# US 2021/0197150 A1 · Scaleable inline buffer dilution scheme > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0197150 A1 - Document ID: US20210197150A1 - Status: Published application - Kind: A1 - Application number: 16/727,735 - Filed: 2019-12-26 - Published: 2021-07-01 - Earliest claimed: 2019-12-26 - Assignees: Asahi Kasei Bioprocess America, Inc. - Applicants: Asahi Kasei Bioprocess America, Inc. - Inventors: Michael D. Brandt - Web page: https://patentgrep.com/patent/US20210197150A1 ## CPC - B01F 35/2132: {Concentration, pH, pOH, p(ION) or oxygen-demand (B01F35/2133 takes precedence)} - G05D 21/02: characterised by the use of electric means - B01F 23/45: using flow mixing - B01F 23/483: {using water for diluting a liquid ingredient, obtaining a predetermined concentration or making an aqueous solution of a concentrate} - B01F 23/49: {Mixing systems, i.e. flow charts or diagrams} - B01F 25/64: of the centrifugal-pump type, i.e. turbo-mixers - B01F 35/2111: {Flow rate} - B01F 35/2133: {Electrical conductivity or dielectric constant of the mixture} - B01F 35/7176: {using pumps} - B01F 35/833: {Flow control by valves, e.g. opening intermittently} - G05D 11/138: {by sensing the concentration of the mixture, e.g. measuring pH value} - B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06) - G05D: SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES ## Abstract An inline buffer dilution system is provided that includes a first flow control valve fluidly connected to a supply of diluent liquid, second and third flow control valves fluidly connected to supplies of a first buffer and a second buffer, respectively, and a mixing pump fluidly connected to the first, second, and third flow control valves and configured to mix an amount of the diluent liquid, the first buffer, and the second buffer to produce a diluted buffer solution. The system further includes a backpressure control valve configured to generate a backpressure that promotes mixing within the mixing pump, and a controller configured to control the backpressure based on the amount of the diluent liquid, the first buffer, and the second buffer being mixed in the mixing pump, such that the mixing pump yields a minimum mixing threshold across a range of fluid flows. ## Claims ### Claim 1 An inline buffer dilution system, comprising: a first flow control valve adapted to communicate with a vessel comprising a supply of diluent liquid; a second flow control valve adapted to communicate with a first vessel comprising a supply of a first buffer; a third flow control valve adapted to communicate with a second vessel comprising a supply of a second buffer; a mixing pump fluidly connected to the first, second, and third flow control valves and configured to receive an amount of the diluent liquid, the first buffer, and the second buffer via the first, second, and third flow control valves, respectively, the mixing pump further configured to mix the amount of the diluent liquid, the first buffer, and the second buffer to produce a diluted buffer solution; a backpressure control valve arranged downstream of the mixing pump and configured to generate a backpressure that promotes mixing within the mixing pump; and a controller communicatively connected to the mixing pump and the backpressure control valve, the controller configured to control the backpressure generated by the backpressure control valve based on the amount of the diluent liquid, the first buffer, and the second buffer being mixed in the mixing pump, such that the mixing pump yields a minimum mixing threshold across a range of fluid flows. ### Claim 2 (depends on 1) The inline buffer dilution system of claim 1, wherein the backpressure control valve is configured to generate a first backpressure when the mixing pump mixes a first amount of the diluent liquid, the first buffer, and the second buffer, and wherein the backpressure control valve is configured to generate a second backpressure different from the first backpressure when the mixing pump mixes a second amount of the diluent liquid, the first buffer, and the second buffer. ### Claim 3 (depends on 2) The inline buffer dilution system of claim 2, wherein when the second amount is less than the first amount, the second backpressure is less than the first backpressure. ### Claim 4 (depends on 1) The inline buffer dilution system of claim 1, wherein the controller is configured to restrict a flow of the diluent liquid through the first flow control valve, thereby creating a negative pressure upstream of the mixing pump that drives the supply of the first buffer solution and the supply of the second buffer solution through the second flow control valve and the third flow control valve, respectively, and to the mixing pump. ### Claim 5 (depends on 1) The inline buffer dilution system of claim 1, further comprising an additional flow control valve arranged between the mixing pump and the backpressure control valve, the controller configured to control a pressure differential across the additional flow control valve. ### Claim 6 (depends on 1) The inline buffer dilution system of claim 1, further comprising the first vessel comprising the supply of the first buffer and the second vessel comprising the supply of the second buffer, wherein each of the first vessel and the second vessel is pressurized using only atmospheric pressure. ### Claim 7 (depends on 1) The inline buffer dilution system of claim 1, further comprising a conductivity sensor arranged between the mixing pump and the backpressure control valve, the conductivity sensor configured to detect the conductivity of the diluted buffer solution produced by the mixing pump. ### Claim 8 (depends on 1) The inline buffer dilution system of claim 1, further comprising a pH sensor arranged between the mixing pump and the backpressure control valve, the pH sensor configured to detect the pH of the diluted buffer solution produced by the mixing pump. ### Claim 9 (depends on 1) The inline buffer dilution system of claim 1, further comprising a first flowmeter fluidly coupled to the second flow control valve and a second flowmeter fluidly coupled to the third flow control valve, the controller communicatively connected to the first and second flowmeters and configured to obtain from the first and second flowmeters data indicative of the fluid flowing through the second and third flow control valves, respectively. ### Claim 10 An inline buffer dilution system, comprising: a vessel comprising a supply of diluent liquid; a first vessel comprising a supply of a first buffer, the first vessel pressurized using only atmospheric pressure; a second vessel comprising a supply of a second buffer, the second vessel pressurized using only atmospheric pressure; a first flow control valve arranged downstream of and configured to communicate with the supply of diluent liquid; a second flow control valve arranged downstream of and configured to communicate with the first vessel comprising the supply of the first buffer; a third flow control valve arranged downstream of and configured to communicate with the second vessel comprising the supply of the second buffer; a mixing pump fluidly connected to the first, second, and third flow control valves and configured to receive an amount of the diluent liquid, the first buffer, and the second buffer via the first, second, and third flow control valves, respectively, the mixing pump further configured to mix the amount of the diluent liquid, the first buffer, and the second buffer to produce a diluted buffer solution; a backpressure control valve arranged downstream of the mixing pump and configured to generate a backpressure that promotes mixing within the mixing pump; and a controller communicatively connected to the mixing pump and the backpressure control valve, the controller configured to control the backpressure generated by the backpressure control valve based on the amount of the diluent liquid, the first buffer, and the second buffer being mixed in the mixing pump, such that the mixing pump yields a minimum mixing threshold across a range of fluid flows. ### Claim 11 (depends on 10) The inline buffer dilution system of claim 10, wherein the backpressure control valve is configured to generate a first backpressure when the mixing pump mixes a first amount of the diluent liquid, the first buffer, and the second buffer, and wherein the backpressure control valve is configured to generate a second backpressure different from the first backpressure when the mixing pump mixes a second amount of the diluent liquid, the first buffer, and the second buffer. ### Claim 12 (depends on 11) The inline buffer dilution system of claim 11, wherein when the second amount is less than the first amount, the second backpressure is less than the first backpressure. ### Claim 13 (depends on 10) The inline buffer dilution system of claim 10, wherein the controller is configured to restrict a flow of the diluent liquid through the first flow control valve, thereby creating a negative pressure upstream of the mixing pump that drives the supply of the first buffer solution and the supply of the second buffer solution through the second flow control valve and the third flow control valve, respectively, and to the mixing pump. ### Claim 14 (depends on 10) The inline buffer dilution system of claim 10, further comprising an additional flow control valve arranged between the mixing pump and the backpressure control valve, the controller configured to control a pressure differential across the additional flow control valve. ### Claim 15 (depends on 10) The inline buffer dilution system of claim 10, further comprising a conductivity sensor arranged between the mixing pump and the backpressure control valve, the conductivity sensor configured to detect the conductivity of the diluted buffer solution produced by the mixing pump. ### Claim 16 (depends on 10) The inline buffer dilution system of claim 10, further comprising a pH sensor arranged between the mixing pump and the backpressure control valve, the pH sensor configured to detect the pH of the diluted buffer solution produced by the mixing pump. ### Claim 17 (depends on 10) The inline buffer dilution system of claim 10, wherein the first vessel comprises a first container housing the supply of the first buffer and the second vessel comprises a second container housing the supply of the second buffer, and wherein each of the first and second containers is made from a disposable material. ### Claim 18 (depends on 17) The inline buffer dilution system of claim 17, wherein the disposable material comprises a gamma stable plastic material. ### Claim 19 A method of producing a diluted buffer solution across a range of fluid flows, comprising: providing a first flow control valve adapted to communicate with a vessel comprising a supply of diluent liquid, a second flow control valve adapted to communicate with a first vessel comprising a supply of a first buffer, and a third flow control valve adapted to communicate with a second vessel comprising a supply of a second buffer; directing an amount of the diluent liquid, the first buffer, and the second buffer to a mixing pump; mixing the amount of the diluent liquid, the first buffer, and the second buffer in the mixing pump, thereby producing a diluted buffer solution; generating, via a backpressure control valve arranged downstream of the mixing pump, a backpressure that promotes mixing within the mixing pump; and controlling, via a controller communicatively connected to the mixing pump and the backpressure control valve, the backpressure generated by the backpressure control valve based on the amount of the diluent liquid, the first buffer, and the second buffer being mixed in the mixing pump. ### Claim 20 (depends on 19) The method of claim 19, wherein the controlling comprises decreasing the backpressure generated by the backpressure control valve when the amount of the diluent liquid, the first buffer, and the second buffer being mixed in the mixing pump decreases.