinch bit engages a corresponding conduit of the plurality of conduits, thereby preventing fluid from flowing through the corresponding conduit.

13. The valve assembly of any one of claims 7-12, wherein in the third state, the first pinch bit, the second pinch bit, and the third pinch bit do not engage the plurality of conduits.

14. The valve assembly of any one of claim 1-13, wherein the plurality of conduits comprise flexible tubing.ATTORNEY DOCKET No. 0132-0338W0115. The valve assembly of any one of claim 1-14, wherein each pinch bit of the plurality of pinch bits is configured to engage a corresponding conduit by pinching the corresponding conduit.

16. A cassette for an automated cell engineering system comprising: a cassette body defining a plurality of valve seats; and a plurality of valve assemblies disposed in the plurality of valve seats, each valve assembly comprising: a valve body; a plurality of conduits extending through the valve body; a plurality of pinch bits configured to translate parallel to a first axis to selectively engage corresponding conduits of the plurality of conduits; and a plunger comprising: a plunger shaft; a first pinch bit guide configured to actuate a first pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along a first direction substantially perpendicular to the first axis; and a second pinch bit guide configured to actuate a second pinch bit of the plurality of pinch bits in a direction parallel to the first axis in response to translating the plunger shaft along the first direction, wherein the plunger is configured to independently translate the first pinch bit and the second pinch bit.

17. The cassette of claim 16, wherein the plurality of valve assemblies includes: a first valve assembly having a first pinch bit configured to engage a first conduit of the plurality of conduits; and a second valve assembly having a second pinch bit configured to engage the first conduit.

18. The cassette of claim 17, wherein a second pinch bit of the first valve assembly is configured to engage a second conduit of the plurality of conduits and a first pinch bit of the second valve assembly is configured to engage the second conduit.ATTORNEY DOCKET No. 0132-0338W0119. The cassette of any one of claims 16-18, wherein each valve assembly of the plurality of valve assemblies further comprises a third pinch bit guide configured to actuate a third pinch bit of the plurality of pinch bits, wherein the third pinch bit of the first valve assembly is configured to engage a third conduit of the plurality of conduits and a third pinch bit of the second valve assembly is configured to engage the third conduit.

20. The cassette of any one of claims 16-19, wherein the plurality of pinch bits are configured to selectively control fluid to flow through the plurality of conduits.

21. The cassette of any one of claims 16-20, wherein the plurality of conduits comprise flexible tubing.

22. The cassette of any one of claims 16-21, wherein each pinch bit of the plurality of pinch bits is configured to engage a corresponding conduit by pinching the conduit.

23. A method for conducting fluid through a cassette of an automated cell engineering system, the method comprising: translating, via an actuator, a plunger of a valve assembly along a plunger axis; translating, via the plunger, a first pinch bit and a second pinch bit perpendicularly to the plunger axis, wherein the first pinch bit translates independently from the second pinch bit; and opening, via the first pinch bit, a first conduit and simultaneously closing, via the second pinch bit, a second conduit.

24. The method of claim 23, further comprising translating a third pinch bit simultaneously and in parallel with the first pinch bit.

25. The method of any one of claims 23-24, further comprising opening a third conduit, via a third pinch bit, simultaneously with the opening of the first conduit.

26. The method of any one of claims 23-25, wherein closing a conduit comprises pinching the conduit with a corresponding pinch bit.ATTORNEY DOCKET No. 0132-0338W0127. The method of any one of claims 23-26, wherein opening a conduit comprises releasing the conduit with a corresponding pinch bit.

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