The invention relates to a method of transferring a microbial bioprocess from a multi-use bioreactor (1) to a single-use bioreactor (2), wherein the source bioprocess is a batch or fed-batch microbial bioprocess and the source bioprocess arrangement (3) comprises a source bioreactor (5) with a stirrer and the source bioreactor (5) is the multi-use bioreactor (1) which has at least 1000 L production volume of a microbial culture producing a maximum heat of at least 25,000 W and/or the stirrer of the source bioreactor (5) is driven with a maximum torque of at least 120 Nm, wherein the target bioprocess is a continuous microbial bioprocess and the target bioprocess arrangement (4) comprises a target bioreactor (6) and the target bioreactor (6) is the single-use bioreactor (2) which has a production volume of a microbial culture of at most 50 % of the production volume of the source bioreactor (5) and of at most 800 L, the microbial culture of the target bioreactor (6) produces a maximum heat of at most 20,000 W during the target bioprocess and/or the target bioreactor (6) comprises a stirrer driven with a maximum torque of at most 100 Nm, wherein an average amount of the bioproduct produced per time of performance of the target bioprocess by the target bioreactor (6) is at least 90 %, preferably at least 100 %, of an average amount of the bioproduct produced per time of performance of the source bioprocess by the source bioreactor (5).
Described and illustrated is a air vent valve (1) for the use in a (bio)pharmaceutical process, comprising: a first housing (2), a first interior chamber (5) arranged within the first housing, a first inlet (3) for conveying air and/or liquid medium to the first interior chamber (5), a first outlet (4) for conveying air away from the first interior chamber (5), and a first floating member (6) for sealing the first outlet (4), wherein the first inlet (3) and the first outlet (3) are respectively connected via a fluidic connection with the first interior chamber (5), and wherein the first floating member (6) is arranged movable within the first interior chamber (5). To improve air vent valves, preferably to provide a less complex air vent valve, the describe air vent valve it is proposed.
Depicted and described is a Filter module (1) for the tangential flow filtration of a feed medium, comprising: a, preferably cassette-shaped, housing (2), one or more hollow fibers (8) for separating a feed medium into a retentate and a permeate, wherein the housing (2) has one or more transverse extension axes (TEA) and/or one or more longitudinal extension axes (LEA), wherein one or more conduits (9) are arranged in the housing (2), wherein the one or more hollow fibers (8) are arranged in the one or more conduits (9). In order to provide a filter module (1) which allows for the use of hollow fibers (8) with a set, preferably standardized, length while allowing for an individual arrangement of inlets and outlets of the filter module (1) it is proposed that the one or more hollow fibers (8) are at least in sections bent around the one or more transverse extension axes (TEA) and/or the one or more hollow fibers (8) are at least in sections bent around the one or more longitudinal extension axes (LEA).
4.
FILTRATION DEVICE FOR FILTERING A MEDIUM, METHOD OF ASSEMBLING A FILTRATION DEVICE, AND METHOD OF CONDUCTING A FILTRATION PROCESS
A filtration device (10) for filtering a medium, in particular a small-scale filtration device for the production and/or processing of biopharmaceuticals, comprises: a top cover (12) having an unfiltrate inlet (14) and a bottom cover (16) having a filtrate outlet (18), and a plurality of filter supports (28), arranged as a stack between the top cover (12) and the bottom cover (16) along a vertical axis. Each filter support (28) is provided with a flat filter (24), especially a membrane. Each flat filter (24) is sealed to the filter support (28) with a filtrate side facing the respective filter support (28) and an unfiltrate side facing away from the respective filter support (28). The filtration device further comprises one or more intermediate elements (30), preferably one or more intermediate plates. A first intermediate element (30) is arranged between the stacked filter supports (28), dividing the filter supports (28) into an upper group (32) above the intermediate element (30) and a lower group (34) below the intermediate element (30). The first distribution flow paths lead from the unfiltrate inlet (14) to all unfiltrate sides of the flat filters (24) of the upper group (32). The first intermediate element (30) has a structure that blocks the first distribution flow paths from reaching the unfiltrate sides of the flat filters (24) of the lower group (34) and provides first collecting paths for collecting the medium that has passed through the flat filters (24) of the upper group (32). Second distribution flow paths lead from the first collecting paths to all unfiltrate sides of the flat filter(s) (24) of the lower group (34). Second collecting paths collect the medium that has passed through the flat filter(s) (24) of the lower group (34).
B01D 29/05 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with flat filtering elements supported
B01D 29/41 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with hollow discs side by side on, or around, one or more tubes, e.g. of the leaf type mounted transversely on the tube
B01D 29/56 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with multiple filtering elements, characterised by their mutual disposition in series connection
B01D 29/58 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with multiple filtering elements, characterised by their mutual disposition in series connection arranged concentrically or coaxially
A measuring cell unit (16) for a bioprocess system is shown, in particular for a biopharma process, comprising a flow pipe unit (28) with a first connection end (30) having an inlet channel (34), a second connection end (32) having an outlet channel (36) and a measuring chamber (38) between the inlet and the outlet channels (34, 36). The first and second connection ends (30, 32) are configured to connect the measuring cell unit (16) into the bioprocess system. Together, the inlet channel (34), the measuring chamber (38) and the outlet channel (36) define portions of a flow duct (40) through the measuring cell unit (16). Further, the flow pipe unit (16) comprises a sideward sensor insert hole (42) opening into the measuring chamber (38) such that a measuring sensor (26) can be inserted. The flow duct (40) further comprises a transitional portion (44) along which a cross-sectional area of the flow duct (40) increases from the inlet channel (34) towards the measuring chamber (38). Additionally, the measuring cell unit (16) comprises at least one flow deflection arm (46) extending into the transitional portion (44) and deflecting a fluid flowing through the flow duct (40). Further, a bioprocess system and a method for displacing a first fluid by a second fluid are shown.
The invention relates to a method for adjusting the pH of a process liquid in a continuous process, comprising (a.) providing the process liquid in a first volume flow having a first flow rate, (b.) providing at least one treatment liquid in a second volume flow having a second flow rate, (c.) mixing the at least one treatment liquid with the process liquid to produce a pH-adjusted process liquid, wherein the second flow rate is composed of a predetermined portion and a variable portion, and wherein the variable portion is controlled based on at least one liquid parameter of the pH-adjusted process liquid. The method is characterized in that the predetermined portion is determined based on the pH value and/or the UV absorbance and/or the conductivity of the process liquid.
The present invention relates to a flow system for the continuous treatment of a process liquid. The flow system comprises a recirculation loop comprising a compensation tank having an inlet and an outlet, a circulation line connecting the inlet and outlet of the compensation tank to one another, at least one sensor for determining at least one liquid parameter, supply lines for the process liquid and at least one treatment liquid which are connected to the recirculation loop, and discharge lines for treated process liquid and waste streams connected to the recirculation loop.
The present invention relates to a method for validating the ability of a test filter unit to produce a sterile effluent. The method according to the present disclosure has the advantage that it allows simulating cumulative stress incurred by the filter during use with consideration to time and pressure, as closely as is feasible. A further advantage of the method according to the present disclosure is that it allows evaluating the impact of the stress incurred by the process filter during PUPSIT, while factoring in lab scale equipment/limitations and differing objectives, e.g., performing PUPSIT during manufacturing vs. filter validation.
The present invention relates to a method for validating the ability of a test filter unit to produce a sterile effluent. The method according to the present disclosure has the advantage that it allows simulating cumulative stress incurred by the filter during use with consideration to time and pressure, as closely as is feasible. A further advantage of the method according to the present disclosure is that it allows evaluating the impact of the stress incurred by the process filter during PUPSIT, while factoring in lab scale equipment/limitations and differing objectives, e.g., performing PUPSIT during manufacturing vs. filter validation.
A method of determining a flow velocity of a liquid medium comprises the following steps: a) measuring at least one parameter of the medium that is correlated with the density of the medium; b) predicting the density based on the measured parameter; c) measuring a flow velocity of the medium using an ultrasonic flowmeter (10); and d) calculating a corrected flow velocity based on the measured flow velocity and the predicted density. A device assembly for determining a flow velocity of a liquid medium comprises an ultrasonic flowmeter (10) for measuring a flow velocity of the medium, and at least one sensor (24) for measuring a parameter of the medium that is correlated with the density of the medium. The device assembly further comprises a processing unit (26) for predicting the density based on the measured parameter, and for calculating a corrected flow velocity based on the measured flow velocity and the predicted density. The device assembly is configured to perform the method defined above.
G01F 15/02 - Compensating or correcting for variations in pressure, density, or temperature
G01N 9/24 - Investigating density or specific gravity of materialsAnalysing materials by determining density or specific gravity by observing the transmission of wave or particle radiation through the material
G01F 1/667 - Arrangements of transducers for ultrasonic flowmetersCircuits for operating ultrasonic flowmeters
12.
TUBE REACTOR MODULE, USE OF TUBE REACTOR MODULE, AND INCUBATION DEVICE
The application relates to a tube reactor module for controlling a reaction time of a process fluid in dynamic operation, in particular during viral inactivation in the process fluid, comprising: an inlet for receiving the process fluid; an outlet for discharging the process fluid; a tubular flow path comprising a serpentine pattern for guiding the process fluid from the inlet to the outlet, the tubular flow path comprising a sequence of fluidly connected alternatingly bent curve sections, wherein each curve section is shaped such that a flow direction of the process fluid changes by at least approximately 90°, in particular by between approximately 135° and 225°, and wherein the tubular flow path comprises a first cross-section perpendicular to the flow direction of the process fluid at respective apexes of the curve sections and a second cross-section perpendicular to the flow direction of the process fluid at respective end portions of the curve sections, wherein the first cross-section is different from the second cross-section.
The invention relates to a method of separating empty viral capsids and full viral capsids, the method comprising: providing a viral capsid preparation comprising the empty viral capsids and the full viral capsids, wherein the viral capsid preparation comprises a first salt concentration; contacting the viral capsid preparation with a stationary phase surface allowing binding of the full viral capsids to the stationary phase surface, wherein the empty viral capsids at least partially do not bind to the stationary phase surface; and conducting a one-step and/or linear elution in which the full capsids are eluted by contacting the stationary phase obtained in step (ii) with an elution solution comprising a second salt concentration, wherein the first salt concentration is lower than the second salt concentration.
B01D 15/12 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
G01N 30/96 - Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography using ion-exchange
14.
BIOREACTOR, BIOREACTOR VESSEL AND CLOSURE COMPONENT FOR A BIOREACTOR VESSEL
Bioreactor, a Bioreactor Vessel and a Closure Component for a Bioreactor Vessel A closure component is provided for closing an upper opening of a rigid-walled bioreactor vessel, in use the vessel containing a biological medium and the upper opening providing access to the interior of the vessel. The component has: a lid having a mounting for fixing to a rim of the upper opening such that the lid closes the upper opening; a shaft which extends downwards from the lid; and one or more impellers mounted to the shaft. The mounting forms a bearing with the rim of the opening when fixed thereto. The lid, the shaft and the one or more impellers are integrally formed such that the component is a one-piece assembly in which the lid, the shaft and the one or more impellers are rotatable together as a single unit to stir the contents of the vessel.
Bioreactor and a Bioreactor Vessel A rigid-walled bioreactor vessel is provided for containing a biological medium. The vessel includes one or more heat exchange channels for exchanging heat with contents of the vessel. The or each channel is integrated into the wall of the vessel such that the material of the wall also forms the one or more 5 channels. The or each channel has a respective inlet configured to receive a flow of a heat exchange fluid into the channel, and a respective outlet configured to discharge the flow of the heat exchange fluid from the channel
The present invention relates to a filter module comprising a membrane (3), an edge structure (2), and an anchoring element (1), wherein the edge structure (2) is arranged over a surface of the membrane (3) in an edge region thereof and is embedded in the anchoring element (1), a difference between melting temperatures of the membrane (3) and the anchoring element (1) is from –25 K to 60 K, and a difference between melting temperatures of the edge structure (2) and the membrane (3) is 15 K or more. Moreover, the present invention relates to a method for producing the filter module as well as the use of the filter module for filtering a fluid medium.
The invention relates to a centrifuge for continuous flow centrifugation, wherein the centrifuge (1) comprises a drum (3), a rotor (4) and a motor (5) for driving the drum (3) and the rotor (4), wherein the centrifuge (1) comprises a drive bearing arrangement (7) with at least two drive roller bearings (8) with an inner race (9), an outer race (10) and a lubricant, wherein one of the drive roller bearings (8) comprises a sealing (11), wherein the drive roller bearings (8) rotate around the common rotation axis (A), wherein the drive bearing arrangement (7) comprises a bearing housing (12) with an outer wall (13). It is proposed that the outer wall (13) comprises a ridge (14) connected to the outer wall (13) by a connection providing a sealing (11) function and extending from the outer wall (13) towards the inner races (9) along the sealing (11).
The invention relates to a centrifuge for continuous flow centrifugation with drum (3), a rotor (4) and a motor (5), wherein the drum (3), driven by the motor (5), rotates around a common rotation axis (A) with a rotational frequency during use of the centrifuge (1), wherein the rotor (4) is coupled to the drum (3), wherein the centrifuge (1) comprises a drive bearing arrangement (7) with at least two drive ball bearings (8), wherein the drive ball bearings (8) each comprise an inner race (9), an outer race (10) and a bearing axis (B), wherein the drive ball bearings (8) rotate around the common rotation axis (A). It is proposed that the drive ball bearings (8) are angular drive ball bearings (8).
The invention relates to a pinch valve (2), including a pinching member (10), a base member (20) with a support section (22) facing the pinching member (10) and configured for receiving a tube (T), wherein the pinching member (10) is movable relative to the base member (20) along a pinching direction (4) for pinching the tube (T), and the support section (22) and/or the pinching member (10) comprises a recess (26) extending at least along the pinching direction (4) for receiving the tube (T) sectionally.
F16K 7/06 - Diaphragm cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage with tubular diaphragm constrictable by external radial force by means of a screw-spindle, cam, or other mechanical means
F16K 27/02 - Construction of housingsUse of materials therefor of lift valves
A61M 39/28 - Clamping means for squeezing flexible tubes, e.g. roller clamps
The invention relates to a centrifuge for continuous flow centrifugation with a drum (3), a rotor (4) and a motor (5) for driving the drum (3) and the rotor (4), wherein the drum (3), driven by the motor (5), rotates around a common rotation axis (A) with a rotational frequency during use of the centrifuge (1), wherein the rotor (4) is coupled to the drum (3), wherein the rotor (4) rotates around the common rotation axis (A) with the double of the rotational frequency, wherein the centrifuge (1) comprises at least one main bearing (7) between the rotor (4) and the drum (3) via which the rotor (4) is mounted onto the drum (3). It is proposed that the rotor (4) comprises at least one cooling fin (10) which moves air in a direction radially outwards from the common rotation axis (A) when the rotor (4) rotates.
The present invention relates to a filtration system for sterile filtration of particles having a hydrodynamic diameter of at most 400 nm as well as a method for sterile filtration of particles having a hydrodynamic diameter of at most 400 nm, both of which achieve a high yield of target molecules and sterility.
The present invention relates to a method of purifying biomolecules having a hydrodynamic diameter of at least 20 nm by using an integral porous polysaccharide membrane having chromatographically active centers. Moreover, the present invention relates to said integral porous polysaccharide membrane which has chromatographically active centers capable of binding a biomolecule having a hydrodynamic diameter of at least 20 nm, as well as a use of said membrane for purifying at least one type of biomolecules having a hydrodynamic diameter of at least 20 nm.
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 67/00 - Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
B01D 71/82 - Macromolecular material not specifically provided for in a single one of groups characterised by the presence of specified groups, e.g. introduced by chemical after-treatment
A valve device (10), especially for use with a small volume filtration device or for use in a fluid line in a pharmaceutical or biotechnology application, comprises a housing component (12) including a fluid chamber (22) and a fluid transfer opening (14) for establishing fluid communication with a first external fluid component. The valve device (10) further comprises a valve body (32) received in the housing component (12). The valve body (32) includes a hollow section (34), a first end cooperating with the fluid transfer opening (14) inside the housing component (12), a second end for connecting the valve device (10) to a second external fluid component, at least one first valve body opening (38) connecting the hollow section (34) with the fluid chamber (22) of the housing component (12), a second valve body opening (42) for fluid transfer from or to the second external fluid component, and a first thread structure formed at an outer wall of the valve body (32). The valve body (32) is translationally movable along an axis in the housing component (12) between an open position and a closed position. In the closed position of the valve body (32) the second end closes the fluid transfer opening (14) of the housing component (12). In the open position of the valve body (32) the second end is removed from the fluid transfer opening (14) of the housing component (12) so that a fluid connection is established between the fluid transfer opening (14) and the fluid chamber (22). The valve device (10) further comprises an actuator ring element (56) for actuating the valve device (10). The actuator ring element (56) is rotatably mounted on the housing component (12) and includes an accessible structure that can be engaged manually or by a tool to rotate the actuator ring element (56), and a second thread structure formed at an inner wall of the actuator ring element (56). The second thread structure engages the first thread structure of the valve body (32), so that a rotation of the actuator ring element (56) relative to the housing component (12) and the valve body (32) causes the valve body (32) to translationally move in the housing component (12). The valve device (10) further comprises means for sealing the fluid chamber (22) from the outside of the valve device (10).
F16K 3/24 - Gate valves or sliding valves, i.e. cut-off apparatus with closing members having a sliding movement along the seat for opening and closing with sealing faces shaped as surfaces of solids of revolution with cylindrical valve members
F16K 3/26 - Gate valves or sliding valves, i.e. cut-off apparatus with closing members having a sliding movement along the seat for opening and closing with sealing faces shaped as surfaces of solids of revolution with cylindrical valve members with fluid passages in the valve member
F16K 27/04 - Construction of housingsUse of materials therefor of sliding valves
24.
SINGLE-USE FLOW CELL, DETECTION DEVICE, ELECTRONICS DEVICE AND SYSTEM FOR THE USE IN A MULTIANGLE LIGHT SCATTERING MEASUREMENT
The present invention relates to a single-use flow cell (1) for the use in a multiangle light scattering measurement, comprising: a flow cell body (2), and a flow path (3) for passing a sample through the single-use flow cell (1), wherein the flow path (3) is provided at least in sections in the flow cell body (2). In order to provide a single-use flow cell (1) for the use in a multiangle light scattering measurement which can be easily produced it is provided that the single-use flow cell (1) is manufactured at least in sections by cold casting, injection molding, machining and/or additive manufacturing of an optical transparent material. The present invention also relates to a detection device (17), an electronics device (19) and a system (15) for the use in a multiangle light scattering measurement.
The invention relates to a single-use closed bioreactor for culturing, fermenting or processing a biomass with a rigid housing (3) with an interior space (4) with an inner height, an inner width and a volume smaller 100 L, wherein the rigid housing (3) comprises a lid (5) and a body, wherein the body comprises a wall (6), a top and a closed bottom (7) opposite to the top, wherein the top of the body is irreversibly connected to the lid (5) such that the top is closed by the lid (5), wherein the body comprises a bottom through port (11), wherein the bioreactor (1) comprises a stirrer shaft (10), wherein the stirrer shaft (10) is arranged on the lid (5) of the bioreactor (1) and extends from the lid (5) into the interior space (4) of the rigid housing (3), wherein the stirrer shaft (10) comprises a magnetic component, which is configured to interact with a magnetic drive located outside the body, wherein the bioreactor (1) comprises a first rigid support structure (13) extending from the lid (5) into the interior space (4) of the rigid housing (3), wherein the first rigid support structure (13) comprises a, in particular rigid, first conduit (14), wherein the lid (5) comprises a first inlet port (15) connected to the first conduit (14) via which a fluid can be exchanged with the interior space (4) of the rigid housing (3) through the first conduit (14).
The invention relates to a single-use closed bioreactor for culturing, fermenting or processing a biomass with a rigid housing (3) with an interior space (4) with an inner height, an inner width and a volume smaller 100 L, wherein the rigid housing (3) comprises a lid (5) with an upper surface (8) and a lower surface (9) and a body, wherein the body comprises a wall (6), a top and a closed bottom (7) opposite to the top, wherein the top of the body is irreversibly connected to the lid (5) such that the top is closed by the lid (5), wherein the lid (5) comprises a cooling structure (40) for cooling an exhaust gas of the bioreactor (1), wherein the cooling structure (40) comprises a cooling channel (41) with a channel ceiling (42) and a channel floor (43), wherein the cooling channel (41) has a channel inlet (44) at the lower surface (9) of the lid (5) within the interior space (4) of the housing and a channel outlet (45) at the upper surface (8) of the lid (5) outside the housing, wherein said cooling channel (41) has a horizontal section (46) which is at least partially oriented horizontally within the lid (5).
The invention relates to a Method of operating a process arrangement (1), in particular bioprocess arrangement, wherein the method comprises a separation of two phases of an aqueous-two-phase system (2). It is proposed that the process arrangement (1) comprises a fluidized bed centrifuge (3), that the fluidized bed centrifuge (3) is used for the separation of the two phases of the aqueous-two-phase system (2), that the aqueous-two-phase system (2) is loaded into a rotating chamber (4) of the fluidized bed centrifuge (3) as a fluid flow, that due to the rotation of the chamber (4) the aqueous-two-phase system (2) is centrifuged such that a first phase (7) of the two phases is separated 10 from a second phase (8) of the two phases, and, that due to the fluid flow during the rotation of the chamber (4), the first phase (7) remains in the chamber (4) while the second phase (8) leaves the chamber (4), such that the two phases are separated.
The invention relates to a filtration unit, in particular a syringe attachment filter or syringe filter holder, for filtering of a fluid, the filtration unit comprising: a first housing part comprising at least one first fluid chamber for a fluid to be filtered; a second housing part comprising at least one second fluid chamber for a filtered fluid; a filter element configured to fluidly connect the first chamber and the second chamber and to filter the fluid to be filtered; wherein the second housing part comprises: a support surface for supporting a fringe area of the filter element; and a rib element protruding from the support surface, at least a distal portion of the rib element consisting of or comprising a material substantially fusible by welding; wherein the first housing part comprises: an abutting surface for substantially abutting with the distal portion of the rib element, the abutting surface at least partly facing the support surface of the second housing part; and a barrier element protruding from the abutting surface towards the support surface and positioned relative to the rib element so as to laterally enclose an inner melt cavity therebetween, wherein the inner melt cavity upon welding is at least partially filled with solidified melt originating from fused material of the distal portion of the rib element, wherein the first housing part and the filter element and, optionally, the second housing part are to be coupled to one another via the solidified melt in the inner melt cavity.
B01D 27/00 - Cartridge filters of the throw-away type
B01D 29/01 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with flat filtering elements
B01D 29/11 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor with bag, cage, hose, tube, sleeve or like filtering elements
The present invention relates to a porous polymer membrane having the combination of a specific average pore diameter, a specific thickness, and a specific convective porosity. Moreover, the present invention relates to a method of manufacturing such porous polymer membrane.
B01D 67/00 - Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or propertiesManufacturing processes specially adapted therefor characterised by their properties
The present invention relates to a method for releasing a viral vector from a cell culture, wherein a cell of the cell culture is not required to be separated from the surrounding liquid prior to contacting the cell culture with the lysis reagent. The present invention further relates to a method for producing a viral vector inter alia comprising releasing the viral vector from a cell culture according to disclosed method for releasing a viral vector from a cell culture. The present invention further relates to a cell lysis reagent for releasing a viral vector from a cell culture. The present invention further relates to a kit for releasing a viral vector from a cell culture, wherein the kit comprises a container that contains the disclosed cell lysis reagent.
The present invention provides methods for releasing a viral vector from a cell culture. Specifically, the cell culture is contacted with a lysis reagent to generate a lysis composition and incubated, whereupon the lysis composition is contacted with an acidifying reagent to lower the pH. The method according to the present invention results in high viral vector release and reduction in co-released host cell related impurities. The present invention further provides a method for producing a viral vector. The present invention further provides a kit for releasing a viral vector from a cell culture. The present invention further provides a kit for producing a viral vector.
The invention relates to a method for controlling a bioprocess (1), wherein in a model control routine (5) a bioprocess control unit (4) controls at least one process parameter (6) of the bioprocess (1) according to a model-based control loop (7). It is proposed that during the model control routine (5) the bioprocess control unit (4) repeatedly performs a first evaluation (13) of the model-based control loop (7), that if a first decision criterion is fulfilled, the bioprocess control unit (4) switches from the model control routine (5) to a sample control routine (15), that in the sample control routine (15) the bioprocess control unit (4) controls the bioprocess (1) according to a sample-based control loop (23), that at least one sample input parameter (24) of the sample-based control loop (23) is derived from a measurement value.
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
G05B 13/04 - Adaptive control systems, i.e. systems automatically adjusting themselves to have a performance which is optimum according to some preassigned criterion electric involving the use of models or simulators
G05B 17/02 - Systems involving the use of models or simulators of said systems electric
33.
METHOD OF CONTROLLING A BIOPROCESS ARRANGEMENT TO PROVIDE MEASUREMENT DATA TO A BIOPROCESS CONTROL SYSTEM
The invention relates to a method of controlling a bioprocess arrangement (1) to provide measurement data to a bioprocess control system (3), wherein the bioprocess arrangement (1) comprises a biocontainer arrangement (2), a sampling arrangement (4), a routing arrangement (6) and an analysis arrangement (7). It is proposed that the bioprocess control system (3) sends a measurement request to the control layer (9), that the measurement request contains information about a requested measurement, that the measurement request is independent of routing and analysis behind the sampling arrangement (4), that the sampling arrangement (4) draws the sample and provides the sample to the routing arrangement (6), that the control layer (9) coordinates the provision of the sample to the analysis arrangement (7) via the routing arrangement (6), that the analysis arrangement (7) sends measurement data to the control layer (9), and, that the control layer (9) sends the measurement data to the bioprocess control system (3).
The invention relates to a test specimen (1) for rheological testing of plastic products comprising a plate body (10) from a plastic material, said plate body (10) having a first major surface (102), a second major surface opposite to the first major surface (102) and a side surface (106) connecting the first and the second major surface (104) and at least one spatial feature (12A, 12B, 14A, 14B) arranged in or on the plate body (10), each spatial feature (12A, 12B, 14A, 14B) indicative of a defect occurring in the plastic products or a geometric feature of the plastic products. The invention relates further to methods and respective systems using the test specimen, including methods and systems for testing for testing of a plastic product, for validating a rheological data set or a model of a process for manufacturing of plastic products, for determining at least one property of a plastic product to be manufactured and for manufacturing a plastic product.
The present invention concerns methods for processing and/or purification of a biological product involving multi-angle light scattering as analytical tool for process control. The methods of the invention apply multi-angle light scattering to detect the biological product, the presence of a bioburden or the functionality and/or integrity of a consumable employed in the method for processing and/or purification of the biological product. Further, the invention relates to systems for processing and/or purification of a biological product configured to perform the methods of the invention. Lastly, the invention concerns computer program products which can be used in the methods of the invention.
The present invention relates to a method of performing a gas/liquid-based integrity test, wherein air in a first membrane and a second membrane and present therebetween is replaced by a water-soluble gas before wetting the membranes. Further, the present invention relates to a method of producing an integrity-tested object having a first membrane, a second membrane and at least one boundary member.
A tubular flow device (10) for enabling controlled flow of a fluid at a measuring point comprises an inlet flow channel (14) defining a main inflow direction, and an outlet flow channel (18) defining a main outflow direction. The flow device (10) further comprises a branching portion (22) where the inlet flow channel (14) is divided into a primary flow channel (24) and a secondary measurement channel (26), and a joining portion (36) where the primary flow channel (24) and the secondary measurement channel (26) open into the outlet flow channel (18). The measuring point is located in the secondary measurement channel (26). The primary flow channel (24) is longer than the secondary measurement channel (26) and has a constriction (42) downstream of the branching portion (22). A fluid entering the inlet flow channel (14) is divided into a primary flow flowing into the primary flow channel (24) and a secondary measurement flow flowing into the secondary measurement channel (26). The primary flow and the secondary measurement flow reach the joining portion (36) essentially at the same time, due to the Venturi effect caused by the constriction (42) of the primary flow channel (24).
B33Y 80/00 - Products made by additive manufacturing
G01F 1/661 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters using light
G01F 5/00 - Measuring a proportion of the volume flow
G01F 15/00 - Details of, or accessories for, apparatus of groups insofar as such details or appliances are not adapted to particular types of such apparatus
A METHOD OF PRODUCING DIFFERENTIATED CELLS FROM PLURIPOTENT STEM CELLS, CELL POPULATIONS OBTAINED BY THE METHOD, CORRESPONDING PHARMACEUTICAL COMPOSITIONS AND A SYSTEM FOR PRODUCING DIFFERENTIATED CELLS FROM PLURIPOTENT STEM CELLS
The present invention inter alia relates to a method of producing differentiated cells from pluripotent stem cells, comprising providing at least one multicellular 3D aggregate derived from pluripotent stem cells cultured in a first suspension culture, inducing differentiation of the cells forming the at least one multicellular 3D aggregate, allowing a continuous release of differentiated cells from the multicellular 3D aggregate into the first suspension culture; and continuously separating the released differentiated cells from the first suspension culture. The present invention also relates to a cell obtained by the method and to a pharmaceutical composition comprising the cells. The invention further relates to a corresponding system for producing differentiated cells from pluripotent stem cells.
A bioprocess assembly (10) comprises a separation system (12) and a sampling system (14). The sampling system (14) is fluidically connected to the separation system (12) and comprises a sampling membrane (32) such that the separation system (12) and the sampling membrane (32) provide a separate sampling channel (30). The sampling channel (30) comprises at least one fluidic connection (36) to receive a buffer and at least one fluidic connection (51) to a sampling station (50). Further, the sampling channel (30) comprises a counter pressure generating unit (48) and at least one sensor (40), wherein the counter pressure generating unit (48) is configured to adjust the pressure within the sampling channel (30) based on data collected by the at least one sensor (40).
A device assembly (10) for performing a production scale tangential flow filtration of a feed, preferably in a batch feed and bleed process, comprises a first loop (12) including a first tubing (20), a feed tank (22) and actuators and sensors adapted to the first tubing (20), and a second loop (14) including second tubing (28) and a filter (28), preferably a hollow fiber filter. The first loop (12) and the second loop (14) further include a common tubing section. The first loop (12) connects to the second loop (14) at a first connection point (16) upstream, or alternatively downstream, of the filter (28), and the second loop (14) connects to the first loop (12) at a second connection point (18) downstream, or alternatively upstream, of the filter (28), such that the first loop (12) supplies the feed from the feed tank (22) to the second loop (14) at the first connection point (16), or alternatively at the second connection point (18), and the second loop (14) supplies retentate to the first loop (12) at the second connection point (18) from where a part of the retentate is returned to the feed tank (22), or alternatively at the first connection point (14). At least all wetted parts of the device assembly (10) are single-use parts and the inner diameter of the first tubing (20) is smaller than the inner diameter of the second tubing (32).
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12M 1/00 - Apparatus for enzymology or microbiology
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
41.
METHOD OF OPERATING A BIOPROCESS ARRANGEMENT TO PERFORM AT LEAST ONE REPETITION OF A BIOPROCESS
The invention relates to a method of operating a bioprocess arrangement (1) to perform at least one repetition of a bioprocess, wherein the bioprocess arrangement (1) comprises at least one replaceable electronic component (8), wherein a process control system (7) controls the bioprocess arrangement (1), using a digital model (10). It is proposed that the replaceable electronic components (8) are removed and replaced by new electronic components (9), that the process control system (7) automatically detects the removal of the replaceable electronic components (8), automatically detects the presence of the new electronic components (9) and retrieves digital representations (11) of the new electronic components (9) based on the communication with the new electronic components (9), that the process control system (7) derives from the digital representations (11) of the replaceable electronic components (8) and the new electronic components (9) a functional relationship between the replaceable electronic components (8) and the new electronic components (9), that the process control system (7) replaces the digital representations (11) of the replaceable electronic components (8) with the digital representations (11) of the new electronic components (9) based on the functional relationship thereby updating the digital model (10), and, that the process control system (7) controls the bioprocess arrangement (1) to perform the bioprocess based 20 on the updated digital model (10).
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control [DNC], flexible manufacturing systems [FMS], integrated manufacturing systems [IMS] or computer integrated manufacturing [CIM]
G05B 17/02 - Systems involving the use of models or simulators of said systems electric
A method of harvesting cell broth (12) from a mixing device (10) for mixing the cell broth (12) of a rocking motion bioreactor is shown. The mixing device (10) comprises a rocking motion platform (14), a mixing bag (18) and a processing unit (22). After a harvest process is started, the mixing bag (18) is tilted into a default harvest position and the cell broth (12) is harvested in the default harvest position of the mixing bag (18). If a pause condition is fulfilled, harvesting is paused and the mixing device starts rocking at a defined speed and a defined rocking angle for a predetermined time. After the predetermined time, harvesting in the default harvest position is resumed. Furthermore, a mixing device (10) for mixing cell broth (12) is disclosed.
A method of controlling a biopharmaceutical purification process, preferably a continuous process, making use of a separation arrangement. The separation arrangement preferably includes multiple chromatography columns or filtration devices. The method comprises the following steps: repeatedly acquiring an absorption spectrum inline or online at a fluid stream with a detector which is capable of recording spectra within a wavelength range between 190 nm and 2400 nm, preferably between 190 nm and 390 nm or 190 nm and 780 nm or 1100 nm and 2400 nm; real-time processing of the acquired spectrum; and real- time monitoring and controlling the process based on the processed spectrum. The step of processing includes at least one of the following measures: reducing noise; reducing spectral interference; correcting the acquired spectrum for scattering effects and/or other background effects.
The invention relates to a method for automating the foam regulation during a bioprocess for cultivating cells in a bioreactor, said method comprising the following steps: determining values of one or more process variables of the bioprocess which is/are relevant for the formation of foam in the bioreactor; transferring the determined values as input signals to a controller; generating, by the controller, output signals for at least one foam regulation device depending on the input signals; and controlling the at least one foam regulation device in a requirements-oriented manner by means of the output signals output by the controller.
A coupling device (1) for coupling to a flexible diaphragm (51) of a diaphragm device (50) and comprising a base structure (10) for attaching the diaphragm device (50) thereto; an actuator structure (20) mounted movable along an actuation direction (A) relative to the base structure (10) and having a diaphragm grasping element (22) pivotably mounted between a release position and a grasping position for coupling the actuator structure (20) to the flexible diaphragm (51) in the grasping position; and a fixation structure (30) mounted movable along a fixation direction (F) relative to the base structure (10) between an open position and a closed position and designed to fix in the closed position the diaphragm grasping element (22) against leaving the grasping position.
F16K 1/48 - Attaching valve members to valve-spindles
F16K 7/16 - Diaphragm cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage with flat, dished, or bowl-shaped diaphragm arranged to be deformed against a flat seat the diaphragm being mechanically actuated, e.g. by screw-spindle or cam
F16L 37/127 - Couplings of the quick-acting type in which the connection between abutting or axially-overlapping ends is maintained by locking members using hooks, pawls, or other movable or insertable locking members using hooks hinged about an axis
46.
METHOD FOR PERFORMING A TANGENTIAL FLOW FILTRATION ON A BIOMOLECULAR SOLUTION
The invention relates to a method for performing a tangential flow filtration on a biomolecular solution, in particular for performing a single pass tangential flow filtration on a biomolecular solution, as part of a production process for biomolecules, wherein a tangential flow filtration arrangement (1) is provided, wherein the tangential flow filtration arrangement (1) comprises a tangential flow filtration module (2), wherein the tangential flow filtration is performed inside the tangential flow filtration module (2), wherein the tangential flow filtration module (2) comprises a filter (3), a feed input fluid line (4) for the biomolecular solution as a feed medium, a retentate output fluid line (6) for a retentate, a filtrate output fluid line (7) for a filtrate, and preferably a buffer input fluid line (5) for a buffer, wherein the tangential flow filtration arrangement (1) comprises at least two actuators (8) influencing the tangential flow filtration, wherein the tangential flow filtration arrangement (1) comprises a control module (10), wherein the control module (10) controls the tangential flow filtration by providing control signals to the actuators (8) and measuring at least two measured variables (11) describing the tangential flow filtration, wherein the control module (10) uses a process control to control the tangential flow filtration. It is proposed that the process control is a model predictive control (13), that the control module (10) inputs the measured variables (11) as input variables (14) into the model and derives at least two manipulated variables (15) as control signals for the actuators (8).
The invention relates to a device for continuous virus inactivation during a protein production process, in particular an antibody production process, wherein the device comprises an axially extending hollow-body holder (1) for holding an elongated, elastically deformable hollow body (2), in particular a flexible tube, wherein the device comprises at least two axially extending rollers (3, 4), in particular three or four rollers (3, 4, 5, 6), each of which, when the device has been assembled as intended, squeezes the hollow body (2) and thereby divides the internal volume (7) of the hollow body (2) into volume portions (8) fluidically separated from one another, wherein the continuous virus inactivation is carried out in the volume portions (8) of the hollow body (2). It is proposed that the device comprises a support element (9) which, when the device has been assembled as intended, supports the lateral faces of each of the rollers (3, 4, 5, 6) in at least one point.
C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
A61L 2/00 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12M 1/00 - Apparatus for enzymology or microbiology
B01D 15/24 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the treatment of the fractions to be distributed
48.
METHOD OF OPERATING A BIOPROCESSING ARRANGEMENT COMPRISING A CLARIFICATION SET-UP TO REMOVE CELL DEBRIS FROM A CELL BROTH
The invention relates to a method of operating a bioprocessing arrangement (1) comprising a clarification set-up (2) to remove cell debris from a cell broth (10), wherein the clarification set-up (2) comprises a fluidized bed centrifuge (8) with at least one centrifuge chamber (11), wherein the cell broth (10) is separated into at least a waste fraction (12) and an output fraction (13), wherein the separation of the cell broth (10) into the waste fraction (12) and the output fraction (13) comprises a loading step (14) during which the centrifuge chamber (11) is loaded with cells of the cell broth (10) up to a capacity below or equal to a maximum cell loading capacity of the centrifuge chamber (11), an overloading step (15) during which the centrifuge chamber (11) is further loaded with cell broth (10), thereby flushing out cells from the centrifuge chamber (11), collecting cells flushed out during the overloading step (15) as the waste fraction (12), and collecting cells from the chamber as the output fraction (13).
The invention relates to a an aeration device for a bioprocessing installation (2), comprising a housing (4), a circumferential rigid body (5), wherein the housing (4) comprises at least a first aeration channel (7) and a second aeration channel (8), wherein the housing (4) further comprises at least a first gas inlet port (10) and a second gas inlet port (11), and wherein the housing (4) further comprises a plurality of first gas discharge openings (12) and second gas discharge openings (13). It is proposed that the first aeration channel (7) and the second aeration channel (8) are arranged so as to overlap one another in the axial direction at least in sections.
A filtration device (10), in particular a small-scale filtration device for production of biopharmaceuticals, comprises a housing including a top cover (12) having an unfiltrate inlet (18) and a bottom cover (14) having a filtrate outlet (22), and one or more filter supports (16) stacked between the top cover (12) and the bottom cover (14) along a vertical direction such that an upper side of each filter support (16) faces the top cover (12) and a lower side of each filter support (16) faces the bottom cover (14). Each filter support (16) is equipped with a flat upper filter (40) and a flat lower filter (42). Each filter (40, 42) has a filtrate side and an opposite unfiltrate side. The upper and lower filters (40, 42) are sealed to the upper and lower sides of the filter support (16), respectively, with the filtrate sides facing the filter support (16) and the unfiltrate sides facing away from the filter support (16). Unfiltrate flow paths lead from the unfiltrate inlet of the top cover (12) to the unfiltrate side of the upper filter (40) and to the unfiltrate side of the lower filter (42), wherein blocking means prevent unfiltrate from flowing directly from the unfiltrate inlet of the top cover (12) to the filtrate outlet (22) of the bottom cover (14). Filtrate flow paths lead from the filtrate sides of the upper and lower filters (40, 42) to the filtrate outlet (22) of the bottom cover (14) via at least one filtrate guiding channel (48a, 48b) formed on the upper side of the filter support (16) and at least one filtrate guiding channel (48a, 48b) formed on the lower side of the filter support (16). The upper filter (40) and the lower filter (42) are identically shaped.
The present invention relates to a method for treating an ultrafiltration membrane, a method for producing an ultrafiltration membrane comprising the treatment method, as well as ultrafiltration membrane obtained by the treatment method or the production method.
The invention relates to a portable container holder for use in a bioprocess for holding and transporting a disposable container (3) which is filled with a fluid (2) and which has received a magnetically driven mixing element (4) for mixing the fluid (2), wherein the portable container holder (1) has a container receiving area (7) for receiving the disposable container (3), said receiving area having a drive location (8) where the mixing element (4) can be arranged in the disposable container (3) received in the container receiving area (7) such that the mixing element (4) can be driven by a drive unit (9) at the drive location (8). According to the invention, the portable container holder (1) has a transport securing unit (11) for securing and releasing the mixing element (4), which is arranged at the drive location (8), in its position, and the transport securing unit (11) has a magnet (10) which can be moved between a defined securing position (12), in which the mixing element (4) is secured in its position, and a defined release position (13), in which the mixing element (4) is released from its position.
The invention relates to a portable container holder for use in a bioprocess for holding and transporting a flexible disposable container (3) which is filled with a fluid (2). In particular, the fluid (2) is a fluid (2) which contains a purified pharmaceutical ingredient or a cultivation medium, and the portable container holder (1) has a container receiving area (6) for receiving the disposable container (3) and a cover (7) which can be installed on the container receiving area (6) in order to cover (7) the disposable container (3) received in the container receiving area (6), wherein the cover (7) has a fixing assembly (8) via which the disposable container (3) filled with the fluid (2) can be fixed in the container receiving area (6) in the installed state of the cover (7). According to the invention, the cover (7) has a spring assembly (9) which elastically supports the fixing assembly (8), and a spring force can be applied to the fixing assembly (8) in the direction of the spring via the spring assembly (9) in the installed state of the cover (7).
The invention relates to a bioprocess system for a bioprocess operation with a display arrangement (21) for displaying system information about the bioprocess system (1), wherein the bioprocess system (1) comprises system components (6) comprising at least one monitored system component (22), wherein the system components (6) can be assembled into an assembled state in which the bioprocess system (1) is operational for the bioprocess operation and can be disassembled into a disassembled state in which the bioprocess system (1) is not operational for the bioprocess operation, wherein the bioprocess system (1) comprises a control arrangement (24) and the display arrangement (21) comprises at least one display component (25), wherein in an assembled state of the bioprocess system (1) during a bioprocess operation the control arrangement (24) displays process information via the display arrangement (21) and/or wherein during assembly of the bioprocess system (1) the control arrangement (24) displays assembly information via the display arrangement (21), wherein the process information and/or the assembly information concern at least the monitored system component (22) and wherein the display arrangement (21) comprises at least one display component (25). It is proposed that the display component (25) comprises a light emitting element (27) arranged separate from the monitored system component (22) and arranged next to or on the monitored system component (22) and that the control arrangement (24) is configured to display via the light emitting element (27) the process information and/or the assembly information relating to the monitored system component (22).
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
G05B 19/409 - Numerical control [NC], i.e. automatically operating machines, in particular machine tools, e.g. in a manufacturing environment, so as to execute positioning, movement or co-ordinated operations by means of programme data in numerical form characterised by using manual data input [MDI] or by using control panel, e.g. controlling functions with the panelNumerical control [NC], i.e. automatically operating machines, in particular machine tools, e.g. in a manufacturing environment, so as to execute positioning, movement or co-ordinated operations by means of programme data in numerical form characterised by control panel details or by setting parameters
G06F 9/448 - Execution paradigms, e.g. implementations of programming paradigms
G05B 19/40 - Open loop systems, e.g. using stepping motor
G05B 19/042 - Programme control other than numerical control, i.e. in sequence controllers or logic controllers using digital processors
The invention relates to a method for inactivating viruses in a fluid, in which method: a starting fluid (AF) containing active viruses is mixed with a virus-inactivating reagent (R1) in a first mixing assembly (2) to form a reactive fluid (F); the active viruses are inactivated via incubation of the reactive fluid (F); and the inactivation of the viruses in the reactive fluid (F) is stopped by mixing the reactive fluid (F) with a further reagent (R2) or by removing the virus-inactivating reagent (R1) from the reactive fluid (F), as a result of which a resulting fluid (RF) is produced. According to the invention, the active viruses are inactivated via incubation of the reactive fluid (F) in a container assembly (3) which comprises a plurality of separate containers (4) and differs from the first mixing assembly (2), wherein the reactive fluid (F) is conducted from the first mixing assembly (2) to the container assembly (3) prior to incubation.
The invention relates to a method for generating and purifying viral vectors (V), wherein the viral vectors (V) are generated by cells in a fluid (F) and wherein the fluid (F) comprising the viral vectors (V) is guided through a tangential flow filtration arrangement (2) for purification, whereby the viral vectors (V) are purified in the fluid (F). It is proposed that the cells and cell debris from the cells, which are contained in the fluid (F) comprising the viral vectors (V) after generating the viral vectors (V), are at least partially separated from the viral vectors (V) by a fluidized bed centrifuge (5) before purification by the tangential flow filtration arrangement (2).
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
The present invention relates to methods for the purification of viruses, virus-like particles, extracellular vesicles, proteins having a diameter of 5 nm or more, protein complexes having a diameter of 5 nm or more, nucleic acids having a diameter of 5 nm or more, protein-nucleic acid complexes having a diameter of 5 nm or more, and/or molecules having a diameter of 5 nm or more, by filtration-supported polyalkylene glycol precipitation, and to filtration modules that can be used in said methods.
The invention relates to a method for operating a continuous downstream process, in particular a continuous virus activation or inline dilution process, using a bio-process arrangement (1), wherein the bio-process arrangement (1) has a compensating container (2) with a first fluid inlet (3), configured for introduction of a concentrate stream, in particular a product or buffer concentrate stream, into the compensating container (2), with at least one second fluid inlet (4), configured for introduction of a diluent stream, in particular a product or buffer diluent stream, into the compensating container (2), with a fluid outlet (5), configured to discharge a liquid stream from the compensating container (2), wherein the bio-process arrangement (1) has a conveying arrangement (6) for fluid conveyance, which is allocated to the first fluid inlet (3) and to the second fluid inlet (4) for conveying in each case at least one liquid stream into the compensating container (2), and is allocated to the fluid outlet (5) for conveying a liquid stream out of the compensating container (2), and wherein the bio-process arrangement (1) has an electronic process control (7). It is proposed that the electronic process control (7) adapts, by controlling the conveying arrangement (6) in an open-loop and/or closed-loop manner, a fill level in the compensating container (2) such that a predefined minimum fill level in the compensating container (2) is always reached.
B01F 23/40 - Mixing liquids with liquidsEmulsifying
B01F 35/83 - Forming a predetermined ratio of the substances to be mixed by controlling the ratio of two or more flows, e.g. using flow sensing or flow controlling devices
The invention relates to a method for performing an integrity test on a testing consumable (1) of a bioprocess installation using a test arrangement (2), wherein during a test routine (26), which is being performed by a test control unit (3) of the test arrangement (2), a predetermined test procedure is being applied to the testing consumable (1) via the test arrangement (2) and an integrity state is being derived from process data that have been collected during the test routine (26). It is proposed that during the test routine (26), early process data (27), that are being generated by a testing sensor arrangement (4) of the test arrangement (2) in an early stage of the test procedure, are being used to determine the integrity state of the testing consumable (1) by correlating in a correlating step (28) the early process data (27) to a system model (29) of a reference module (30), which reference module (30) emulates a, in particular integral, testing consumable (1) only in view of predetermined process data.
C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
B01D 65/10 - Testing of membranes or membrane apparatusDetecting or repairing leaks
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
G01M 3/22 - Investigating fluid tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for pipes, cables, or tubesInvestigating fluid tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for pipe joints or sealsInvestigating fluid tightness of structures by using fluid or vacuum by detecting the presence of fluid at the leakage point using special tracer materials, e.g. dye, fluorescent material, radioactive material for valves
G01N 15/08 - Investigating permeability, pore volume, or surface area of porous materials
61.
HOLDING DEVICE FOR A CONTAINER, HAVING A MAGNETIC DRIVE FOR A SEPARATE AGITATOR SHAFT
The invention relates to a holding device (26) for a container, in particular a bioreactor, comprising a magnetic drive (30) for a separate agitator shaft (28) and a lever device (10) for releasing the agitator shaft (28) from the magnetic drive (30). The magnetic drive (30) has a first coupling side (32) and the agitator shaft (28) has a second coupling side (34) of a magnetic coupling, said second coupling side being connectable to the first coupling side (32). The lever device (10) has at least one pressure portion (22; 64) and is pivotable between a closing position and a release position. As the lever device (10) is pivoted into the release position, the pressure portion (22; 64) is moved downwards in order to act directly or indirectly on the agitator shaft (28).
B01F 33/453 - Magnetic mixersMixers with magnetically driven stirrers using supported or suspended stirring elements
B01F 27/213 - Mixers with rotary stirring devices in fixed receptaclesKneaders characterised by their rotating shafts characterised by the connection with the drive
62.
METHOD FOR OPERATING A BIOPROCESS INSTALLATION FOR PRODUCTION OF A BIOPRODUCT
The invention relates to a method for operating a bioprocess installation (1) for production of a bioproduct, wherein the bioprocess installation (1) comprises a source receptacle (2) for cell cultivation, a harvest receptacle (3) for bioproduction and a clarification setup (4) with a centrifuge (12), wherein the source receptacle (2) is operated in a cyclical production mode comprising the steps of: a) starting the cyclical production mode in the source receptacle (2) b) cultivating the cells in the source receptacle (2), thereby obtaining a cell broth (7) comprising cultivated cells, c) discharging a discharge fraction (16) of the cell broth (7) from the source receptacle (2), d) combining a restart fraction (17) of the cell broth (7) with fresh cultivation medium (8) and repeating step b), e) repeating steps c) and d) at least once and/or f) discharging the cell broth (7) obtained from step d) from the source receptacle (2) stopping the cyclical production mode, obtaining a discharge fraction (16), wherein the method further comprises the steps of: i) centrifuging the discharge fraction (16) via the centrifuge (12), thereby separating the discharge fraction (16) into at least a centrifuged discharge fraction (19) and supernatant (14) and preferably bioproduct, ii) operating the harvest receptacle (3) in a production mode, wherein steps i) and ii) are executed at least twice.
The invention relates to a method for a dynamic in-line mixing process of a pressurized medium (1), which contains a liquid and at least one additional liquid or solid constituent, in a bioprocess assembly (3). The liquid is combined with the at least one additional liquid or solid constituent in a specified volume ratio at an opening point (4) in order to form a resulting liquid flow (5), wherein the bioprocess assembly (3) has a pump assembly (8) with a first pump (9), the first pump (9) is arranged in the line (7) of the line assembly (6), the first pump (9) is designed as a rotary pump (10), in particular a centrifugal pump, which is designed for a dynamic in-line mixing process of the medium (1), the first pump (9) has a liquid inlet (9a) which forms the suction side of the pump when operated as intended and a liquid outlet (9b) which forms the pressure side of the pump when operated as intended, and the medium (1) is conducted through the rotary pump (10) for a dynamic in-line mixing process. According to the invention, the medium flows through the rotary pump (10) in the opposite flow direction, in comparison to the intended operation, for the dynamic in-line mixing process.
Disclosed is inter alia a method for validating a filter unit, wherein the method comprises: - guiding a fluid flow of a fluid, after the fluid flow passed through the filter unit, to a measurement area that is connected to the filter unit, wherein within the measurement area the fluid is exposed to at least one alternating electric field between at least two electrodes; - obtaining at least one electric signal between the at least two electrodes, wherein the at least one electric signal is at least affected by whether one or more cells of a plurality of cells in the fluid pass through the measurement area; and - determining, at least partially based on the obtained at least one electric signal, at least one validity information indicating a validity of the filter unit.
A bioreactor system (10) for carrying out a biological process comprises a container (12) for receiving a liquid biological medium and a gas supply facility for feeding various gases from gas sources (38, 40, 42, 44) into the container (12) in a controlled manner. The gas supply facility has a plurality of gas outlet lines (28, 30, 32) which open into one or more gas supply devices (20) and/or into an overlay gas outlet in the interior of the container (12). Each gas outlet line (28, 30, 32) is connected to multiple gas sources (38, 40, 42, 44) by a respective gas supply line (46, 52, 56, 58) or by a respective branch (48, 50, 54, 60) of a gas supply line (46, 52, 56, 58). A mass flow regulator (62), which is connected to a control unit, is arranged in each gas supply line (46, 52, 56, 58) and in each branch (48, 50, 54, 60). Such a bioreactor system for carrying out a biological process preferably comprises a controller, which comprises a master regulator for a controlled variable, at least one sensor associated with the master regulator and one or more follower regulators with actuators (14, 62), the manipulated variables of which influence the controlled variable in a targeted manner. The controller is designed such that a setpoint value for the controlled variable can be prespecified to the master regulator, the at least one sensor is used for repeated determination of an actual value of the controlled variable, and the master regulator provides to the follower regulators an output signal dependent upon the deviation of the actual value of the controlled variable from the setpoint value of the controlled variable. Control profiles, which are dependent upon the output signal of the master regulator, are assigned to the follower regulators. According to a first alternative, the control profiles contain setpoint values for the actuators (14, 62) of the follower regulators, and the controller is designed such that the setpoint values for the actuators (14, 62) can be input in the physical unit of their manipulated values. According to a second alternative, the control profiles contain setpoint values for a parameter that relates directly to the biological process and can be influenced in a targeted manner by the actuators (14, 62), and the controller is designed such that it automatically assigns setpoint values for the actuators of the follower regulators to the parameter setpoint values.
The invention relates to a flow-through centrifuge (1), which can be used for example for biotechnological applications, in particular in the form of a blood centrifuge (2). A drive and/or transmission assembly (19) of the through-flow centrifuge (1) has a planetary transmission (62). At least one planetary belt pulley (34; 36) is rotatably mounted on a rotating planet carrier (18) in the planetary transmission (62), and the torque of the planetary belt pulley (34; 36) is transmitted via a belt (33; 37), wherein the planet carrier (18) and the belt pulley (34; 36) are driven at different rotational speeds. According to the invention, the planet carrier (18) is held via a belt-tensioning unit (17) which rotates together with the planet carrier (18), and the distance (42) between the planet carrier (18) and a rotor axis (4) can be modified via the belt-tensioning unit (17) in order to set the tension of the belt (33; 37).
The invention is directed to a method for producing a roll (1) or sheet of membrane units (2) for a membrane product (3) such as a lateral flow test from a roll (6) or sheet of membrane material (7), by means of a primary production arrangement (9), wherein the roll (6) or sheet of membrane material (7) is processed into a roll (1) or sheet of membrane units (2) in a primary processing routine, wherein in the primary processing routine, for generating the membrane units (2), a fluidic structure (11), in particular a hydrophobic structure, for defining fluid flow through the membrane material (7) is introduced into the membrane material (7) by means of a processing tool (12), wherein an evaluation routine is performed by means of an evaluation arrangement (15) comprising a sensor arrangement (16) and an evaluation control (17). It is proposed that in the evaluation routine, evaluation images (18) of the fluidic structures (11) of the membrane units (2) are generated by means of the sensor arrangement (16) and evaluation data (19) are generated by means of the evaluation control (17) and that the evaluation data (19) represent the deviation in predefined geometrical properties of the fluidic structure (11) in the respective evaluation image (18) with respect to the fluidic structure (11) in a reference image (21).
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
G01N 33/531 - Production of immunochemical test materials
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control [DNC], flexible manufacturing systems [FMS], integrated manufacturing systems [IMS] or computer integrated manufacturing [CIM]
68.
LIPID NANOPARTICLE PRODUCTION SYSTEM AND METHOD OF MONITORING AND CONTROLLING THE SAME
The present invention relates to automated nanoparticle synthesis systems and computer-implemented methods of monitoring and controlling a process of manufacturing lipid nanoparticles (LNPs) containing nucleic acid cargo. The present invention furthermore relates to a computer program product comprising computer-readable instructions, which, when loaded and executed on a computer system, causes the computer system to perform operations according to said methods.
The invention relates to a centrifuge (19), in particular a continuous-flow centrifuge, a biotechnical centrifuge or a blood centrifuge. The centrifuge (19) is provided with a coolant circuit (1). According to the invention, the outlet side of a controllable compressor (4) is connected to an inlet side of an evaporator (2) via a bypass line (5) with a valve (20) arranged therein. In a normal operating mode, when the valve (20) is closed, the cooling of a centrifuge bowl (3) occurs exclusively via the control of the compressor (4) and an expansion unit (6). However, if the target temperature in the centrifuge bowl (3) falls below a tolerance range, the valve (20) is opened in order to bring about a heating process and thereby a returning of the temperature in the centrifuge bowl (3) to within the tolerance range.
The present invention relates to tangential flow filtration/chromatography systems, the use thereof, and methods of separation, particularly simultaneously separating one or more target molecules from cells, cell debris and further contaminants contained in e.g. fermentation broth or any other particulate and impurity containing, non-clarified liquid.
B01D 15/22 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
The present invention relates to a filter module comprising an ester-based membrane and at least one boundary member, wherein the peripheral region of the membrane is connected to the at least one boundary member, and wherein the surface of the membrane is saponified in the regions other than the peripheral region connected to the at least one boundary member. Further, the present invention relates to a method of producing such filter module and to the use of such filter module.
The application relates to a sensor holding device for holding a sensor device, in particular a clamp-on flow measurement sensor, the sensor holding device comprising: a holding body configured for holding the sensor device, wherein the holding body comprises: a sensor holding device-side engaging means for engaging with a sensor device-side engaging means of the sensor device when the sensor device is held by the holding body; and a securing means connected to the holding body for securing the sensor device at the holding body, the securing means being moveable relative to the holding body to a first position and to a second position, wherein the securing means moved into the first position allows placing the sensor device onto the holding body and removing the sensor device from the holding body, and wherein the securing means moved into the second position and the sensor holding device-side engaging means engaging the sensor device-side engaging means restrict relative movement of the sensor device along three directions with respect to the holding body such that the sensor device is secured at the holding body.
The present invention relates to a filter system, which can be used as a clarification filter/depth filter for cell culture clarification before chromatography and/or ultrafiltration for protein purification, as well as to a method of separating cells and other contaminants from a fluid containing one or more target components by employing the filter system of the present invention.
B01D 15/12 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
A bioreactor for cell cultivation comprises a reusable reactor vessel (16), preferably made of stainless steel, for receiving a fluid, and an optical spectroscopy interface (14) including an adapter (10) and a single-use optical spectroscopy insert (12). The reusable reactor vessel (16) has a wall (18) and a port formed in the wall (18). The adapter (10) is configured to be fixed to the port in a predefined position at the port. The single-use optical spectroscopy insert (12) is configured to be accommodated and fixed in the adapter (10), or the insert (12) is an integral part of the adapter (10).
C12M 1/00 - Apparatus for enzymology or microbiology
75.
SYSTEM FOR DETECTING A MEASUREMENT VARIABLE OF A FLUID BEING CONDUCTED IN A FLUID-CONDUCTING LINE, FLOW-THROUGH DEVICE FOR ARRANGING ON A FLUID-CONDUCTING LINE AND FOR ATTACHING A FLOWMETER, AND USE OF A FLOW-THROUGH DEVICE
The invention relates to a system for detecting a measurement variable of a fluid being conducted in a fluid-conducting line, said system having: - a flowmeter, in particular an ultrasonic flow meter, for detecting the measurement variable, - a flow-through device (10) for arranging on the fluid-conducting line and for attaching the flowmeter for detecting the measurement variable of the fluid being conducted by the line, said flowmeter having: - a first and second connection (12, 14), by means of which the flow-through device (10) can be connected to the fluid-conducting line, and - a measurement region (16) which is arranged between the first connection (12) and the second connection (14) and which can be coupled to the flowmeter for detecting the measurement variable, wherein the first connection (12), the measurement region (16), and the second connection (14) define a flow path (A) for the fluid through the flow-through device (10), and the measurement region (16) has at least two contact surfaces (20), which extend at least partly along the flow path (A), for contacting the flowmeter. The at least two contact surfaces (20) are designed to separate a coupling means under the effect of a pressing force, and the flowmeter is designed so as to exert at least the pressing force onto the at least two contact surfaces (20) by means of a coupling of the flowmeter to the measurement region (16). The invention additionally relates to a flow-through device and to a use thereof.
G01F 1/667 - Arrangements of transducers for ultrasonic flowmetersCircuits for operating ultrasonic flowmeters
G01F 1/66 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters
G01F 15/00 - Details of, or accessories for, apparatus of groups insofar as such details or appliances are not adapted to particular types of such apparatus
G01F 15/18 - Supports or connecting means for meters
76.
METHOD OF REFERENCING AN ANALYTE MEASUREMENT IN A PURIFICATION SYSTEM
In a method of referencing an analyte measurement in a purification system during a process step in a biopharmaceutical process, the following sub-steps are performed during the same process step: guiding a medium through a purification unit (10) where the analyte is either removed from or added to the medium; measuring at least one parameter related to the presence and/or quantity of the analyte with a first measurement system (16) at a first measurement location upstream of the purification unit (10); measuring the at least one parameter with a second measurement system (18) at a second measurement location downstream of the purification unit (10); and referencing the upstream measurement to the downstream measurement, or referencing the downstream measurement to the upstream measurement.
DEVICE FOR ARRANGING ON A FLUID-CONDUCTING LINE AND FOR ATTACHING A FLOWMETER, AND METHOD FOR DETECTING A MEASUREMENT VARIABLE OF THE FLUID BEING CONDUCTED BY A LINE
The invention relates to a device (10) for arranging on a fluid-conducting line and for attaching a flowmeter, in particular an ultrasonic flowmeter, for detecting a measurement variable of the fluid being conducted by the line, having: - a first and a second connection (12, 14), by means of which the device (10) can be connected to the fluid-conducting line, - a measurement region (16) which is arranged between the first connection (12) and the second connection (14) and which can be coupled to the flowmeter in order to detect the measurement variable, wherein the first connection (12), the measurement region (16), and the second connection (14) define a flow path (A) for the fluid through the device (10), and - a flow-influencing element (22) which is arranged in and/or on the flow path (A) and which is arranged in front of the measurement region (16) in a provided flow direction of the fluid along the flow path (A) and at a distance therefrom. The flow-influencing element (22) is integrally formed with the first connection (12) or the second connection (14), and the flow-influencing element (22) is designed such that the flow flowing into the device (10) via the first connection (12), said fluid flowing into the device (10) with a substantially laminar flow, has a substantially turbulent flow in the measurement region (16).
G01F 1/66 - Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters
G01F 1/667 - Arrangements of transducers for ultrasonic flowmetersCircuits for operating ultrasonic flowmeters
G01F 15/00 - Details of, or accessories for, apparatus of groups insofar as such details or appliances are not adapted to particular types of such apparatus
G01F 15/18 - Supports or connecting means for meters
F15D 1/02 - Influencing the flow of fluids in pipes or conduits
78.
MULTIPORT DEVICE FOR CONNECTING A LOOP TO ONE PORT OF A BIOREACTOR, AND PERFUSION OR CONCENTRATED FED-BATCH SETUP FOR PERFORMING AN UPSTREAM PROCESS OF CELL CULTURE
A multiport device (42) for connecting a loop (36), preferably a tangential flow filtration loop or a sensor loop, to one port (34) of a bioreactor (32), preferably a single-use bioreactor (32), is configured to be fixed to the port (34) of the bioreactor (32). The multiport device (42) includes a first flow path (44) configured for 5 withdrawing fluid from the bioreactor (32), and a second flow path (52) configured for supplying fluid to the bioreactor (32). The first flow path (44) has a first end (48) adapted to be in fluid connection with the bioreactor (32), and a second end (50) adapted to be connected to an inlet of the loop (36). The second flow path (52) has an outer end (64) adapted to be connected to an outlet of the loop (36), and a 10 mouth (62) adapted to be in fluid connection with the bioreactor (32). The mouth (62) of the second flow path (52) is distanced from the first end (48) of the first flow path (44) by at least 5 mm, preferably 10 mm.
A device assembly (10) for calibrating a single-use sensor (14) before, during or after a biopharmaceutical manufacturing process step comprises a single-use process equipment assembly for performing at least a part of the process step. The single-use process equipment assembly includes a flow line (12) through which a medium flows in a defined direction during the process step. The single- use process equipment assembly further includes an integrated single-use sensor (14) for measuring or detecting a physical or chemical property at a measurement location in the flow line (12). The device assembly (10) further comprises at least one calibration line (18) and at least one switching means (22) inserted into the flow line (12) upstream of the measurement location. The switching means (22) include a flow line inlet, a flow line outlet and a calibration line inlet connected to the calibration line (18). The switching means (22) are adapted to selectively switch between a first (main) flow path, in which the flow line inlet (26) and the flow line outlet (28) are opened while the calibration line inlet (30) is closed, and a second (calibration) flow path, in which the flow line inlet (26) is closed while the calibration line inlet (30) and the flow line outlet (28) are opened. The device assembly (10) comprises a dedicated reference means provided in the calibration line (18). The dedicated reference means includes a reference sensor (48) or a reference source or a reference standard solution (40) related to the physical or chemical property to be measured or detected by the single-use sensor (14). The calibration line (20) may also be provided downstream of the single-use sensor (14).
A modular system for providing a bioprocess device assembly comprises a rigid skid (10) and a plurality of grid-modules (12). The skid (10) includes a plurality of identical plug-in structures (14) being arranged in a regular two-dimensional grid. The grid arrangement of the plug-in structures (14) defines two-dimensional plug-in fields (20) of an identical standard shape and size. At least some of the grid- modules (12) have a matching counterpart plug-in structure (22) adapted to fix the respective grid-module (12) to any of the plug-in structures (14) of the skid (10). At least some of the grid-modules (12), in an installed state when fixed to a plug-in structure (14) of the skid (10) and/or to a neighboring grid-module (12), have a two- dimensional extension in the plane of the grid that is not greater than the standard size of the plug-in fields (20). At least some of the grid-modules (12) include at least one connection port (30) adapted to receive a rigid universal flow connector (26; 34) of standard shape and size in a standard position and orientation. The universal flow connector (26; 34) establishes a flow connection between two neighboring grid-modules (12). The connection port (30) of each grid-module (12) defines the standard position and orientation of the universal flow connector (26; 34) such that, in its installed state, the grid-module (12) can be connected via the universal flow connector (26; 34) either directly to the connection port (30) or to another universal flow connector (34) received in the connection port (30) of an opposing grid-module (12) fixed to the grid-module (12) and/or to a neighboring plug-in structure (14). At least some of the grid-modules (12) have at least one integrated fluid line (32) through, or into, which a medium to be processed or analyzed can flow. The integrated fluid line (32) is in flow communication with the connection port (30) of the grid-module (12). The plurality of grid-modules (12) includes at least one flow control grid-module having means for actively changing flow properties of the medium, and/or at least one interaction grid-module having means for sensing, detecting or measuring a property of the medium.
Some aspects of the disclosure are related to systems and methods for controlled oxygen release from biomaterials in vessels and unit operations or components of cell culture, cell containment, and/or bioreactor. Vessels, unit operations, devices, and/or components of the invention may be used to perform all or part of a biological and/or chemical process involving biologicals (e.g., a plurality of cells) in the presence of oxygen-releasing agents. In some embodiments, a system comprises a vessel comprises an oxygen-releasing agent configured to generate in- situ and release oxygen in a sustained manner. The presence of an oxygen-releasing agent may advantageously allow for high cell density fermentation and cell cultivation in a vessel and provide an alternative for supplemental gassing means (e.g., sparger, etc.). Some embodiments of the disclosure are directed to employing the oxygen-releasing agents in microfluidic or millifluidic systems.
The present invention relates to a separation system for separating and purifying a target component, a method for separating and purifying a target component, and the use of a single-pass crossflow diafiltration unit for integrally connecting a first and a second chromatography device.
B01D 15/18 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/24 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the treatment of the fractions to be distributed
Containers including internal mixers and actuators assemblies and related methods are generally described. In some embodiments, a container may include a mixer and an actuator, at least one of which may be located inside of the container. The actuator may actuate the mixer to induce flow within the container and mix the contents of the container with a low volumetric footprint and high mixing efficiency. In some embodiments, the actuator may be configured to deform the mixer, which may include one or more features which may be deformed out of plane in a Kirigami or Origami fashion. The actuator and mixer may be arranged in series or in parallel. The actuator may be used without a mixer to induce flow within the container. The actuator may be driven pneumatically, hydraulically, electrically, and/or in any other suitable manner.
B01F 31/55 - Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being contained in a flexible bag submitted to periodical deformation
B65D 83/00 - Containers or packages with special means for dispensing contents
B01F 31/441 - Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement performing a rectilinear reciprocating movement
B01F 35/513 - Flexible receptacles, e.g. bags supported by rigid containers
B01F 31/44 - Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement
B65D 75/36 - Articles or materials enclosed between two opposed sheets or blanks having their margins united, e.g. by pressure-sensitive adhesive, crimping, heat-sealing, or welding one or both sheets or blanks being recessed to accommodate contents one sheet or blank being recessed and the other formed of relatively stiff flat sheet material, e.g. blister packages
Kirigami mixing systems and related methods are generally described. In some embodiments, a mixing system includes one or more grippers configured to deform a portion of a flexible container containing fluid when undergoing axial deformation. The grippers may include features including slots, hinges, and spines to aid in the transition of the grippers between a closed and retracted configuration when the one or more grippers are deformed. The compression of the container subsequently result in fluid flow within the container which may mix or agitate the fluid. In some embodiments, the described grippers may be formed integrally with the flexible containers. In some embodiments, the mixing system may include a plurality of grippers arranged around the flexible container.
B01F 31/55 - Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being contained in a flexible bag submitted to periodical deformation
Different types of plastics (4, 7, 10), present in biologically contaminated products (20) of heterogenous composition, are separated based on specificities regarding melt viscosity and/or melting temperature, preferably using at least one melt filter. In a pre-processing unit (50), the solid products are subjected to size reduction, to obtain size-reduced parts (2). After heating of at least the plastic materials contained in the size-reduced parts, a molten mixture is obtained, including two types of plastics having specific melt viscosities and/or melting temperatures that are different. Then, in a separation equipment typically including an extruder, at least one of the two types of plastics is selectively separated from the molten mixture, as unfiltered part relative to a melt filter, the unfiltered part essentially or only containing a type of polymer that is sterilized, preferably due to said heating, and collected in a collection container (5, 8, 11).
Different types of plastics (4, 7, 10), present in biologically contaminated filtering devices (20) of heterogenous composition, are separated based on specificities regarding melt viscosity and/or melting temperature, preferably using at least one melt filter. In a preprocessing unit (50), the solid products are subjected to size reduction, to obtain size-reduced parts (2). After heating of at least the plastic materials contained in the size-reduced parts, a molten mixture is obtained, including two types of plastics having specific melt viscosities and/or melting temperatures that are different. Then, in a separation equipment (150) typically including an extruder (100), at least one of the two types of plastics (4, 7, 10) is selectively separated from the molten mixture, as unfiltered part relative to a melt filter, so that the unfiltered part may be collected as valuable material in a collection container (5, 8, 11).
The present invention relates to a separation system for separating and purifying a target component, a method for separating and purifying a target component, and the use of a crossflow diafiltration unit for processing a target phase, which is obtained after separation of an aqueous two-phase system and contains a target component.
A smart single-use tube line assembly (10) for use in a unit operation of a bioprocess comprises at least one tube line (16, 18). The tube line (16, 18) includes a tube body (22) surrounding a lumen (24) through which a medium can flow. The tube line assembly (10) also comprises a functional element (12, 14) embedded in the tube body (22), the functional element (12, 14) being configured to perform an optical and/or electrical function. The tube line assembly (10) further comprises an interface (26) for coupling both the lumen (24) and the functional element (12, 14) of the tube line (16, 18) to another component. The tube line assembly (10) still further comprises a control unit for controlling the optical and/or electrical function.
The invention relates to technical solutions for monitoring or controlling bioprocesses by way of withdrawing discrete fluid samples from a reactor and performing on-line analysis of said sample using a fluidic manifold, for example, by means of a sensor based in particular on label-free biomolecular interaction analysis. The invention particularly relates to a system for measuring one or more analytes in discrete fluid samples from a vessel adapted to contain a fluid comprising one or more sensors (5) for the measurement of the analytes (53) in a contact volume of the fluid sample, an analysis module (65) comprising at least one main sampling line in fluidic connection with the vessel and one or more pumps in fluidic connection with said main sampling line(s) and adapted to selectively pump fluid from in the main sampling line away from the vessel, at least one fluid distribution tubing (30) in fluidic connection with the analysis module, a manifold (20) comprising a body (25), and in the body (25), for each sensor (5), one fluidic cell comprising one fluid distribution channel (21) and a collecting channel (22a, 22b) in fluidic communication with the fluid distribution channel (21), wherein the fluid distribution tubing (30) is fitted in the fluid distribution channel (21) so that it is emerging in the collecting channel (22) and so that the sensor (5) can be contacted with at least a drop (10) of the fluid sample emerging at the top of the fluid distribution tubing (30) as the contact volume or wherein the fluid distribution tubing (30) is fitted in the fluid distribution channel (21) in fluidic connection with a measurement well (40), so the measurement well (40) can be filled with the fluid sample to create the contact volume and the sensor (5) can be dipped in the contact volume for measurement, and wherein said collecting channels (22a, 22b) are plunging so the fluid sample is collected per gravity.
G01N 1/14 - Suction devices, e.g. pumpsEjector devices
G01N 1/18 - Devices for withdrawing samples in the liquid or fluent state with provision for splitting samples into portions
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
C12M 1/32 - Inoculator or sampler multiple field or continuous type
G01N 1/00 - SamplingPreparing specimens for investigation
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 1/10 - Devices for withdrawing samples in the liquid or fluent state
The invention is directed to a method for producing a bioproduct using a bioprocess installation (1 ), wherein the bioprocess installation (1) comprises an electronic process control (2) and a bioprocess unit (3), wherein the bioprocess unit (3) comprises a receptacle (4), a clarification unit (5) with a centrifuge (6) and a chromatography unit (8) with a chromatograph (10), wherein cell broth obtained from the receptacle (4) is being lead through the clarification unit (5) and the chromatography unit (8) sequentially in a liquid stream (9), wherein the clarification unit (5) with its centrifuge (6) is being operated in a centrifugation cycle comprising centrifugation steps, such as loading-, washing- and discharging-steps, wherein the chromatography unit (8) with its chromatograph (10) is being operated in a chromatography cycle comprising chromatography steps, such as equilibration-, loading-, washing-, elution- and regeneration¬ steps, It is proposed that particle depletion between the liquid stream section leaving the clarification unit (5) and the liquid stream section leaving the chromatography unit (8) is less than 10% in particle concentration and that the execution of the steps assigned to the centrifugation cycle and the execution of the steps assigned to the chromatography cycle are at least partly being synchronized with each other by the electronic process control (2) in synchronization routines (13) based on assigned synchronization strategies (14).
A device arrangement (10) for separation of cells from a culture medium in a bioprocess, especially in a biopharmaceutical process, comprises: a reservoir vessel (12) for the culture medium; a filtration module (16) having at least one membrane across which flow is possible; a feed conduit (24) that connects the reservoir vessel (12) to an unfiltrate inlet (18) of the filtration module (16) for supplying culture medium to the filtration module (16); a return conduit (26) that connects a retentate-side outlet (20) of the filtration module (16) to the reservoir vessel (12) for recycling retentate into the reservoir vessel (12); a filtrate conduit (28) connected to a permeate-side outlet (22) of the filtration module (16) for removal of filtrate; a first pump (30) for maintaining a recirculation flow; a backflush conduit (32) that leads to a permeate-side connection (33) and/or to the permeate-side outlet (22) of the filtration module (16) for feeding a flush liquid into the filtration module (16); and a second pump (34) for conveying the flush liquid into the filtration module (16). A method of separating cells from a culture medium (14) has the following steps: cultivating cells in a culture medium (14) in a bioreactor; filtering the culture medium (14) in a filtration module (16) having at least one membrane, wherein the culture medium (14) passes through a recirculation circuit; flushing the membrane with a flush liquid during the filtering, wherein the flush liquid is a buffer solution or water or substrate, and wherein the flushing introduces flush liquid into the recirculation circuit, especially in order to dilute the recirculating unfiltrate and simultaneously to clean the membrane of the filtration module (16) by detaching the covering layer deposited on the membrane in the course of the filtration.
The invention relates to a product for providing membrane elements, comprising: a carrier film; and a membrane film, at least comprising: a support layer; and a membrane layer; the membrane film is releasably coupled to the carrier film; and the membrane film has a plurality of substantially discrete membrane elements. The invention also relates to a corresponding manufacturing process.
The invention relates to a method and a module for sterility testing based on optically analyzing at least one test liquid (3), which test liquid (3) is contained in a liquid container (4), wherein depending on the contamination state of the test liquid (3), non liquid contaminants (5) are distributed in the test liquid. It is proposed, that in an analyzing routine (9) performed by a control arrangement (6), image-related data (10) representing at least one optical image (I) of the test liquid (3), generated by a sensor arrangement (11), are being transmitted from the sensor arrangement (11) to the control arrangement (6) and the contamination state of the test liquid (3) is derived from the image-related data (10) based on the interrelation between the distribution characteristics of the contaminants (5) and the respective contamination state.
Systems and methods for characterizing a plurality of particles suspended in a solution are described. In some embodiments, an ultrasonic interrogation signal may be emitted into a solution including a plurality of particles suspended in the solution. A resulting ultrasonic spectrum may be sensed and provided to a trained statistical model of the solution. The trained statistical model may then determine one or more properties of the plurality of particles.
The invention relates to a device for a continuous virus inactivation during a protein production process, comprising a first and a second fluid inlet (2, 3), each of which is designed to introduce a liquid flow into the device (1), comprising a first mixer (4), which is designed to mix a liquid flow, and comprising a fluid outlet (5), which is designed to discharge a liquid flow out of the device (1), wherein a first liquid flow (6) which contains a target protein can be introduced into the device (1) by the first fluid inlet (2) and can be combined with a second virus-inactivating liquid flow (7), which can be introduced into the device (1) by the second fluid inlet (3), in a precisely defined volume ratio in order to form a third reactive liquid flow (8) which is conducted through the first mixer (4) for mixing purposes in order to generate defined virus-inactivating conditions. According to the invention, the device (1) has a head part (9) for combining two liquid flows, one of which is the liquid flow (6) containing the target protein; the device (1) has a dwell time assembly (10), which is fluidically connected to the head part (9), downstream of the first mixer (4) and upstream of the fluid outlet (5) in order to provide a minimum dwell time of the third reactive liquid flow (8) within the device (1); the head part (9) and the dwell time assembly (10) are rigidly secured to each other; and end face of the head part (9) is arranged on the dwell time assembly (10).
C12M 1/00 - Apparatus for enzymology or microbiology
B01F 25/42 - Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
B01F 25/43 - Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
The invention is directed to a method for operating a bioprocess installation (1) with an electronic process control (2) and at least one bioprocess unit (3), wherein the bioprocess unit (3) comprises a cell broth source with a first receptacle (4) for cell broth including cultivation media and cells, establishing a culture environment (A, B) for cell cultivation and/or bio production, wherein the bioprocess unit (3) comprises a clarification setup (5) with a centrifuge (6) for the clarification of the cell broth by centrifugation, with a liquid pumping arrangement (7) assigned to the centrifuge (6) and with a liquid network (8) with a number of liquid lines (9) communicating with the liquid pumping arrangement (7), wherein out of a first culture environment (A) established by the first receptacle (4), the cell broth is transfered to the centrifuge (6) via the liquid network (8), which centrifuge (6) is operated in a forward operation for cell separation and/or cell washing and in a backward operation for cell discharging. It is proposed that the liquid network (8) comprises a recycling line (15) and that in the backward operation, at least part of the discharged cells are being transferred into a second culture environment (B) different from the first culture environment (A) via the recycling line (15) for subsequent cell cultivation and/or bioproduction.
The present disclosure relates to a method of measuring cell density in a cell suspension comprising cell aggregates, the method comprising (i) Measuring the permittivity of the cell suspension; (ii) Comparing the measured permittivity with a predetermined value that is indicative of the cell density, thereby determining the cell density. Further described is a of a permittivity probe for determining the cell density of a suspension cell culture comprising cell aggregates.
G01N 33/487 - Physical analysis of biological material of liquid biological material
G01N 27/22 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating capacitance
98.
METHOD OF CHANGING CULTURE MEDIUM OF A CULTURE USING SPINFILTERS
The present invention relates to a method of expanding stem cells cultured as cell aggregates in a suspension culture changing culture medium and a method of medium exchange for the same cells characterized in the use of a rotating mesh such as a spinfilter device. The present invention further relates to a use of a rotating mesh for medium exchange in a suspension culture of stem cells.
A device assembly for controlling an integrated continuous pharmaceutical or biopharmaceutical manufacturing process comprises: a first process equipment (10) adapted for performing a first process step; a second process equipment (20) adapted for performing a second process step subsequent to the first process step; a single measuring unit (24) adapted for measurement of at least one set of signals of a liquid process medium at a single location, the set of measured signals depending on at least a first parameter and a different second parameter; and an evaluation and control unit (28) adapted for evaluating the set of measured signals to determine a value of the first parameter and a value of the second parameter. The evaluation and control unit (28) is further adapted for determining a first corrective feedback based on the value of the first parameter and a different second corrective feedback based on the value of the second parameter. The evaluation and control unit (28) is further adapted for controlling the first process step by providing the first corrective feedback to the first process equipment (10) and for controlling the subsequent second process step by providing the second corrective feedback to the second process equipment (20).
Summarizing the invention, a method for testing integrity of a filter is provided. The method comprises: pressurizing an upstream side of the filter to a test pressure; performing a check step comprising: - determining a flow rate of fluid from the upstream side to a downstream side of the filter; - comparing the determined flow rate with a flow range including a flow threshold; - setting stop criteria based on the comparison, wherein the stop criteria comprise at least one quantitative constraint indicative of a reliability of the determined flow rate and wherein: if the determined flow rate is within the flow range, the stop criteria are set to first stop criteria; and if the determined flow rate is outside the flow range, the stop criteria are set to second stop criteria; - determining whether the stop criteria are satisfied; if the stop criteria are not satisfied, repeating the check step until the stop criteria are satisfied; if the stop criteria are satisfied, comparing the determined flow rate with the flow threshold: if the determined flow rate is greater than or equal to the flow threshold, determining that the filter is non-integral; and if the determined flow rate is less than the flow threshold, determining that the filter is integral.
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