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 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).
Method for operating a bioprocess installation for production of a bioproduct, wherein the bioprocess installation comprises a source receptacle for cell cultivation, a harvest receptacle for bioproduction and a clarification setup with a centrifuge wherein the source receptacle is operated in a cyclical production mode comprising the steps of: a) starting the cyclical production mode, b) cultivating the cells thereby obtaining a cell broth comprising cultivated cells, c) discharging a discharge fraction of the cell broth, d) combining a restart fraction of the cell broth with fresh cultivation medium and repeating step b), e) repeating steps c) and d) at least once and/or f) discharging the cell broth obtained from step d), obtaining a discharge fraction, wherein the method further comprises the steps: i) centrifuging the discharge fraction via the centrifuge, ii) operating the harvest receptacle in a production mode, wherein steps i) and ii) are executed at least twice.
A method for the dynamic inline mixing of a pressurized medium containing a liquid and at least one further liquid or solid constituent in a bioprocess arrangement, the liquid being merged with the at least one further liquid or solid constituent in a predefined volume ratio at an opening point to form a resulting liquid flow, the bioprocess arrangement having a pump arrangement with a first pump, the first pump being arranged in the line of the line arrangement, the first pump being designed as a rotary pump configured for the dynamic inline mixing of the medium, the first pump having a liquid inlet, which during intended operation forms the suction side of the pump, and a liquid outlet, which during intended operation forms the pressure side of the pump, and the medium being conducted through the rotary pump for the purpose of dynamic inline mixing.
B01F 25/00 - Flow mixersMixers for falling materials, e.g. solid particles
B01F 35/213 - Measuring of the properties of the mixtures, e.g. temperature, density or colour
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
5.
FILTER MODULE, METHOD OF PRODUCING THE SAME, AND USE THEREOF
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.
A bioreactor system for carrying out a biological process including a vessel for receiving a liquid biological medium, and a gassing installation for controlled supply of different gases from gas sources into the vessel. The gassing installation has a plurality of gas outlet lines which open into gassing devices and/or into an overlay gas outlet in the interior of the vessel. Each gas outlet line is connected to a plurality of gas sources via a respective gas supply line or via a respective branch from a gas supply line. A mass flow controller connected to a controller is arranged in each gas supply line and in each branch. The system may include a controller with a master controller for a controlled variable, at least one sensor associated with the master controller, and one or more slave controllers having actuators, the manipulated variables of which purposefully influence the controlled variable.
A bioprocess system for a bioprocess operation with a display arrangement, wherein the bioprocess system comprises system components comprising at least one monitored system component, wherein the system components can be assembled into an assembled state in which the bioprocess system is operational for the bioprocess operation and can be disassembled into a disassembled state in which the bioprocess system is not operational for the bioprocess operation, The bioprocess system comprises a control arrangement and the display arrangement comprises at least one display component. In an assembled state of the bioprocess system during a bioprocess operation the control arrangement displays process information via the display arrangement and/or wherein during assembly of the bioprocess system the control arrangement displays assembly information via the display arrangement, wherein the process information and/or the assembly information concern at least the monitored system component and the display arrangement comprises at least one display component.
A sensor holding device holds a sensor device and includes a holding body configured for holding the sensor device and the holding body includes 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 that is moveable relative to the holding body to a first position and to a second position.
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 39/16 - Other self-supporting filtering material of organic material, e.g. synthetic fibres
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
A modular system for providing a bioprocess device assembly including a rigid skid and grid-modules. The skid includes identical plug-in structures arranged in a regular two-dimensional grid. The grid arrangement defines two-dimensional plug-in fields. At least some of the grid-modules have a matching counterpart plug-in structure. At least some of the grid-modules, in an installed state, have a two-dimensional extension in the plane of the grid that is not greater than a standard size of the plug-in fields. At least some of the grid-modules include a connection port to receive a rigid universal flow connector of standard shape and size in a standard position and orientation. At least some of the grid-modules have an integrated fluid line through which a medium to be processed or analyzed can flow. The integrated fluid line is in flow communication with the connection port of the grid-module. The grid-modules includes a flow control grid-module.
A device assembly for calibrating a single-use sensor before, during or after a biopharmaceutical manufacturing process step including 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 through which a medium flows in a defined direction during the process step and an integrated single-use sensor for measuring or detecting a property at a measurement location in the flow line. The device assembly includes a calibration line and a switch inserted into the flow line upstream of the measurement location. The switch includes a flow line inlet, a flow line outlet, and a calibration line inlet connected to the calibration line. The switch selectively switches between a first (main) flow path and a second (calibration) flow path. The device assembly includes a dedicated reference sensor, reference source, or reference standard solution in the calibration line.
G01N 21/31 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
G01N 1/14 - Suction devices, e.g. pumpsEjector devices
12.
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 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 at a first measurement location upstream of the purification unit; measuring the at least one parameter with a second measurement system at a second measurement location downstream of the purification unit; 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
A device 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 conducted by the line has a first and a second connection, and a measurement region arranged between the first connection and the second connection. The first connection, the measurement region, and the second connection define a flow path for the fluid through the device, and a flow-influencing element arranged in and/or on the flow path is configured to cause fluid flowing into the device via the first connection with a substantially laminar flow to have a substantially turbulent flow in the measurement region.
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 15/18 - Supports or connecting means for meters
14.
APPLICATION OF PERMITTIVITY MEASUREMENT PROBES IN AN SUSPENSION CULTURE AGGREGATE COMPRISING CELL AGGREGATES
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 27/02 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance
G01N 27/22 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating impedance by investigating capacitance
15.
SYSTEM FOR DETECTING A MEASUREMENT VARIABLE OF A FLUID 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
A system for detecting a measurement variable of a fluid being conducted in a fluid-conducting line, having a flowmeter for detecting the measurement variable, a flow-through device for arranging on the fluid-conducting line and for attaching the flowmeter. The flowmeter has a first and second connection and a measurement region which is arranged between the first connection and the second connection and which can be coupled to the flowmeter. The first connection, the measurement region, and the second connection define a flow path for the fluid through the flow-through device.
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 15/18 - Supports or connecting means for meters
16.
BIOREACTOR FOR CELL CULTURE WITH REUSABLE REACTOR VESSEL AND OPTICAL SPECTROSCOPY INTERFACE
A bioreactor for cell cultivation including a reusable reactor vessel, preferably made of stainless steel, for receiving a fluid, and an optical spectroscopy interface including an adapter and a single-use optical spectroscopy insert. The reusable reactor vessel has a wall and a port formed in the wall. The adapter is configured to be fixed to the port in a predefined position at the port. The single-use optical spectroscopy insert is configured to be accommodated and fixed in the adapter, or the insert is an integral part of the adapter.
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12M 1/00 - Apparatus for enzymology or microbiology
G01N 21/31 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
17.
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 for connecting a loop, preferably a tangential flow filtration loop or a sensor loop, to one port of a bioreactor, preferably a single-use bioreactor, is configured to be fixed to the port of the bioreactor. The multiport device includes a first flow path configured for withdrawing fluid from the bioreactor, and a second flow path configured for supplying fluid to the bioreactor. The first flow path has a first end adapted to be in fluid connection with the bioreactor, and a second end adapted to be connected to an inlet of the loop. The second flow path has an outer end adapted to be connected to an outlet of the loop, and a mouth adapted to be in fluid connection with the bioreactor. The mouth of the second flow path is distanced from the first end of the first flow path by at least 5 mm, preferably 10 mm.
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.
A separation system and methods for separating and purifying a target component include 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 15/14 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the introduction of the feed to the apparatus
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
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.
A bioreactor having a filter unit and a method for treating a cell broth. The filter unit has a supply channel (2), a first filter medium (4), a retentate channel (1), a second filter medium (5) and a permeate channel (3), arranged so that the first filter medium delimits the supply channel and the retentate channel from one another; and the second filter medium delimits the retentate channel and the permeate channel from one another. The supply channel is connected to an inlet for a supply medium; the retentate channel is connected to an inlet for a cell broth and to an outlet for the cell broth; the permeate channel is connected to an outlet for a permeate; and the interior of the bioreactor is connected to the inlet for the cell broth and to the outlet for the cell broth.
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
B01F 35/513 - Flexible receptacles, e.g. bags supported by rigid containers
23.
Flow-through centrifuge and method for bringing about an operational state of a flow-through centrifuge
The invention relates to a flow-through centrifuge which is used, for example, for biotechnical applications, in particular as a blood centrifuge. A driving arrangement and/or transmission arrangement of the flow-through centrifuge comprises a planetary gearset. In the planetary gearset, at least one planetary belt pulley is rotatably supported on a rotating planet carrier. A torque of the planetary belt pulley is transmitted via a belt. The planet carrier and the planetary belt pulley are driven at different rotational speeds. According to the invention, the planet carrier is held by a belt tensioning unit rotating with the planet carrier. A distance of the planet carrier from a rotor axis can be changed via the belt tensioning unit in order to adjust the belt tension of the belt.
F16H 9/26 - Gearings for conveying rotary motion with variable gear ratio, or for reversing rotary motion, by endless flexible members with members having orbital motion
24.
Valve switching system for selectively interconnecting components of a bioprocess installation
A valve switching system for selectively interconnecting components of a bioprocess installation, comprising a valve switching cassette and an actuator block. It is proposed, that the valve switching cassette comprises a perforated sandwich plate with perforation holes, which sandwich plate is placed between the cassette manifold and the actuator block body.
B01D 15/18 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
F16K 11/22 - Multiple-way valves, e.g. mixing valvesPipe fittings incorporating such valvesArrangement of valves and flow lines specially adapted for mixing fluid with two or more closure members not moving as a unit operated by separate actuating members with an actuating member for each valve, e.g. interconnected to form multiple-way valves
F16K 31/126 - Operating meansReleasing devices actuated by fluid the fluid acting on a diaphragm, bellows, or the like
25.
METHOD OF OPERATING A BIOPROCESS ARRANGEMENT TO PERFORM AT LEAST ONE REPETITION OF A BIOPROCESS
A method of operating a bioprocess arrangement to perform repetition of a bioprocess, wherein the bioprocess arrangement comprises a replaceable electronic component, wherein a process control system controls the bioprocess arrangement, using a digital model. The replaceable electronic components are removed and replaced by new electronic components, the process control system automatically detects the removal of the electronic components, automatically detects the presence of the new electronic components and retrieves digital representations of the new components, the process control system derives from the digital representations of the replaceable components and the new components a functional relationship, the process control system replaces the digital representations of the replaceable components with the digital representations of the new components based on the functional relationship thereby updating the digital model, and, that the process control system controls the bioprocess arrangement to perform the bioprocess based on the updated digital model.
A method for validating a filter unit. The method includes 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. The measurement area the fluid is exposed to is at least one alternating electric field between at least two electrodes. The method includes obtaining at least one electric signal between the at least two electrodes. 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. The method includes 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.
Various embodiments provide a method for producing a bioproduct using a bioprocess installation. The bioprocess installation comprises an process control and a bioprocess unit. The bioprocess unit comprises a receptacle, a clarification unit with a centrifuge and a chromatography unit with a chromatograph. Cell broth obtained from the receptacle is lead through the clarification unit and the chromatography unit in a liquid stream. The clarification unit with its centrifuge is being operated in a centrifugation cycle comprising centrifugation steps. The chromatography unit with its chromatograph is being operated in a chromatography cycle comprising chromatography steps. The particle depletion can be 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 process control in synchronization routines based on assigned synchronization strategies.
Systems and methods for characterizing a physical and solution properties of liquids are described. In some embodiments, an ultrasonic interrogation signal may be emitted into a liquid such as a solubilized protein 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 liquid. In some embodiments, the trained statistical model determines a viscosity of the liquid and/or a solubilized protein concentration of the liquid. In some embodiments, a trained statistical classification model configured to classify the liquid based, for example, on its contents or properties is used to improve modeling accuracy.
The invention relates to a centrifuge, in particular a continuous flow centrifuge, a biotechnical centrifuge or a blood centrifuge. The centrifuge comprises a refrigerant circuit. According to the invention, the outlet side of a controllable compressor is connected to an inlet side of an evaporator via a bypass line with a valve arranged therein. In a normal operation mode, a centrifuge vessel is cooled exclusively via the control of the compressor and an expansion unit while the valve is closed. If, on the other hand, a tolerance range of the target temperature in the centrifuge vessel is left, the valve is opened in order to bring about heating and thus a return of the temperature in the centrifuge vessel to the tolerance range.
A device assembly including a single-use device for sensing or influencing a parameter of a running bioprocess. The single-use device is configured to have at least two different defined functional states, a first functional state being an inactive delivery state in which the single-use device is sterile and inoperable according to its intended use, and a second functional state being an active use state in which the single-use device is operable according to its intended use. The device assembly further includes a signalling element for indicating a current functional state of the single-use device to a user. Each functional state is associated with a distinct signal. The device assembly is configured such that a transfer from the first functional state to any other functional state of the single-use device is irreversible and/or permanently prevents the signalling element from indicating the signal associated with the first functional state.
The disclosure relates to 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 way of a sensor based on label-free biomolecular interaction analysis. The disclosure relates to a system for measuring one or more analytes in discrete fluid samples from a vessel adapted to contain a fluid having one or more sensors for the measurement of the analytes in a contact volume of the fluid sample. An analysis module having 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 in fluidic connection with the analysis module. A manifold has a body.
A membrane for microbiological analysis, a production method of a membrane for microbiological analysis, and the use of such membranes for microbiological analysis. Examples include a cellulose membrane for microbiological analysis that is impregnated with a non-ionic surfactant in an amount of from 100 ng/cm2 to 1.0 mg/cm2, with the membrane having a nominal pore size of from 0.20 μm to 0.80 μm, and a cumulative adsorption pore volume of less than 0.010 cm3/g.
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
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. The system includes an aqueous-two phase extraction unit for aqueous-two phase extraction of the fluid, a separation unit for separating a target phase, and a crossflow diafiltration unit.
A smart single-use tube line assembly for use in a unit operation of a bioprocess including at least one tube line. The tube line includes a tube body surrounding a lumen through which a medium can flow. The tube line assembly also includes a functional element embedded in the tube body, the functional element being configured to perform an optical and/or electrical function. The tube line assembly further includes an interface for coupling both the lumen and the functional element of the tube line to another component. The tube line assembly still further includes a control unit for controlling the optical and/or electrical function.
A clamping device for fluidically and mechanically connecting two hose barbs. The clamping device includes a seal and a locking mechanism, wherein the locking mechanism can be transferred from a mounting condition to an assembled condition. In the mounting condition, the hose barbs can be inserted into the clamping device, while in the assembled condition, those hose barbs are locked in place in a position in which free ends of the hose barbs face each other and a seal coaxially aligns and fluid-tightly connects the free ends.
F16L 33/22 - Arrangements for connecting hoses to rigid membersRigid hose-connectors, i.e. single members engaging both hoses with means not mentioned in the preceding groups for gripping the hose between inner and outer parts
F16L 33/18 - Arrangements for connecting hoses to rigid membersRigid hose-connectors, i.e. single members engaging both hoses characterised by the use of additional sealing means
36.
Method and system for testing the integrity of filters
A method for testing integrity of a filter can include pressurizing an upstream side of the filter to a test pressure and performing a check step that includes 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, and setting stop criteria based on the comparison.
A modular processing system (100) for biopharmaceutical processes includes (i) at least one first and at least one second processing unit (30, 32), which can be fluidically connected to each other; and (ii) at least one adapter plate (200), through which at least one fluid flow (14), flowing from the first processing unit (30) to the second processing unit (32), can flow. The adapter plate deflects the fluid flow between the first processing unit and the second processing unit at least partially; and/or controls the fluid flow, preferably, the pressure thereof, in an open loop or closed loop manner. A method for the modular construction of a processing system (100) for biopharmaceutical processes is also disclosed.
A device arrangement for separating cells from a culture medium in a bioprocess, in particular in a biopharmaceutical process, including a storage tank for the culture medium; a filtration module having a membrane adapted to be overflowed; an intake line connecting the storage tank to an unfiltrate inlet for supplying culture medium into the filtration module; a return line which connects a retentate-side outlet of the filtration module to the storage tank for returning retentate into the storage tank; a filtrate line which is connected to a permeate-side outlet of the filtration module for discharging filtrate; a first pump for maintaining a recirculation circuit; a backflush line which leads to a permeate-side connection and/or to the permeate-side outlet for supplying a rinsing liquid into the filtration module; and a second pump for conveying the rinsing liquid into the filtration module. A method of separating cells from a culture medium.
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.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B32B 3/30 - Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shapeLayered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layerLayered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shapeLayered products comprising a layer having particular features of form characterised by a layer with cavities or internal voids characterised by a layer formed with recesses or projections, e.g. grooved, ribbed
B32B 7/06 - Interconnection of layers permitting easy separation
B32B 7/12 - Interconnection of layers using interposed adhesives or interposed materials with bonding properties
B32B 23/06 - Layered products essentially comprising cellulosic plastic substances comprising such substance as the main or only constituent of a layer, next to another layer of a specific substance of paper or cardboard
B32B 23/08 - Layered products essentially comprising cellulosic plastic substances comprising such substance as the main or only constituent of a layer, next to another layer of a specific substance of synthetic resin
B32B 27/08 - Layered products essentially comprising synthetic resin as the main or only constituent of a layer next to another layer of a specific substance of synthetic resin of a different kind
B32B 27/10 - Layered products essentially comprising synthetic resin as the main or only constituent of a layer next to another layer of a specific substance of paper or cardboard
B32B 27/28 - Layered products essentially comprising synthetic resin comprising copolymers of synthetic resins not wholly covered by any one of the following subgroups
B32B 37/12 - Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by using adhesives
B32B 37/18 - Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by the properties of the layers with all layers existing as coherent layers before laminating involving the assembly of discrete sheets or panels only
B32B 38/10 - Removing layers, or parts of layers, mechanically or chemically
Embodiments include a device for continuous virus inactivation during a protein production process comprising a first and a second fluid inlet, a first mixer, and a fluid outlet. A first liquid stream containing a target protein is introducible into the device through the first fluid inlet and is combinable in a predefined volume ratio with a second, virus-inactivating liquid stream introducible into the device through the second fluid inlet to form a third, reactive liquid stream which is conducted through the first mixer for mixing in order to generate predefined, virus-inactivating conditions. The device further comprises a head part and, downstream of the first mixer and upstream of the fluid outlet, a residence time arrangement fluidically connected to the head part for provision of a minimum residence time of the third stream, wherein the head part and the residence time arrangement are rigidly fastened to each other.
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.
A method for operating a bioprocess installation with an electronic process control and at least one bioprocess unit, wherein the bioprocess unit comprises a cell broth source with a first receptacle for cell broth including cultivation media and cells, establishing a culture environment for cell cultivation and/or bio production, wherein the bioprocess unit comprises a clarification setup with a centrifuge for the clarification of the cell broth by centrifugation, with a liquid pumping arrangement assigned to the centrifuge and with a liquid network with a number of liquid lines communicating with the liquid pumping arrangement, wherein out of a first culture environment established by the first receptacle, the cell broth is transfered to the centrifuge via the liquid network, which centrifuge is operated in a forward operation for cell separation and/or cell washing and in a backward operation for cell discharging.
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 including a first process equipment for performing a first process step; a second process equipment for performing a second process step subsequent to the first process step; a single measuring unit for measurement of a set of signals of a liquid process medium at a single location, the measured signals depending on first and second parameters; and an evaluation and control unit for evaluating the measured signals to determine values of the first and second parameters. The evaluation and control unit determines first and second corrective feedback based on the values of the first and second parameters, respectively. The evaluation and control unit controls the first process step by providing the first corrective feedback to the first process equipment and controls the second process step by providing the second corrective feedback to the second process equipment.
A method for providing an integrity test of a double filter capsule can include providing the double filter capsule in such a way that in a filtration process the medium to be filtered flows in its flow direction from an upstream chamber in the housing through a first filter into an intermediate chamber between the first filter and a second filter and then through the second filter to an outlet. The housing can have an upstream-chamber access point for feeding a test fluid into the upstream chamber and an intermediate-chamber access point for feeding the test fluid into the intermediate chamber. Additional steps can include providing a connecting line between the upstream-chamber access point and the intermediate-chamber access point and determining the state of integrity of the double filter capsule on the basis of at least two test phases.
B01D 65/10 - Testing of membranes or membrane apparatusDetecting or repairing leaks
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
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
46.
Installation for biotechnological applications, with carrier for the mounting of components
A method for mounting at least one component on an installation includes attaching a carrier directly or indirectly to the installation, where the installation has at least one frame with at least two arms, at least one base plate, and at least one deformable element. The method further includes displacing the component toward the deformable element such that the deformable element is displaced from a receiving state (AUZ), in which the deformable element is ready to receive the component of the installation, toward a locked state (ARZ), as a result of which the deformable element surrounds and mounts the component of the installation at least in part.
The present invention relates to a chromatographic material comprising a polymer network material-based self-supporting bi-continuous separation matrix for adsorptive material separation in liquid media, and a method of producing the chromatographic material comprising a polymer network material-based self-supporting bi-continuous separation matrix.
B01J 20/24 - Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
B01J 20/30 - Processes for preparing, regenerating or reactivating
B01J 20/28 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof characterised by their form or physical properties
A method for ensuring a microbiological purity of a single-use device for carrying out a biotechnological process, the single-use device including at least one gamma-sterilizable component which is formed from materials suitable for a sterilization by gamma radiation, and at least one non-gamma-sterilizable subunit which contains a material unsuitable for a sterilization by gamma radiation. Both the component and the subunit each have an area that comes into contact with a process medium when the biotechnological process is carried out. The method includes the steps of sterilizing the gamma-sterilizable component by gamma radiation; protecting the medium-contacting area of the gamma-sterilizable component by a sterile barrier; sterilizing the non-gamma-sterilizable subunit with superheated steam; protecting the medium-contacting area of the non-gamma-sterilizable subunit by a sterile barrier; removing the sterile barriers; and mounting the gamma-sterilized component and the superheated steam-sterilized subunit in the single-use device immediately after removing the sterile barriers.
A computer-implemented method can configure and/or setup and/or control a downstream process for processing a biomass, including receiving at least one measurement value of at least one feature of an upstream process by which the biomass to be processed in the downstream process has been obtained and/or of at least one feature of a downstream process stage or operation, determining at least one downstream process parameter based on the received at least one measurement value, arid configuring and/or setup and/or controlling at least one downstream process stage or process operation based on the determined at least one downstream process parameter.
A chromatography system is provided. The chromatography system is configured to process a feed fluid containing a plurality of components, wherein at least one component of the plurality of components of the feed fluid is a target component. The chromatography system comprises: a flow path comprising a plurality of fluid control components configured to control a fluid flow; a stationary phase, wherein the stationary phase is at least one membrane adsorber connected to the flow path and the stationary phase is configured to isolate the target component. The flow path is configured such that harvesting of the target component is optimized.
B01D 15/24 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the treatment of the fractions to be distributed
B01D 15/12 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
B01D 15/14 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the introduction of the feed to the apparatus
Various embodiments relate to a digital control unit of a bioprocess arrangement for controlling a bioprocess, wherein the digital control unit comprises a local data storage and a local processor unit, wherein the digital control unit comprises a bioprocess interface for sending and receiving bioprocess control data, wherein the digital control unit is configured to execute a bioprocess control routine via the local processor unit to control the bioprocess, wherein in the bioprocess control routine, the digital control unit generates bioprocess data from the actuator data and/or the sensor data and/or the user control command data. It is proposed that the digital control unit is configured to execute a signing routine via the local processor unit and that in the signing routine, the digital control unit digitally signs documentation data, derived from the bioprocess data, by generating a digital signature.
H04L 9/32 - Arrangements for secret or secure communicationsNetwork security protocols including means for verifying the identity or authority of a user of the system
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
H04L 9/00 - Arrangements for secret or secure communicationsNetwork security protocols
The present invention relates to isolated nucleic acid molecules, comprising a functional mammalian EGR-1 (early growth response protein 1) promoter region that is operatively linked to a gene encoding a fluorescent protein and controls expression of said gene. The present invention further relates to nucleic acid vectors, comprising said nucleic, cells comprising said nucleic acids or vectors, being capable of sensing and indicating fluid shear stress acting on themselves, and methods of generating the same. Furthermore, the present invention relates to methods of evaluating fluid shear stress acting on cells in real-time during the operation of a biotechnological device or system, methods of evaluating a biotechnological device or system with respect to fluid shear stress acting on cells caused by operation of said device or system, and methods of designing a biotechnological device or system, said methods using said cells.
A distributor assembly, which is provided in particular for a separation unit of a modular process device arrangement, including a fluid distributor device having a plurality of fluid ports, wherein the fluid distributor device can selectively establish and block fluid communications between the fluid ports. The distributor assembly further includes a connecting element and a retaining element. The connecting element is adapted to be attached to one of the fluid ports, and the distributor assembly includes an associated mounting slot at the fluid port. The mounting slot is adapted to the shape of the retaining element such that the retaining element can be inserted into the mounting slot up to a defined retaining position, in which the retaining element engages the connecting element and fixes it in place.
A modular device for a fixed arrangement and interconnection of individual separation units and/or first functional units for performing one or more unit operations in a biotechnological process. The modular device includes a plurality of distributor caps provided for attachment to the separation units and/or first functional units. The distributor caps each have: a fluid distribution mechanism having a working connection and at least two supply or discharge connections, wherein the fluid distribution mechanism can assume at least two defined switching positions; connection mechanisms for establishing a flow communication between a fluid inlet or outlet of the separation unit or the first functional unit and the working connection of the fluid distribution mechanism; coupling mechanisms for establishing a rigid mechanical coupling and a flow communication with an adjacent distributor cap; and an interface for changing the switching positions of the fluid distribution mechanism.
B01D 29/90 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor having feed or discharge devices for feeding
A method for conducting a bioprocess with a digital control unit of a bioprocess arrangement, wherein the digital control unit comprises a local data storage and a local processor unit, wherein the digital control unit comprises a bioprocess interface for sending and receiving bioprocess control data, wherein bioprocess data are generated by the digital control unit, wherein a bioprocess control routine is executed by the local processor unit to control the bioprocess, wherein in the bioprocess control routine, the bioprocess data are generated by the digital control unit from actuator data and/or sensor data and/or user control command data. It is proposed that a signing routine is initiated by the local processor unit in the data safety routine to be executed by an external signing unit(s).
G05B 19/042 - Programme control other than numerical control, i.e. in sequence controllers or logic controllers using digital processors
H04L 9/32 - Arrangements for secret or secure communicationsNetwork security protocols including means for verifying the identity or authority of a user of the system
H04L 67/125 - Protocols specially adapted for proprietary or special-purpose networking environments, e.g. medical networks, sensor networks, networks in vehicles or remote metering networks involving control of end-device applications over a network
A method for conducting a bioprocess with a digital control unit of a bioprocess arrangement, wherein the digital control unit comprises a local data storage and a local processor unit, wherein bioprocess data are generated by the digital control unit. It is proposed, that in a data safety routine, a documentation routine and a signing routine are executed, that in the documentation routine, documentation data are generated from the bioprocess data and that in the signing routine, a cryptographic private key is extracted from private key data and the documentation data are digitally signed with the cryptographic private key by generating a digital signature and that the documentation routine is executed continuously during the bioprocess and that the signing routine is executed discontinuously during the bioprocess in several signing cycles according to a signing strategy, which defines trigger events for initiating the signing routine.
H04L 9/32 - Arrangements for secret or secure communicationsNetwork security protocols including means for verifying the identity or authority of a user of the system
H04L 9/00 - Arrangements for secret or secure communicationsNetwork security protocols
57.
BIOREACTOR SYSTEMS AND METHOD FOR OPERATING A BIOPROCESS
A bioreactor system for receiving a disposable bioreactor bag comprises a receiving container having a container wall which defines a receiving space in which the disposable bioreactor bag is received in an operating state of the bioreactor system. A stirring system projects at least partially into the receiving space and is designed and configured to stir a biomedium present in the disposable bioreactor bag in the operating state of the bioreactor system. At least one baffle, which makes the receiving space smaller and differs from the container wall, serves to reduce a laminar flow of the biomedium. A temperature control medium flows through at least part of the at least one baffle, said temperature control medium controlling the temperature of the baffle.
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/06 - Apparatus for enzymology or microbiology with gas introduction means with agitator, e.g. impeller
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
58.
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 for connecting a loop, preferably a tangential flow filtration loop or a sensor loop, to one port of a bioreactor, preferably a single-use bioreactor, is configured to be fixed to the port of the bioreactor. The multiport device includes a first flow path configured for withdrawing fluid from the bioreactor, and a second flow path configured for supplying fluid to the bioreactor. The first flow path has a first end adapted to be in fluid connection with the bioreactor, and a second end adapted to be connected to an inlet of the loop. The second flow path has an outer end adapted to be connected to an outlet of the loop, and a mouth adapted to be in fluid connection with the bioreactor. The mouth of the second flow path is distanced from the first end of the first flow path by at least 5 mm, preferably 10 mm.
A fluid processing system includes a fluid processing unit and a tubing arrangement providing fluid flow to and from the fluid processing unit. The tubing arrangement includes one or more flow cells and the fluid processing unit is selected from a unit comprising a single use tangential flow filtration mobile skid and a unit comprising a device for chromatographic separation. Each one of the flow cells includes a body having an inlet and an outlet and a fluid flow channel extending from the inlet to the outlet of the body.
A filtering system (10) includes a filtering apparatus having a filter unit for receiving liquid to be filtered, a receptacle for receiving filtered liquid, and an adapter (14) for coupling the filter unit to the receptacle, and also includes a base (12) having a cradle (26) for receiving the filtering apparatus and a base vacuum delivery port (28). The adapter includes an adapter vacuum receiving port (22) coupled to the vacuum delivery port for driving the liquid through the filter and—as filtered liquid—into the receptacle. The cradle and the adapter have an interlocking mechanism (52, 54) that locks the filtering apparatus to the cradle in a locking position in which the vacuum receiving port is sealingly coupled to the base vacuum delivery port. The base vacuum delivery port has a vacuum valve (30) constituted as a normally-closed valve automatically forced open when the filtering apparatus locks to the cradle.
A valve block for single use in a bioprocess, having a plurality of valve units and a one-piece block body having a main conduit. Each valve unit includes a secondary conduit, a valve seat between the secondary conduit and the main conduit, a closure part having a gripping portion, and an actuator coupled to the gripping portion which can transfer the closure part from a first switching position, in which the closure part is pressed against the valve seat and blocks a fluid communication between the secondary conduit and the main conduit, to a second switching position, in which the closure part is lifted from the valve seat and unblocks the fluid communication between the secondary conduit and the main conduit. The gripping portion is sealed against both the main conduit and the secondary conduit in both switching positions of the valve unit.
F16K 11/22 - Multiple-way valves, e.g. mixing valvesPipe fittings incorporating such valvesArrangement of valves and flow lines specially adapted for mixing fluid with two or more closure members not moving as a unit operated by separate actuating members with an actuating member for each valve, e.g. interconnected to form multiple-way valves
F16K 27/00 - Construction of housingsUse of materials therefor
62.
AUTOMATED CENTRIFUGE SETUP OF A BIOPROCESSING INSTALLATION
A centrifuge setup of a bioprocessing installation, wherein, for the centrifugation, the centrifuge setup comprises a centrifuge, wherein the centrifuge comprises at least one centrifuge chamber with a chamber inlet and a chamber outlet, wherein the centrifuge setup comprises a liquid pumping arrangement and a liquid network with a number of liquid lines communicating with the liquid pumping arrangement. The centrifuge setup comprises a sensor arrangement with at least one biomass sensor arrangement, which biomass sensor arrangement is assigned to a liquid line of the liquid network, that the process control calculates an occurrence level of biomass in the respective liquid line based on the sensor signals of the biomass sensor arrangement and that the process control controls the valve arrangement and/or the liquid pumping arrangement during the loading cycle and/or the washing cycle and/or the discharging cycle based on the sensor signals of the sensor arrangement.
A device assembly for producing bioconjugates, in particular antibody-drug conjugates, including a conjugation unit for performing a bioconjugation reaction in a medium, a first filtration unit for separating precipitates and/or agglomerates, and a second filtration unit for performing an ultrafiltration and/or a diafiltration process. The first filtration unit is arranged in a flow path between the conjugation unit and the second filtration unit. The device assembly further includes a single control unit for controlling the transfer of medium from the conjugation unit through the first filtration unit to the second filtration unit and for controlling the ultrafiltration and/or diafiltration process.
Fluidic modules configured for flowing fluid through membranes and associated methods are generally provided. In some embodiments, a fluidic module comprises two channels between which a membrane is positioned. The two channels may have geometries such that the pressure drop experienced by a fluid flowing from the first channel, through the membrane, and into the second channel is substantially independent of the location along the channel at which it flows through the membrane. In other words, the pressure drop may be substantially constant over the membrane area.
A clarification setup of a bioprocessing installation wherein, for the centrifugation, the clarification setup comprises a centrifuge, wherein the centrifuge comprises at least one centrifuge chamber with a chamber inlet and a chamber outlet, wherein the clarification setup comprises a liquid pumping arrangement assigned to the centrifuge and a liquid network with a number of liquid lines communicating with the liquid pumping arrangement, wherein the clarification setup comprises a process control for controlling the centrifuge and the liquid pumping arrangement. For filtration, the clarification setup comprises a filter arrangement, that the liquid network provides an outlet supernatant line for a liquid connection between the chamber outlet and the filter arrangement, which is at least temporarily liquid-tight, such that due to this liquid-tight condition of the outlet supernatant line the liquid pumping arrangement as such may drive the supernatant from the chamber outlet to the filter arrangement.
A sparging device, especially for use in a bioprocess, including a medium chamber and at least one gas chamber. The gas chamber at least partially surrounds the medium chamber, or the medium chamber at least partially surrounds the gas chamber. The medium chamber and the gas chamber are separated from each other by a wall. The wall has a plurality of through-holes or is composed of a porous material, such as a membrane or a porous ceramic. The sparging device further includes at least one gas inlet port opening into the gas chamber for inflow of gas.
C12M 1/00 - Apparatus for enzymology or microbiology
B01F 23/232 - Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using flow-mixing means for introducing the gases, e.g. baffles
B01F 25/314 - Injector mixers in conduits or tubes through which the main component flows wherein additional components are introduced at the circumference of the conduit
67.
Safety device for a single-use mixing or storage system
A safety device for a single-use mixing or storage system (10), especially for use in a biopharmaceutical process, includes a flexible bag (12) made from a film material and a support structure (14) receiving and supporting the bag (12) in several directions. The support structure (14) allows an expansion of the bag (12) in an expansion direction. The safety device further includes a detection unit (20) adapted to detect an expansion of the bag (12) in the expansion direction, and a control unit (28) connected to the detection unit (20) and adapted to initiate a safety measure in response to the expansion of the bag (12) in the expansion direction that exceeds a given threshold.
Stitftung für Lasertechnologien in der Medizin und Me technik an der Universität Ulm (Germany)
Inventor
Nothelfer, Steffen
Kienle, Alwin
Foschum, Florian
Hoehse, Marek
Abstract
Devices and methods are provided for determining viability and/or a cell counts of biological cells in a cell suspension culture using collimated transmission. Devices can include an illumination source for generating an electromagnetic illumination beam; beam manipulation means for collimating the illumination beam; and a detection unit for detecting an electromagnetic transmission beam being a portion of the collimated illumination beam which has been transmitted through a sample of the cell suspension culture.
Various embodiments relate to an aeration device for a bioprocessing installation, in particular a bioreactor, comprising a housing, wherein the housing comprises one or more aeration channels in its interior, wherein the housing further comprises one or more gas inlet ports, via each of which a gas can be introduced into at least one aeration channel of the housing, and wherein the housing further comprises a plurality of gas outlet ports, via each of which the gas can be discharged from the respective aeration channel to the outside of the aeration device. It is proposed that the aeration device is configurable with respect to a predetermined discharge of gas via the gas outlet ports.
A flow cell assembly for use in a bioprocess including a housing and a glass body. The housing includes an inlet tube connector and an outlet tube connector and a holding structure for immovably holding the glass body. The glass body is a universal single-piece glass body surrounding a measurement channel. The measurement channel has an inlet end and an outlet end defining a medium flow direction, and a defined dimension along an optical measurement axis perpendicular to the medium flow direction. The inlet end and outlet end of the measurement channel are in fluid communication with the inlet tube connector and the outlet tube connector of the housing, respectively. The housing or the glass body includes an aligning structure for aligning a probe head. The housing or the glass body includes a fixing structure for immovably fixing the aligned probe head relative to the glass body.
The present invention relates to a filtration unit with a filtration membrane, nutritive cardboard disc and, if necessary, a support structure, wherein the nutritive cardboard disc and/or the support structure comprises a solid, water-soluble nutrient medium and a water-soluble and/or water-swellable polymer, a method for producing the filtration unit, a method for detecting microorganisms in a fluid, wherein the filtration unit is used, and the use of the filtration unit for detecting microorganisms in a fluid.
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
System for detecting at least one presence of foam of a medium in a bioreactor plant, wherein the system comprises: —a bioreactor plant having at least one disposable container for receiving the medium that may comprise the foam; and—at least two capacitive sensor units which are attached at at least two different situating positions of the bioreactor plant, wherein the capacitive sensor units each comprise at least one electrode system for capacitive measurement and are able to detect the presence of foam at the at least two situating positions on the basis of the capacitive measurement; and wherein the capacitive sensor units are designed to transmit captured data relating to the presence of foam to at least one monitoring unit for monitoring, open-loop and/or closed-loop control of foam formation in the bioreactor plant on the basis of said data.
C12M 1/00 - Apparatus for enzymology or microbiology
G01D 5/24 - Mechanical means for transferring the output of a sensing memberMeans for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for convertingTransducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage by varying capacitance
G01F 23/26 - Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm by measuring physical variables, other than linear dimensions, pressure or weight, dependent on the level to be measured, e.g. by difference of heat transfer of steam or water by measuring variations of capacity or inductance of capacitors or inductors arising from the presence of liquid or fluent solid material in the electric or electromagnetic fields
H03K 17/955 - Proximity switches using a capacitive detector
73.
FILTRATION MODULE AND ASSEMBLY FOR FILTERING A PROCESS MEDIUM IN A BIOPROCESS AND METHOD OF SAMPLING DURING A BIOPROCESS
A filtration module for filtering a process medium in a bioprocess including a process flow path for a process medium, a filter membrane coupled to the process flow path, and a sampling membrane coupled both to the process flow path and to a sampling flow path for extracting a sample from the process medium. The sampling flow path guides the extracted sample to a sampling outlet of the filtration module or to an analyzer integrated into the filtration module. A filtration assembly including the filtration module and an analyzer coupled to the sampling outlet of the filtration module. A method of sampling during a bioprocess including providing such a filtration module, urging a process medium through the process flow path, filtering the process medium by using the filter membrane, extracting a sample from the process medium by using the sampling membrane, and guiding the extracted sample to a sampling outlet.
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
74.
Open-loop/closed-loop process control on the basis of a spectroscopic determination of undetermined substance concentrations
Method for open-loop or closed-loop control of a process, in particular a downstream bioprocess, based on the projection of an unknown concentration of at least one substance in a sample using spectroscopy, in particular UV/vis spectroscopy, comprising the steps: Detect spectrums of a plurality of concentration samples, wherein at least two concentration samples have differing concentrations of the substance; generate several quantitative models based on the spectrums of the concentration samples, wherein the models each have a mapping of at least one spectral measurand of the spectrums to concentrations in concentration ranges, wherein the concentration ranges of two models are not identical; detect at least one sample spectrum of the sample; map the sample spectrum to at least one quantitative model of the generated quantitative models; apply the at least one quantitative model that was mapped to the sample spectrum against the sample spectrum to determine a projected value for the unknown concentration; and apply open-loop and/or closed-loop control of the process for at least one parameter based on the projected value for the undetermined concentration.
G01N 21/33 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
G01N 21/85 - Investigating moving fluids or granular solids
A bioprocessing installation comprising a reservoir tank, one or more fluid lines, one or more receiving containers and an electronic control unit. The fluid line fluidically connects the reservoir tank to a receiving container. The liquid biological medium can be transferred from the reservoir tank through the fluid line into the at least one receiving container. The bioprocessing installation comprises a sensor arrangement with at least one gas bubble sensor, which sensor arrangement is configured to detect one or more gas bubbles or foam or separated phases in the liquid biological medium by a gas bubble sensor and to generate one or more corresponding sensor signals, and the electronic control unit is configured to monitor the transfer of the liquid biological medium from the reservoir tank in the direction of the at least one receiving container based on the sensor signals generated by the sensor arrangement.
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
B65B 3/00 - Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans or jars
B65B 57/10 - Automatic control, checking, warning or safety devices responsive to absence, presence, abnormal feed, or misplacement of articles or materials to be packaged
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
76.
Single-use device for the separation or filtering of a large volume of a mixture of substances
A single-use device for separating or purifying a large volume of a mixture of substances including membrane chromatography modules which are fixedly mounted in a predetermined grid and a line system for linking the membrane chromatography modules and for connecting the membrane chromatography modules to each other. A cover or bottom mechanism holding the membrane chromatography modules in position in a predetermined grid may be attached to the upper or lower side of the membrane chromatography modules. At least part of the line system is formed in the cover or the bottom mechanism, with connecting lines between the membrane chromatography modules. In a method of separating or purifying a large volume of a mixture of substances using such a single-use device having a plurality of automated valves and sensors connected to a control unit, the automated valves are controlled based on an evaluation of the parameters measured by the sensors.
B01D 15/18 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
B01D 15/12 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
B01D 29/52 - 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 parallel connection
B01D 29/60 - Filters with filtering elements stationary during filtration, e.g. pressure or suction filters, not covered by groups Filtering elements therefor integrally combined with devices for controlling the filtration
The present invention relates to a method of changing culture medium of a suspension culture, the suspension culture comprising cells suspended in the culture medium, the method comprising: (i) transferring a fraction of the suspension culture into a container, wherein the container comprises at least one opening at the bottom; (ii) allowing the cells comprised in the fraction of the suspension to settle at the at least one opening at the bottom of the container by gravitation, thereby forming a supernatant; (iii) dispensing the cells settled at the bottom of the container (back) into the suspension culture; (iv) discarding the supernatant.
The invention relates to a modular processing system for biopharmaceutical and/or chemical processes, comprising: at least one processing unit; at least one adapter plate, which can be directly or indirectly fluidically connected to the processing unit, wherein the adapter plate has at least one adapter channel, through which at least one fluid flow can flow to the processing unit, wherein the adapter plate also has at least one deflection element and/or a pump and/or at least one valve; and an external control device. The adapter plate is designed in such a way that the fluid flow to the processing unit can be at least partially deflected with the at least one deflection element in the adapter channel and/or the fluid flow, preferably its pressure, is controllable with the at least one valve and/or the pump in the adapter channel. A respective at least one sensor is embedded in the processing unit and/or in the adapter plate, in order to detect at least one property of the fluid flow in the processing unit or the adapter plate. The external control device can be coupled to the at least one sensor in such a way that measurement data of at least one sensor can be read out, and the fluid flow in the processing unit and or the adapter plate can be centrally controlled based on the read-out measurement data. The invention also relates to a method for centrally controlling a modular processing system for biopharmaceutical and/or chemical processes.
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 an improved diatomaceous earth composition containing salt water. The diatomaceous earth composition according to the present invention comprises an agglomerated mixture of calcined diatomaceous earth particles, water and at least one inorganic salt, wherein the mass ratio of the calcined diatomaceous earth particles and water is in the range of 1:1.0 to 1:2.0, and wherein the content of the at least one inorganic salt is equal to or more than 0.25 parts by mass based on 100 parts by mass of water. In a further aspect, the present invention relates to a method for producing the diatomaceous earth composition according to the present invention. In another aspect, the present invention relates to the use of the diatomaceous earth composition according to the present invention as an agent for precoat filtration or dynamic body feed filtration in biopharmaceutical applications.
B01J 20/02 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material
B01D 37/02 - Precoating the filtering elements or materialAddition of filter aids to the liquid being filtered
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
B01J 20/28 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof characterised by their form or physical properties
B01J 20/30 - Processes for preparing, regenerating or reactivating
C12M 1/00 - Apparatus for enzymology or microbiology
C12N 1/02 - Separating microorganisms from their culture media
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
81.
SYSTEM AND METHOD FOR THE GENERATION OF HIGH CELL DENSITY SEED CULTURE
A system for an automated production of high cell density seed culture, HCDC, preparations, for cryo-preservation comprising a cell expansion device for growing a HCDC in a medium inside a device volume of the cell expansion device, at least one sensor for collecting data by at least temporally monitoring at least one parameter being indicative of the physiological state of the HCDC; and a control unit for processing the collected data to determine whether at least one predetermined criterion is fulfilled by the monitored parameter to control, based on whether the at least one predetermined criterion is fulfilled by the monitored parameter, at least a partial exchange of the medium by a cryo-protective agent, CPA.
The invention relates to a sterile connector for the sterile transfer of a liquid medium, in particular a biological medium, from a liquid container (2) into a fluid chamber (3, 3), wherein the sterile connector (1) has a first coupling device (5) and a second coupling device (6). It is proposed that the first coupling device (5) has a fluid inlet (7) and a fluid outlet (8) and also a first cannula (9), the latter having an end which is directed away from the fluid inlet (7) and forms the fluid outlet (8), that the second coupling device (6) has a fluid passage (10) which, in an initial state of the sterile connector (1), is covered axially by a first septum (11), that the fluid outlet (8), in the initial state of the sterile connector (1), is arranged in a hermetically sealed region of the first coupling device (5) and the surface (11a) of the first septum (11) facing axially away from the fluid passage (10) is arranged in a hermetically sealed region of the second coupling device (6), and that, in a fluidic connection process starting from the initial state of the sterile connector (1), a fluidic connection between the fluid inlet (7) and the fluid passage (10) can be produced by the fact that the end of the first cannula (9) forming the fluid outlet (8) pierces the first septum (11) of the second coupling device (6).
Chromatography method, method of determining the concentration of at least one compound in a chromatography method, method of obtaining an adsorption isotherm, method of obtaining at least one stationary phase and method of evaluating the accuracy of a predetermined adsorption isotherm
The present invention relates to a chromatography method, a method of determining the concentration of at least one compound in a chromatography method, a method of obtaining an adsorption isotherm, a method of obtaining at least one stationary phase and a method of evaluating the accuracy of a predetermined adsorption isotherm.
A method for degassing a cross-flow diafiltration unit, a cross-flow diafiltration method and a cross-flow diafiltration unit. The degassing method includes (i) providing a cross-flow diafiltration unit having a diafiltration channel, a retentate channel and a permeate channel, a first filter material that delimits the diafiltration channel from the retentate channel, and a second filter material that delimits the retentate channel from the permeate channel; and thereafter (ii) feeding a liquid into the retentate channel so that the liquid flows in a flow direction through the retentate channel and penetrates through the first filter material into the diafiltration channel, whereby the retentate channel and the diafiltration channel are filled with and degassed by the liquid.
Chromatography method, method of determining the concentration of at least one compound in chromatography method and method of obtaining at least one chromatography method parameter
Chromatography methods, methods of determining the concentration of at least one compound in a chromatography method and methods of obtaining at least one chromatography method parameter are provided. The chromatography methods include performance based on results obtained from the methods of determining the concentration of at least one compound or methods of obtaining at least one chromatography method parameter.
b, which may vary due to the varying composition and/or temperature and which are determined for the varying composition of the mobile phase and/or the varying chromatography temperature.
The present invention relates to a method for producing a porous membrane, the method being characterized in that a solvent system comprising 2-pyrrolidone and N-alkyl-2-pyrrolidone is used, wherein the content ratio of 2-pyrrolidone to N-alkyl-2-pyrrolidone in the solvent system is from 90%:10% to 10%:90%, based on mass %, and wherein N-alkyl-2-pyrrolidone is N-propyl-2-pyrrolidone and/or N-butyl-2-pyrrolidone. Furthermore, the present invention relates to a porous membrane obtainable by said method. Moreover, the present invention relates to the use of a specific solvent system for the production of a porous membrane.
A device for mechanically stabilizing a sensor port on a flexible bag including a rigid, substantially plate-shaped support part, which has a receptacle for a rigid connecting part integrated in the bag, in particular a sensor, and a holding mechanism on the receptacle. The device further includes a fastening element adapted to be attached to the holding mechanism of the support part such that it fixes the support part to the connecting part. The device may include a rigid support part which can be assembled from at least two parts, preferably struts. The parts surround a free area or an opening in which a rigid connecting part integrated in the bag can be placed. In an assembled state of the parts, the free area or the opening has a smaller diameter than the connecting part, so that the parts form a load-receiving mechanism for the connecting part.
A small-volume liquid container for dispensing a liquid medium, especially biological medium, into a bioprocessing system, especially into a bioreactor, wherein the liquid container provides an accommodation volume for the liquid medium, wherein the liquid container comprises two dimensionally stable container parts, which are movable relative to one another between an initial position and an end position, and an outlet connection for discharge of the liquid medium. It is proposed that the liquid container comprises a shape-changeable delimitation means which at least sectionally delimits the accommodation volume and which is connected to the dimensionally stable container parts in such a way that a relative movement of the dimensionally stable container parts to one another, causing a change in volume of the accommodation volume, is associated with a change in shape of the delimitation means.
C12M 1/42 - Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic wave
90.
CROSSFLOW FILTRATION METHOD, METHOD FOR OBTAINING AT LEAST ONE CROSSFLOW FILTRATION PARAMETER AND SYSTEM FOR OBTAINING AT LEAST ONE CROSSFLOW FILTRATION PARAMETER
The present invention relates to a crossflow filtration method, a method for obtaining at least one crossflow filtration parameter and a system for obtaining at least one crossflow filtration parameter.
Various embodiments provide a connector for the sterile transfer of a liquid medium from a container to a bioprocess engineering system. The connector has two coupling devices. The coupling devices each have a housing and a control element which is adjustably mounted in the housing interior and forms a channel. The channel extends from a control element inlet opening to a control element outlet opening. The housings are able to be mechanically connected to one another and have a fluid inlet and a fluid outlet. The fluid outlet of one housing and the fluid inlet of the other housing overlap. The control elements are each adjustable from a starting position, into an operating position, in which the control element inlet opening is fluidically connected to the fluid inlet and the control element outlet opening is fluidically connected to the fluid outlet.
F16L 37/373 - Couplings of the quick-acting type with fluid cut-off means with fluid cut-off means in each of two pipe-end fittings with two taps or cocks
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
92.
CONTAINER FOR STORING, MIXING AND/OR CULTIVATING A MEDIUM
A container for storing, mixing and/or cultivating a medium, in particular a bioreactor for a medium, comprises a line system as a discharge line, feed line and/or bypass line of the bioreactor. The system can comprise a line body formed as a single piece for a medium to flow therethrough. The has a first and a second connection region for connecting in particular to the container and/or the line system and at least a first and a second coupling apparatus in the region between the connection regions.
A bioprocessing filtration experiment system for filtering a liquid test medium as part of a filtration experiment in a filtration experiment section of the filtration experiment system, which filtration experiment section runs from a receptacle for holding the test medium to be filtered to a fluid outlet for the filtered test medium, wherein the filtration experiment system is designed to ascertain, as part of the filtration experiment, sensor data as experiment data for at least one filter, said experiment data being able to be taken as a basis for selecting and/or dimensioning the filter of a target system according to predetermined scaling criteria. It is proposed that the filtration experiment system can be preassembled on an at least partially programming-related and/or circuit-related, at least partially fluidics-related and/or at least partially sensor-related basis.
A sensor positioning system for a bioprocess engineering unit, wherein a container is provided for receiving a biological medium which, when installed, extends in the axial direction from an upper container end to a lower container end, wherein a holder is provided for holding the container when installed, wherein a sensor is provided for fixing to the container. A positioning aid device for positioning the sensor to be fixed is provided on the container, the positioning aid device has a positioning aid that can be applied directly to or near the container on the holder, which can be brought into different vertical positions and/or circumferential positions relative to at least one reference point provided on the container and/or holder, and the positioning aid device has a technical storage medium or analog print medium with an allocation list.
C12M 1/06 - Apparatus for enzymology or microbiology with gas introduction means with agitator, e.g. impeller
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
G01F 23/00 - Indicating or measuring liquid level or level of fluent solid material, e.g. indicating in terms of volume or indicating by means of an alarm
A bioprocess device assembly includes at least a first bioreactor and a second bioreactor, and a transfer system for transferring a certain volume of a medium contained in the first bioreactor into the second bioreactor. A biomass sensor is associated to the first bioreactor. A control unit is configured for receiving measurement data from the biomass sensor and controlling the transfer system. An inoculation method makes use of such a device assembly wherein the biomass sensor measures at least one parameter of biomass contained in the first bioreactor; the biomass sensor sends measurement data to the control unit; and the control unit evaluates the measurement data and, based on an evaluation of the measurement data decides whether the viable cell density is sufficient for inoculation, determines a necessary inoculation volume, and controls the transfer system to transfer the determined inoculation volume from the first bioreactor into the second bioreactor.
A bioreactor for cultivating microorganisms and cells of animal or plant origin includes a filter pocket which is arranged on the inner surface of a flexible wall of the bioreactor and which is delimited on the outside by the wall of the bioreactor and on the inside by a filter pocket wall. The inside filter pocket wall is formed at least partially by a filter medium. A spacer is arranged in the filter pocket between the wall of the bioreactor and the filter medium. The spacer has at least one through opening. A connecting portion of the filter medium protrudes through the through opening and is directly connected to the wall of the bioreactor. A method of manufacturing a filter pocket in a bioreactor for cultivating microorganisms and cells of animal or plant origin is also provided herein.
Chromatography method, method of determining the influence of the interdependency of at least two parameters in a chromatography method and method of obtaining at least one chromatography method parameter
A chromatography method, a method of determining the concentration of at least one compound in a chromatography method and a method of obtaining at least one chromatography method parameter are provided. The methods can include selecting at least one compound, at least one stationary phase, at least one mobile phase, and at least one chromatography device having a chromatography bed comprising the at least one stationary phase and the at least one mobile phase.
A device for compensating short-term pressure or volume fluctuations of a medium in a continuously managed biopharmaceutical process including a receiving space in fluid communication with a process line through which a medium flows, an equalizing space, which is separated from the receiving space by a deflectable element, and a counter-pressure mechanism in the equalizing space for applying a counter-pressure to the deflectable element towards the receiving space. A method of compensating short-term pressure or volume fluctuations of a medium in a continuously managed biopharmaceutical process including providing a receiving space in fluid communication with a process line through which a medium flows, receiving an excess amount of the medium flowing into the receiving space, charging an energy storage device by the medium flowing into the receiving space, and expelling at least part of the excess amount if the pressure or flow rate falls below a set amount.
The present invention relates to a multimodal adsorption medium, in particular a multimodal chromatography medium, a method for its production, as well as use of the adsorption medium according to the invention or an adsorption medium produced according to the invention for the purification of biomolecules.
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
B01J 20/24 - Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
A mixing device having a stirring element can include: a container for receiving fluids and/or solids; and at least one rotatable stirring element for mixing the fluids and/or solids; wherein the stirring element comprises a first bearing element and a second bearing element which are arranged at or near opposite ends of the stirring element; wherein the first bearing element is mounted on a first face of the container and the second bearing element is mounted on an opposite second face of the container; wherein the first bearing element comprises at least one non-permanently magnetized element such that it can be moved in rotation by externally induced reluctance forces, and wherein the second bearing element is mounted in a contactless manner by externally induced magnetic forces.
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