# US 2024/0200007 A1 · Combinatorial fluid switch for use in automated cell engineering systems > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0200007 A1 - Document ID: US20240200007A1 - Status: Published application - Kind: A1 - Application number: 18/554,768 - Filed: 2022-04-11 - Published: 2024-06-20 - Earliest claimed: 2021-04-12 - Applicants: Octane Biotech Inc. - Inventors: Peter SZARAZ; Nuala TRAINOR - Web page: https://patentgrep.com/patent/US20240200007A1 ## CPC - C12M 23/40: {Manifolds; Distribution pieces (fluid transfer means B01L3/563)} - C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)} - C12M 41/48: {Automatic or computerized control (automatic analysis G01N35/00)} - F16K 99/0015: {Diaphragm or membrane valves} - F16K 99/0028: {Valves having multiple inlets or outlets} - F16K 2099/0084: {Chemistry or biology, e.g. "lab-on-a-chip" technology} - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} - F16K: VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING {(devices for emptying and evacuating the excess liquid in valves or conduits F16L55/07)} ## Abstract The present disclosure provides combinatorial fluid switches that allow for the selection of a single fluid flow-path, while controlling multiple flow-paths. The combinatorial fluid switches can be used in various biological systems and processes, included automated cell engineering systems. ## Claims ### Claim 1 A combinatorial fluid switch for controlling fluid flow through a plurality of fluid flow-paths, comprising: (a) a plurality of fluid inputs; (b) a first two-position valve having individual fluid flow-paths, through which fluids from the plurality of fluid inputs are guided; (c) a second two-position valve having individual fluid flow-paths, through which fluids from the plurality of fluid inputs are guided; and (d) a plurality of fluid outputs, wherein the combinatorial fluid switch is configured to allow: fluid flow from a first fluid input to a first fluid output when the first two-position valve is in an open position and the second two-position valve is in an open position; fluid flow from a second fluid input to a second fluid output when the first two-position valve is in a closed position and the second two-position valve is in an open position; fluid flow from a third fluid input to a third fluid output when the first two-position valve is in an open position and the second two-position valve is in a closed position; and fluid flow from a fourth fluid input to a fourth fluid output when the first two-position valve is in a closed position and the second two-position valve is in a closed position. ### Claim 2 (depends on 1) The combinatorial fluid switch of claim 1, wherein the fluid inputs comprise tubing. ### Claim 3 (depends on 1, 2) The combinatorial fluid switch of claim 1 or claim 2, wherein the fluid flow-paths comprise tubing. ### Claim 4 (depends on 1, 2, 3) The combinatorial fluid switch of any one of claims 1-3, wherein the two-position valves are trumpet valves. ### Claim 5 (depends on 1, 2, 3, 4) The combinatorial fluid switch of any one of claims 1-4, wherein the fluid outputs comprise tubing. ### Claim 6 (depends on 1, 2, 3, 4, 5) The combinatorial fluid switch of any one of claims 1-5, wherein the fluid inputs, the fluid flow-paths and the fluid outputs consist of at least four tubing lines. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The combinatorial fluid switch of any one of claims 1-6, wherein each of the fluid inputs are fed from a single fluid source. ### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7) The combinatorial fluid switch of any one of claims 1-7, wherein fluids within the fluid flow paths are not allowed to mix. ### Claim 9 A combinatorial fluid switch for controlling fluid flow through at least four fluid flow-paths, comprising: (a) a first, a second, a third and a fourth fluid inputs; (b) a first two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; (c) a second two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; and (d) a first, a second, a third and a fourth fluid outputs, wherein the combinatorial fluid switch is configured to allow: fluid flow from the first fluid input to the first fluid output when the first two-position valve is in an open position and the second two-position valve is in an open position; fluid flow from the second fluid input to the second fluid output when the first two-position valve is in a closed position and the second two-position valve is in an open position; fluid flow from the third fluid input to the third fluid output when the first two-position valve is in an open position and the second two-position valve is in a closed position; and fluid flow from the fourth fluid input to the fourth fluid output when the first two-position valve is in a closed position and the second two-position valve is in a closed position. ### Claim 10 (depends on 9) The combinatorial fluid switch of claim 9, wherein the fluid inputs comprise tubing. ### Claim 11 (depends on 9, 10) The combinatorial fluid switch of claim 9 or claim 10, wherein the fluid flow-paths comprise tubing. ### Claim 12 (depends on 9, 10, 11) The combinatorial fluid switch of any one of claims 9-11, wherein the two-position valves are trumpet valves. ### Claim 13 (depends on 9, 10, 11, 12) The combinatorial fluid switch of any one of claims 9-12, wherein the fluid outputs comprise tubing. ### Claim 14 (depends on 9, 10, 11, 12, 13) The combinatorial fluid switch of any one of claims 9-13, wherein the fluid inputs, the fluid flow-paths and the fluid outputs consist of four tubing lines. ### Claim 15 (depends on 9, 10, 11, 12, 13, 14) The combinatorial fluid switch of any one of claims 9-14, wherein each of the fluid inputs are fed from a single fluid source. ### Claim 16 A system for controlling fluid flow through at least sixteen fluid flow-paths, comprising: (a) a first combinatorial fluid switch comprising: i. a first, a second, a third and a fourth fluid inputs; ii. a first two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; iii. a second two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; and iv. a first, a second, a third and a fourth fluid outputs, wherein the first combinatorial fluid switch is configured to allow: fluid flow from the first fluid input to the first fluid output when the first two-position valve is in an open position and the second two-position valve is in an open position; fluid flow from the second fluid input to the second fluid output when the first two-position valve is in a closed position and the second two-position valve is in an open position; fluid flow from the third fluid input to the third fluid output when the first two-position valve is in an open position and the second two-position valve is in a closed position; and fluid flow from the fourth fluid input to the fourth fluid output when the first two-position valve is in a closed position and the second two-position valve is in a closed position; and (b) a second combinatorial fluid switch fluidly connected to the first combinatorial fluid switch, the second combinatorial fluid switch comprising: i. a fifth, a sixth, a seventh and an eighth fluid inputs; ii. a third two-position valve having four fluid flow-paths, through which fluids from the fifth, sixth, seventh and eighth fluid inputs are guided; iii. a fourth two-position valve having four fluid flow-paths, through which fluids from the fifth, sixth, seventh and eighth fluid inputs are guided; and iv. a fifth, a sixth, a seventh and an eighth fluid outputs, wherein the second combinatorial fluid switch configured to allow: fluid flow from the fifth fluid input to the fifth fluid output when the third two-position valve is in an open position and the fourth two-position valve is in an open position; fluid flow from the sixth fluid input to the sixth fluid output when the third two-position valve is in a closed position and the third two-position valve is in an open position; fluid flow from the seventh fluid input to the seventh fluid output when the third two-position valve is in an open position and the fourth two-position valve is in a closed position; and fluid flow from the eighth fluid input to the eighth fluid output when the third two-position valve is in a closed position and the fourth two-position valve is in a closed position. ### Claim 17 A system for controlling fluid flow through at least sixteen fluid flow-paths, comprising: (a) a plurality of combinatorial fluid switches, each combinatorial fluid switch comprising: i. a first, a second, a third and a fourth fluid inputs; ii. a first two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; iii. a second two-position valve having four fluid flow-paths, through which fluids from the first, second, third and fourth fluid inputs are guided; and iv. a first, a second, a third and a fourth fluid outputs, wherein the first combinatorial fluid switch is configured to allow: fluid flow from the first fluid input to the first fluid output when the first two-position valve is in an open position and the second two-position valve is in an open position; fluid flow from the second fluid input to the second fluid output when the first two-position valve is in a closed position and the second two-position valve is in an open position; fluid flow from the third fluid input to the third fluid output when the first two-position valve is in an open position and the second two-position valve is in a closed position; and fluid flow from the fourth fluid input to the fourth fluid output when the first two-position valve is in a closed position and the second two-position valve is in a closed position. ### Claim 18 (depends on 16, 17) The system of claim 16 or claim 17, wherein each of the combinatorial fluid switches is fluidly connected to each other. ### Claim 19 (depends on 16, 17) The system of claim 16 or claim 17, comprising 4 or more combinatorial fluid switches. ### Claim 20 (depends on 16, 17, 18, 19) The system of any one of claims 16-19, wherein the fluid inputs comprise tubing. ### Claim 21 (depends on 16, 17, 18, 19, 20) The system of any one of claims 16-20, wherein the fluid flow-paths comprise tubing. ### Claim 22 (depends on 16, 17, 18, 19, 20, 21) The system of any one of claims 16-21, wherein each of the valves are trumpet valves. ### Claim 23 (depends on 16, 17, 18, 19, 20, 21, 22) The system of any one of claims 16-22, wherein the fluid outputs comprise tubing. ### Claim 24 (depends on 16, 17, 18, 19, 20, 21, 22, 23) The system of any one of claims 16-23, wherein the fluid inputs, the fluid flow-paths and the fluid outputs consist of at least eight tubing lines. ### Claim 25 (depends on 1) An automated biologic production system, comprising: (a) an enclosable housing; (b) a cassette contained within the enclosable housing, the cassette comprising: i. a cell culture chamber ii. a combinatorial fluid switch of claim 1; iii. a pumping system fluidly connected to the cell culture chamber and the combinatorial switch; iv. one or more of a temperature sensor, a pH sensor, a glucose sensor, a lactose sensor, an oxygen sensor, a carbon dioxide sensor, and an optical density sensor; and v. mechanisms to automatically adjust one or more of a temperature, a pH level, a glucose level, a lactose level, an oxygen level, a carbon dioxide level, and an optical density. ### Claim 26 (depends on 8, 9) An automated biologic production system, comprising: (a) an enclosable housing; (b) a cassette contained within the enclosable housing, the cassette comprising: i. a cell culture chamber; ii. a system of claim 8 or claim 9; iii. a pumping system fluidly connected to the cell culture chamber and the system; iv. one or more of a temperature sensor, a pH sensor, a glucose sensor, a lactose sensor, an oxygen sensor, a carbon dioxide sensor, and an optical density sensor; and v. mechanisms to automatically adjust one or more of a temperature, a pH level, a glucose level, a lactose level, an oxygen level, a carbon dioxide level, and an optical density. ### Claim 27 (depends on 25, 26) The automated biologic production system of claim 25 or claim 26, configured to produce cells. ### Claim 28 (depends on 25, 26, 27) The automated biologic production system of any one of claims 25-27, further comprising a magnetic cell separation device. ### Claim 29 (depends on 25, 26, 27, 28) The automated biologic production system of any one of claims 25-28, further comprising an electroporation device. ### Claim 30 (depends on 25, 26, 27, 28, 29) The automated biologic production system of any one of claims 25-29, wherein the automated biologic production system includes at least 16 fluid flow-paths. ### Claim 31 (depends on 25, 26, 27, 28, 29, 30) The automated biologic production system of any one of claims 25-30, wherein the automated biologic production system includes at least 20 fluid flow-paths. ### Claim 32 A combinatorial fluid switch, comprising: (a) a housing having two opposing sides, each side having four openings passing therethrough; and (b) two, two-position valves disposed within the housing, each valve having four openings passing therethrough, wherein the openings in the sides and the openings in the two-position valves are configured to receive tubing therethrough, so as to create four flow-paths within the combinatorial fluid switch, and wherein the two-position valves are moveable within the housing to allow fluid flow through only one flow-path at a time. ### Claim 33 (depends on 32) The combinatorial fluid switch of claim 32, wherein the two-position valves are slidable within the housing. ### Claim 34 (depends on 32) The combinatorial fluid switch of claim 32, wherein the two-position valves are rotatable within the housing. ### Claim 35 (depends on 32, 33, 34) The combinatorial fluid switch of any one of claims 32-34, further comprising four tubing lines passing through the four openings in the sides and the four openings in the two-position valves. ### Claim 36 A combinatorial fluid switch, comprising: (a) a support base comprising two raised portions and two recessed portions, the two raised portions comprising a plurality of partitions extending above the support base configured to allow tubing to pass therethrough so as to create four fluid flow-paths, the two recessed portions each comprising four stationary compression members extending above the support base; (b) two, two-position valves having openings to allow the stationary compression members to pass through, the valves further comprising four movable compression members configured to compress against a complementary, stationary compression member on the support base so as to constrict a tubing between the movable compression member and the complementary, stationary compression member, wherein the two-position valves are configured to slide along the support base and allow fluid flow through only one flow-path at a time. ### Claim 37 (depends on 36) The combinatorial fluid switch of claim 36, wherein the two, two-position valves are flat valves that slide within the two recessed portions of the support base. ### Claim 38 (depends on 36, 37) The combinatorial fluid switch of claim 36 or claim 37, further comprising four tubing lines passing through the partitions, the stationary compression members and the movable compression members. ### Claim 39 A combinatorial fluid switch, comprising: (a) at least three, stationary compression members; (b) a first two-position valve having two movable compression members integrated into the valve; and (c) a second two-position valve having three movable compression members integrated into the valve, wherein the movable compression members of the first and second two-position valves are configured to compress against a complementary, stationary compression member so as to constrict a tubing between the movable compression member and the complementary, stational compression member, wherein the two-position valves are configured to slide and allow fluid flow through one flow-path at a time. ### Claim 40 (depends on 39) The combinatorial fluid switch of claim 39, wherein the stationary compression modules are disposed within a housing. ### Claim 41 (depends on 39, 40) The combinatorial fluid switch of claim 39 or claim 40, wherein the two-position valves are trumpet valves ### Claim 42 (depends on 39, 40, 41) The combinatorial fluid switch of any one of claims 39-41, further comprising four tubing lines passing through the stationary compression members and the movable compression members, to provide four fluid flow-paths. ### Claim 43 A combinatorial fluid switch for controlling fluid flow through a plurality of fluid flow-paths, comprising: (a) a plurality of fluid inputs; (b) a first control valve, through which fluids from the plurality of fluid inputs are guided; (c) a second control valve having individual fluid flow-paths, through which fluids from the plurality of fluid inputs are guided; and (d) a plurality of fluid outputs, wherein the combinatorial fluid switch is configured to allow fluid flow through a designated combination of fluid inputs and fluid outputs. ### Claim 44 A method for controlling fluid flow within a closed, cell engineering system, comprising: (a) providing a plurality of fluid inputs; (b) providing a plurality of fluid outputs; (c) providing a plurality of flow-paths connecting the fluid inputs to the fluid outputs; (d) providing a plurality of valves controlling the flow within the flow-paths, thereby controlling the direction, speed, duration and/or interval of fluid flow within the flow-paths.