Apparatus and method for producing a homogenised sterile liquid

Abstract

The invention relates to an apparatus (10) and a method for producing a homogenised sterile liquid. In order to provide an apparatus, in particular a compact apparatus, which integrates a plurality of process steps, the apparatus has the following basic features: a homogenisation device (30) having a homogenisation chamber (31); a base material supply device (14) connected to the homogenisation chamber (31); a sterile filter device (40) having a filtration chamber (41); a connecting line system (50) which fluidically connects the homogenisation device (30) and the sterile filter device (40) to one another; and a product discharge device (15) which is fluidically connected to the sterile filter device (40) via the connecting line system (50). Optionally, the apparatus (10) additionally comprises a water supply and cleaning device (20) which is fluidically connected to the homogenisation device (30) and / or the sterile filter device (40) via the connecting line system (50) and which in particular comprises a water supply unit (12) and / or a steam generation unit (25).

Description

[0001] Description

[0002] Device and method for producing a homogenized sterile liquid

[0003] The present invention relates to a device and a method provided for the production of a homogenized sterile liquid. In particular, the invention relates to a device and a method for the production of sterile liquid mixtures from solid forms.

[0004] Currently, there are two main methods for producing sterile liquid solutions from solids.

[0005] Industrial production is used by large manufacturers, such as producers of cell culture media. The homogenization and sterile filtration required for the production of the liquid are carried out using large-scale equipment and are suitable for production volumes from 50 to 100 liters, with standard volumes typically ranging between 1000 and 2000 liters.

[0006] For smaller batch sizes, the operational costs remain, resulting in significantly higher production costs.

[0007] The manufactured sterile products are packaged in plastic containers that are difficult to recycle. These products typically require low storage temperatures of 2 to 8 degrees Celsius and necessitate large storage and transport areas, negatively impacting the CO2 balance.

[0008] The production facilities are often inflexible and not suitable for manufacturing smaller batches.

[0009] End users have the option of either purchasing sterile, pre-filled liquid products or acquiring the base substances as ready-made mixtures or self-assembled components. In the latter case, homogenization and sterile filtration are performed by the end user. This decentralized solution requires considerable effort on the part of the end user and results in lower process reproducibility. The use of disposable sterile filters increases costs and has negative environmental impacts.

[0010] These existing methods therefore have significant disadvantages, particularly in terms of flexibility, production costs, environmental compatibility and process reproducibility.

[0011] The present invention therefore aims to provide a device, particularly a compact one, for the production of a homogenized sterile liquid that integrates several process steps. This is intended to create a sustainable, reproducible, and, in the long term, more cost-effective solution for the flexible in-house needs of end users.

[0012] This problem is solved according to the invention by the device with the features of independent claim 1, which represents the first aspect of the invention, by the method with the features of independent claim 16, which represents the second aspect of the invention, and by the particular use of independent claim 18, which represents the third aspect of the invention.

[0013] Further features and details of the invention will become apparent from the dependent claims, the description, and the drawings. Features and details disclosed in connection with one aspect of the invention also apply fully to all other aspects of the invention, and vice versa, so that the disclosure of each aspect of the invention always includes full reference to the other aspects. In particular, the sequence of the method according to the invention is also described in the functional description and the description of the interaction of the individual components of the device according to the invention. Therefore, to avoid repetition, the descriptions of the device according to the invention are also fully referenced with regard to the sequence and implementation of the methods according to the invention.

[0014] Before discussing the device and method according to the invention in detail, some basic explanatory remarks on the invention will first be made, which apply equally to both the device and the method.

[0015] The device according to the invention for producing a homogenized sterile liquid, which is also referred to synonymously as "the device" in the following, comprises a number of different components, which are described individually and in detail below. The device is provided in such a way that it is capable of producing such a liquid.

[0016] According to one embodiment, the individual components of the device are arranged in a housing. A housing is, in particular, a casing or enclosure that serves to protect the components of the device from external influences or to securely enclose them. This allows the device to be realized, in particular, as a compact, integrated unit that can also be used by end users. Such a housing-enclosed device is especially suitable for producing quantities of liquid suitable for end-use by individual end users.

[0017] According to one embodiment, the housing is in the form of a cuboid or cube. In another embodiment, the housing has a volume of less than or equal to 50 liters, preferably less than or equal to 20 liters. In another embodiment, the housing has a volume of less than or equal to 0.05 cubic meters. Compared to solutions known from the prior art for industrial production, the device according to the invention is preferably a small-scale plant. A "small-scale plant" is, in particular, a technical device that is used on a smaller scale compared to large industrial plants or complex technical systems.

[0018] Of course, designs are also possible in which individual components of the device are only functional parts of the device, without all of them having to be housed in a single casing.

[0019] According to one embodiment, the device has a modular design. This means that individual components are grouped and provided in the form of modules. A module is, in particular, an interchangeable, complex component within a complete system, in this case the device, which forms a closed functional unit. A device with such a modular design can therefore be assembled according to a building block principle and adapted as needed. The building block principle refers, in particular, to the ability to assemble various modules like building blocks to construct a multitude of different solutions, especially those adapted to external conditions and requirements. Due to the modular design, individual modules can be replaced, for example, if they are defective or if the device is to be used for a different application.It is also possible to adapt to changing circumstances, for example, to expand or reduce the capacity of the device, such as by changing the module size, a changing number of modules, and the like.

[0020] The homogenized sterile liquid is produced from a base substance. A base substance is, in particular, a substance from which other substances are produced through further processing. The base substance can be a solid, for example, in the form of a powder, a tablet, or the like. The base substance can also be a liquid that is enriched, as required, with further solid or liquid additives. According to one embodiment, the base substance is a mixture of several substances, such as salts, amino acids, sugars, and other small molecules.

[0021] The end product generated in the apparatus, hereinafter also referred to synonymously as "the product," is a sterile-filtered, homogenized liquid or solution that is, in particular, free of any germs. Such solutions are, in particular, components for other processes. For example, the products may be nutrient solutions, buffer solutions, or the like. The nature of the solution is determined, in particular, by its purpose and area of ​​application.

[0022] This will be illustrated using an example where the solution is a nutrient solution. A nutrient solution is a liquid containing many nutrients and is used especially for cultivating microorganisms, cells, or tissues. The nutrient solution is also called a culture medium. Nutrient solutions are, in particular, artificially produced solutions consisting of inorganic and / or organic substances. These substances are dissolved in water, such as distilled or deionized water. Such a nutrient solution is used, for example, in pharmaceutical and biotechnological applications. To maintain and grow cells in vitro, culture media with growth-promoting properties are needed. For example, to support the growth of many different mammalian cells, a culture medium used as a basal medium is required. One such basal medium is DMEM (Dulbecco's Modified Eagle Medium).In cell cultures, DMEM is used as a medium to promote the growth of various cell types.

[0023] The device and method according to the invention can be used to produce such nutrient solutions. That is to say, the device and the method are provided in such a way that they are capable of producing such a nutrient solution.

[0024] Naturally, the invention is not limited to the production of the liquids described above. Likewise, the invention is not limited to a specific field of application.

[0025] According to a preferred embodiment, the device and method according to the invention are used to produce a homogenized sterile liquid for application in biotechnology, pharmaceuticals, and food processing.

[0026] In the field of food processing, the present invention can be used, for example, in the production of novel foods. These include both newly developed and innovative foods as well as foods produced using new technologies and production methods. One such novel food, described here only for illustrative purposes and to be understood as a non-exclusive example, is so-called "cultured meat," also known as clean meat, in-vitro meat, or cell-based meat. Such cultured meat, the importance of which is steadily increasing, eliminates the need to breed, raise, and slaughter animals for food production.

[0027] The present invention relates in particular to a mobile and integrated device for homogenizing and producing sterile liquid mixtures from solid forms, including powders, tablets and other solids, especially for applications in biotechnology, pharmaceuticals and food processing.

[0028] The invention is realized in particular in the form of a compact, integrated device designed to gently and effectively mix solid base substances, such as chemicals, with water and then filter them under sterile conditions. The device according to the invention is easy to operate by the end user and can be operated under sterile conditions. Only deionized water, the base substances, and an electrical power supply are required for operation. The device is specifically designed to be used under a laminar flow hood or in other cleanroom conditions to meet the highest sterility requirements.

[0029] The device according to the invention has a number of advantages. It enables the production of a liquid in a single process run. The device integrates homogenization and sterile filtration, and optionally also cleaning of the device, in a compact system, which increases efficiency and ease of use. The device uses reusable filter elements and reduces the need for disposable materials, thus reducing environmental impact. This type of decentralized liquid production fundamentally enables a significantly more sustainable use of sterile liquids, such as cell culture media and buffers, compared to large-scale industrial production. The device reduces costs for end users because the considerably less expensive raw materials are used directly for decentralized production and use.Automation and integration of process steps ensure process reproducibility. The device is suitable for both small and large batches, allowing for flexible use. The ability to operate the device under sterile conditions and the provision of a cleaning option guarantee the highest sterility standards. Integrated sensors enable precise monitoring and control of the homogenization and filtration processes, further enhancing reproducibility.

[0030] According to the first aspect of the invention, a device for producing a homogenized sterile liquid is provided, which has the features of independent claim 1. A first component of the device is a homogenizing device. A homogenizing device is, in particular, a mixing device designed to break down solid and liquid particles into a uniform mixture. Typical applications of homogenizing devices include mixing and comminuting various materials such as particles, pigments, chemicals, plants, foodstuffs, cells, tissues, and the like. According to a preferred embodiment, mainly soluble solids are homogenized with water. This results in a liquid homogeneous mixture.Depending on the design, rotors, nozzles, or ultrasonic devices are used in the homogenizing devices to generate the forces required for comminuting and breaking up solids and liquid droplets. According to a preferred embodiment, the homogenizing device includes an ultrasonic device.

[0031] According to one embodiment, the homogenization device comprises a homogenization chamber in which the homogenization process is carried out. The homogenization chamber can be closed by a lid. The lid can have at least one passage for a base material supply device, which will be described in more detail later. According to one embodiment, the homogenization chamber and / or the lid is at least partially transparent, so that the progress of the homogenization, and possibly also the occurrence of problems, can be visually inspected.

[0032] According to one embodiment, the homogenizing device has various functions and elements, which will be explained in more detail later in this description. According to one embodiment, the homogenizing chamber has a coarse filter function for removing coarse impurities. According to one embodiment, the homogenizing device has a function for the continuous dissolution of the base substance. According to one embodiment, the homogenizing device has a function for circulating the liquid to be homogenized. This ensures continuous homogenization of the solution. According to one embodiment, the homogenizing device is equipped for real-time monitoring of the liquid to be homogenized. According to one embodiment, an ultrasonic device is associated with the homogenizing device, in particular with the homogenizing chamber. This supports rapid and efficient homogenization.According to one embodiment, the homogenizing device includes a sensor device in the form of a temperature sensor device. This monitors the temperature of the liquid to be homogenized during the homogenization process.

[0033] According to one embodiment, the homogenization device is designed to allow the liquid to be homogenized to circulate within it. A conventional stirred tank design is limited by its narrow, cylindrical geometry and the use of agitator blades. The homogenization device according to the present invention overcomes this limitation, allowing for more flexible integration of the homogenization process within a compact housing. This type of device is also gentler. This is particularly important when dissolving mixtures of multiple chemical substances to avoid or reduce unwanted reactions. These advantages are achieved primarily through the use of an ultrasonic device, which will be described in more detail later.

[0034] The homogenization chamber is connected to a base material supply unit. The base material is introduced into the homogenization chamber via this unit. The base material supply unit represents an interface of the device to the outside, through which the required base material is supplied to the device.

[0035] According to one embodiment, the homogenization device has at least one liquid supply device that provides access to the homogenization chamber. The liquid supply device can be, for example, the base substance supply device or a separate, independent supply device. The base substance and / or required additives can be introduced into the homogenization chamber via the liquid supply device, which also represents an external interface of the device. The liquid supply allows, for example, the manual addition of liquids to adjust parameters such as the pH value of the liquid to be homogenized. According to one embodiment, the liquid supply is provided for standard solutions to enable the regular calibration of measuring instruments.According to one embodiment, the base substance supply device and the liquid supply device are configured to hermetically seal the device from the outside during its intended use. "Hermetically" in this context means, in particular, that the seal is so tight that nothing can unintentionally enter or escape from the device.

[0036] For example, the feed device is designed in the form of an inlet channel, particularly a flexible one, that extends into the homogenization chamber. According to one embodiment, the feed device is externally closable, i.e., closed by a closing device. To prevent unwanted particles from entering the homogenization device when the feed device is opened, the closing device, according to one embodiment, includes an airlock, which may optionally contain a filter. If the device is arranged within a housing, one end of the feed device, which can be closed, for example, by the closing device, is located on or inside the housing wall.

[0037] A second component of the device is a sterile filter unit. During "sterile filtration," microorganisms are removed from the material being sterilized by filtration.

[0038] According to one embodiment, the sterile filter device has a filtration chamber in which the sterile filtration process is carried out. According to another embodiment, the filtration chamber has a lid. The filtration chamber and / or the lid is at least partially transparent, so that the progress of the filtration process, and possibly the occurrence of problems, such as a blockage of the filter, can be visually observed.

[0039] According to one embodiment, the sterile filter device has an automatic filtration function: The device has an automatic filtration function in which the homogenized liquid is pumped into the filtration chamber. Here, the liquid is passed through a sterile filter unit that removes microorganisms and other impurities. The device also has a connecting line unit through which the homogenizing device and the sterile filter unit are fluidically connected. The connecting line unit consists, in particular, of a number of line sections that are assembled together to form the connecting line unit. Individual line sections serve to connect individual components and elements of the device.Other pipe sections are provided in the form of bypass lines, which, for example, bypass the homogenizing device and the sterile filter unit. Other pipe sections can function as emergency drains from individual components. According to one embodiment, the circulation function in the homogenizing device is provided by the connecting pipe assembly, in particular by a number of pipe sections. Preferably, the connecting pipe, and especially the pipe sections, are made of stainless steel. Stainless steel is easy to clean, corrosion-resistant, and easy to disinfect, for example, by flame.

[0040] According to one embodiment, at least one pipe section, i.e., one or more pipe sections, is designed as a sterilization pipe section. In this context, the term "sterilization" is generally understood to also include cleaning itself, so that the sterilization pipe sections are synonymous with cleaning pipe sections. According to one embodiment, this means that these pipe sections are designed to transport a sterilizing agent / cleaning agent to a component to be sterilized / cleaned. Alternatively or additionally, a sterilization pipe section / cleaning pipe section can also be a pipe section that must be sterilized / cleaned, or is sterilized / cleaned, particularly at regular intervals.

[0041] According to one embodiment, the sterilizing agent / cleaning agent is steam. In this case, the at least one sterilization line section / cleaning line section is preferably designed or provided as a steam line section.

[0042] According to one embodiment, at least one sterilization line section / cleaning line section is provided for sterilizing / cleaning at least individual line sections of the connecting line assembly and / or for sterilizing / cleaning the sterile filter device. According to another embodiment, a water supply / cleaning device, described in more detail below, is fluidically connected to the sterile filter device via at least one sterilization line section / cleaning line section.

[0043] According to one embodiment, individual pipe sections of the connecting pipe assembly, for example those belonging to the homogenizing device and / or the sterile filtration device, are designed for continuous circulation, such that the homogenizing chamber and / or the filtration chamber can be traversed multiple times during the homogenization process and / or the cleaning process and / or the sterilization process until the desired result is achieved. This ensures continuous homogenization and / or sterile filtration. According to one embodiment, this circulation continues until the liquid is stable and meets all criteria.

[0044] The device further includes a product discharge unit, which is fluidly connected to the sterile filter unit via the connecting line. The finished homogenized sterile liquid is discharged from the device via the product discharge unit and can then be used for further processes. The product discharge unit thus represents an interface between the device and the outside. It is particularly important that the product discharge unit is designed to ensure that the generated liquid remains sterile. According to one embodiment, the product discharge unit is configured to hermetically seal the device to the outside during normal use.

[0045] For example, the product discharge device is designed in the form of a discharge channel, particularly a flexible one, that extends into a product container. According to one embodiment, the product discharge device is externally closable, i.e., sealed by a closing device. To prevent unwanted particles from entering the product discharge device when it is opened, the closing device, according to one embodiment, includes a gate, which may optionally contain a filter. If the device is arranged within a housing, one end of the product discharge device, which can be closed, for example, by the closing device, is located on or inside the housing wall.

[0046] According to one embodiment, the device has a water supply / cleaning device which is fluidly connected to the homogenizing device and / or the sterile filter device via the connecting line device.

[0047] The water supply / cleaning device can perform one or more functions. In one embodiment, the water supply / cleaning device serves only for water supply. In another embodiment, the water supply / cleaning device serves only for cleaning. In yet another preferred embodiment, the water supply / cleaning device serves for both water supply and cleaning. At least individual components of the device are cleaned, for example, the homogenizing device and / or the sterile filter device and / or the connecting line device. In one embodiment, the water supply / cleaning device is provided in such a way that it is capable of generating steam, which can then be used for sterilization.

[0048] For the purpose of water supply, the water supply / cleaning device, according to one embodiment, includes a water supply unit. This unit is designed, in particular, to hermetically seal the device to the outside during its intended use. The water supply unit, in turn, serves as an interface between the device and the outside. For example, the water supply unit is designed as an inlet channel, particularly a flexible one, that extends into a water container. According to one embodiment, the water supply unit is sealable to the outside, i.e., closed by a sealing device. To prevent unwanted particles from entering the device when the water supply unit is opened, the sealing device, according to one embodiment, includes a sluice gate, which may optionally contain a filter device.If the device is arranged within a housing, one end of the water supply unit, which can be closed, for example, by means of a sealing device, is located on or inside the housing wall. Water is particularly necessary when the base substance is provided in solid form. The water is then directed or pumped into the homogenization chamber, where it dissolves the base substance, which is present as a solid. The water supply unit is used, in particular, for supplying deionized water. According to one embodiment, the water supply / cleaning device is equipped with a water supply, in particular an automatic one, which offers two water supply points, for example, one for small bottles and one for larger containers. The water supply can be switched, for example, by means of a valve, in particular a manual one.

[0049] According to one embodiment, the water supply / cleaning device alternatively or additionally includes a steam generation unit. This unit serves for rinsing and disinfection using steam. The steam generation unit, which in particular provides a high-temperature steam cleaning function, allows at least individual components of the device, especially the homogenizing unit with the homogenizing chamber, and / or the sterile filter unit with the filtration chamber, and / or the filter devices, and / or the entire connecting pipe assembly, and / or individual pipe sections of the connecting pipe assembly, to be cleaned / sterilized, for example, disinfected, with high-temperature steam. The steam generation unit includes, in particular, mechanical and electronic safety devices for pressure protection.In one embodiment, a temperature sensor device is assigned to the steam generation device for measuring the steam temperature.

[0050] The steam generation device cleans / sterilizes and disinfects the individual components of the device. This can be further supported, if necessary, by the ultrasonic device described below.

[0051] The steam generation unit makes it possible, in particular, to perform a so-called CIP (Clean-in-Place) procedure. CIP means the cleaning of equipment on-site. The cleaning process is carried out without disassembly or significant changes to the operating state. CIP is therefore frequently used in hygiene-critical industries such as the food, beverage, and pharmaceutical industries. According to one embodiment, the device includes at least one ultrasonic device, which is specifically associated with the homogenization device and / or the sterile filter device. Ultrasonic homogenization, which is already known per se, is a mechanical process for breaking up and distributing particles in a liquid so that a uniform, homogeneous solution is created.The ultrasonic device supports rapid and efficient homogenization and / or sterile filtration and can additionally clean the filter devices, such as the homogenization unit and the sterile filter unit, during a cleaning procedure. According to one embodiment, homogenization is supported by an ultrasonic device to ensure rapid and efficient distribution of the solids.

[0052] According to one embodiment, the device has a backwash function that includes ultrasonic cleaning and cleaning / sterilization of the connecting line assembly.

[0053] According to one embodiment, the device has at least one pump assembly arranged in the connecting line assembly, or at least in one section of the connecting line assembly. The pump assembly serves to pump medium through the connecting line assembly. According to one embodiment, the water supply / cleaning device has one or two pump assemblies. One pump assembly serves to pump water to the homogenizing device. One pump assembly serves to pump water to the steam generating device. According to one embodiment, the homogenizing device has a pump assembly to pump the liquid to be homogenized through the homogenizing device, in particular to circulate it.

[0054] According to one embodiment, the device has at least one sensor device. Preferably, the device has two or more sensor devices. Depending on the intended application, the sensor devices can be configured differently. In particular, the at least one sensor device is selected from the group consisting of: pH sensor device, conductivity sensor device, temperature sensor device, pressure sensor device. Any combination thereof is also possible. Furthermore, the device, in particular the homogenization device, can have one or more, for example, two air filters / pressure equalization devices.

[0055] pH and conductivity sensors are used for real-time monitoring of the liquid during the homogenization process. According to one embodiment, such sensor devices are integrated into the homogenization apparatus.

[0056] Temperature sensors monitor the liquid temperature during the homogenization process and / or the sterile filtration process. These temperature sensor devices provide a real-time display of the liquid temperature in the chambers. Temperature sensor devices also monitor the temperature in the steam generation unit. According to one embodiment, a temperature sensor device is assigned to the homogenization unit, the sterile filtration unit, and / or the steam generation unit.

[0057] According to one embodiment, a pressure sensor is provided upstream of or within the sterile filter device. The pressure readings indicate whether the sterile filter device, and in particular the filter assembly, is functioning correctly. An unusual pressure increase, for example, could indicate that the filter assembly is clogged. The pressure sensor can also be used to monitor the steam during cleaning / disinfection. The pressure typically increases with increasing flow rate, thus forming a characteristic pattern. This pattern is used, for example, for integrity testing to verify the filter's functionality before filtration. If the filter were not airtight, i.e., not intact, a normal pressure profile could not be established. Such leaks could allow germs to enter the product.However, if the pressure is above the normal ratio, it would be considered a sign of a blocked filter.

[0058] According to one embodiment, the device has at least one filter device. The filter device is selected, in particular, from the group consisting of: a coarse filter device, a sterile filter device. Any combination thereof may also be provided. According to one embodiment, a filter device is associated with the homogenizing device. This filter device may, for example, be located within the homogenizing chamber. According to one embodiment, this filter device removes coarse impurities. The filter device is, for example, designed as a coarse filter, such as a 10 pM filter.

[0059] According to one embodiment, a filter unit is associated with the sterile filtration system. The homogenized solution is passed through the sterile filter, which removes microorganisms and other impurities. The filter unit can be designed in different ways. According to one embodiment, the filter unit is designed as a depth filter. Depth filters consist, for example, of a fibrous network of overlapping paper, asbestos, or borosilicate glass fibers. The particles passing through are thus retained inside the fibers. According to another embodiment, the filter unit is designed as a membrane filter. Membrane filters consist, for example, of polymers. Their effect can be compared to a sieve. They allow a high flow rate and can also be used for small and large volumes of liquid. The filter unit is, for example, a 0.22 ppm sterile filtration system.

[0060] According to one embodiment, the filter devices are made of stainless steel. This makes it possible to clean / sterilize them multiple times with a sterilizing agent / cleaning agent, for example with steam, for example to disinfect them.

[0061] According to one embodiment, the device has at least one valve assembly which is arranged or formed in the connecting line assembly, for example in at least one section of the connecting line assembly. The valve assembly is selected in particular from the group consisting of: shut-off valve assembly, changeover valve assembly, multi-way valve assembly. Any combination thereof is also possible.

[0062] If the water supply / cleaning device has a water supply function with two water supply points, these can be switched by a valve device, particularly a manual one. Multi-way valve devices can be located between the water supply / cleaning device and the homogenizing device, and / or between the homogenizing device and the sterile filter device, and / or between the sterile filter device and the product discharge device. According to one embodiment, the device for producing a homogenized sterile liquid has a homogenizing device and a sterile filter device, each of which is associated with an ultrasonic device. The device also has a water supply / cleaning device. An exemplary embodiment of the basic operation of such a device is as follows:

[0063] The device is filled with deionized water and the required base substances. For example, a flexible inlet channel is immersed in a water vessel. Water is pumped by an integrated pump into the homogenization chamber, where the base substance(s) is / are added. Homogenization is achieved through a continuous circuit through the filter unit, assisted by the ultrasonic device. pH and / or conductivity sensors monitor the solution in real time. After homogenization, the solution is passed through the sterile filter to obtain a sterile liquid. The sterile solution is pumped out of the product discharge unit through the disinfected outlet channel. The steam generation unit produces steam from the water vessel and cleans the filters and the system, in particular the sterile filter unit and / or at least individual sections of the connecting line unit.The pressure sensor monitors the cleaning process.

[0064] According to one embodiment, the device has a control unit for operating and controlling the processes, which is designed to control at least individual components of the device.

[0065] The control unit is, in particular, the entirety of all elements that influence the device. The control unit can be designed in the form of hardware components or software components, or as a combination thereof. In particular, the control unit comprises a computer system in which at least parts of the method according to the second aspect of the invention take place, or in which a computer program is implemented.

[0066] According to one embodiment, the control unit also includes a storage device for storing data, and / or an input device for inputting information and commands, and / or a display device for showing information, in particular a display. The control unit is connected to the components of the device to be controlled via suitable signal connections. Depending on the design, the control unit is at least partially an integral part of the device. Alternatively, the control unit is an external component that is then at least temporarily connected to and communicates with the device via interfaces and signal connections.

[0067] In connection with the device, the control unit may in particular also have the following features and perform the following functions:

[0068] The control unit can have a unified control panel that operates all functions with a single button press. The control unit provides real-time monitoring of the liquid within the device. It can automatically monitor several parameters, such as the pH value and conductivity of the liquid. The control unit thus provides a monitoring function for the pH value and conductivity of the liquid. It also enables a real-time display of the liquid temperature in the chambers and monitoring of the steam cleaning temperature. The homogenizing device and / or the sterile filter device have a temperature monitoring function via the control unit for real-time display of the liquid temperature.

[0069] According to the second aspect of the invention, a method for producing a homogenized sterile liquid is provided, which has the features of independent claim 16. That is, the method is provided in such a way that it is capable of producing or manufacturing such a liquid. The method is carried out, in particular, using a device according to the first aspect of the invention. For this reason, to avoid repetition, full reference is made here to the explanations of the first aspect of the invention, as well as to the general description of the invention above. The method is characterized by the following steps:

[0070] A base substance is fed to a homogenization device via a base substance feed unit and homogenized in the homogenization device to form a homogenized liquid. If necessary, the homogenization device is circulated multiple times until the desired result is achieved. This ensures continuous homogenization and / or sterile filtration. According to one embodiment, this circulation continues until the liquid is stable and meets all criteria.

[0071] The homogenized liquid is then fed to a sterile filter device via a connecting line device, in particular via at least individual line sections of the connecting line device, and is sterile-filtered in the sterile filter device to produce a sterile-filtered liquid.

[0072] The sterile-filtered liquid is then fed via the connecting line device, in particular via individual line sections of the connecting line device, to a product discharge device and discharged from the device via this device.

[0073] According to one embodiment, a water supply / cleaning device is installed upstream of the homogenizing device and the sterile filter device. This device provides water which is pumped into the homogenizing chamber of the homogenizing device for the purpose of homogenizing the base substance.

[0074] For cleaning and sterilization purposes, water is fed into a steam generation device via the water supply / cleaning unit. There, steam is generated, which is then passed, in particular pumped, through the connecting pipework, for example, individual pipe sections and / or the homogenizing device and / or the sterile filter device, thereby cleaning / sterilizing, for example, disinfecting these components.

[0075] According to one embodiment, at least individual components of the device, in particular individual sections of the connecting line assembly and / or the sterile filter assembly, are cleaned / sterilized at least at regular intervals. To avoid repetition, reference is made in full to the explanations relating to the first aspect of the invention and to the general description of the invention above.

[0076] According to one embodiment, the present invention relates in particular to an integrated system for producing sterile liquid mixtures from solids, specifically designed for flexible, in-house applications. The compact device integrates several process steps and is characterized by efficiency, sustainability, and ease of use. The device comprises a flexible stainless steel inlet channel that can be immersed in a water vessel and an integrated pump unit that delivers water into a homogenization chamber. In this chamber, the solids are homogenized by circulation and ultrasound and filtered through a 10 pM filter. pH and conductivity sensors monitor the solution in real time to ensure precise control and reproducibility. After homogenization, the solution is pumped through a 0.22 pM sterile filter and discharged into a sterile outlet channel.The system also features a cleaning unit, such as a CIP (Clean-in-Place) system, which enables effective disinfection and cleaning of the entire system using steam. An integrated ultrasonic device further supports homogenization and filter cleaning. All processes are controlled via an integrated control panel, allowing for simple and intuitive operation. The device offers a sustainable alternative to conventional methods by reducing the use of single-use plastic containers and minimizing the need for large storage areas. Its versatile functionality makes it a cost-effective and environmentally friendly solution for end users who require flexible and reproducible production of sterile solutions.

[0077] The invention will now be explained in more detail with reference to exemplary embodiments and the accompanying drawings. These show...

[0078] Figure 1 shows a schematic view of the device for producing a homogenized sterile liquid according to a first embodiment of the present invention;

[0079] Figure 2 shows the device depicted in Figure 1, wherein the modular nature of the

[0080] The device is shown;

[0081] Figure 3 shows the device depicted in Figure 1, with the addition that

[0082] The control unit and its signal connection to the individual components of the device are shown;

[0083] Figure 4 shows the device depicted in Figure 1, with reference to which the process of the inventive method is described; Figures 5 and 6 show a further embodiment of a device for producing a homogenized sterile liquid according to the present invention; and

[0084] Figure 7 shows the process flow in the environment depicted in Figures 5 and 6

[0085] Example of implementation.

[0086] Figures 1 to 4 show a device 10 for producing a homogenized sterile liquid, which is hereinafter referred to as device 10. The device 10 is used to produce a homogenized sterile liquid for applications in biotechnology, pharmaceuticals, or food processing.

[0087] The device 10 comprises a number of components, all of which are arranged within a housing 11. This enables a compact design of the device 10. A water supply device 12, a further water supply device 13 (which may also function as a water outlet device), a base substance supply device 14, and a product discharge device 15 are located in or on the wall of the housing.

[0088] The device 10 comprises a water supply / cleaning device 20, a homogenizing device 30, and a sterile filter device 40, which are fluidly interconnected via a stainless steel connecting line assembly 50. The connecting line assembly 10 consists of a number of line sections 50a to 50q, with a further line section 50r designed as a bypass line.

[0089] The water supply / cleaning device 20 can serve as a water supply for the homogenizing device 30. For this purpose, the water supply device 12 is connected via a pipe section 50a to a valve assembly 21 designed as a diverter valve. The valve assembly 21 is also connected to the water supply device 13 via a pipe section 50b. Depending on the position of the valve assembly 21, switching between the water supply device 12 and the water supply device 13 is possible. In this implementation, the water supply devices 12 and 13, or the pipe sections 50a and 50b, can be combined in a single component. The connecting pipe assembly branches into a pipe section 50c and a pipe section 50d via a branching device 27 in the form of a T-piece.In order to supply water to the homogenizing device 30, a pumping device 22 is activated in the connecting line device 50, which pumps the water, in particular deionized water, via the line section 50a and a valve device 24 in the form of a multi-way valve into the homogenizing device 30, in particular into a homogenizing chamber 31.

[0090] The water / cleaning device 20 can also perform a cleaning and disinfection function. This is done using hot steam. For this purpose, a further pump unit 23 in the connecting line unit 50 is activated, which transports the water via line section 50d to a steam generator 25. The temperature of the generated steam is measured by a sensor unit 26 in the form of a temperature sensor. The steam is transported via line section 50e to the valve unit 24, and from there on to the homogenizing device 30 and / or the sterile filter unit 40 and / or the corresponding line sections of the connecting line unit 50. These components can then be cleaned and disinfected using the steam.

[0091] Water is required to produce a homogenized liquid in the homogenizing device 30. The homogenizing device 30 has a homogenizing chamber 31, which is connected via a pipe section 50f to the valve assembly 24 and thus to the water supply device 12 or 13. A filter assembly 32 in the form of a coarse filter is located in the homogenizing chamber 31. A sensor assembly 39 in the form of a temperature sensor is also arranged in the homogenizing chamber 31. A lid assembly 33 closes the homogenizing chamber 31 at the top. If the homogenizing chamber 31 and / or the lid assembly 33 are at least partially, preferably completely, transparent, this allows a view into the homogenizing chamber 31.

[0092] In addition to water, the base substance is fed into the homogenization chamber 31 via the base substance feed device 14. Homogenization is carried out using an ultrasonic device 34. Sensor elements 35a, 35b, in the form of a pH sensor element and a conductivity sensor element, measure these values ​​in the liquid to be homogenized, preferably continuously. Any necessary pressure equalization can be achieved via air filters / pressure equalization devices 36a, 36b. The liquid to be homogenized is circulated through the line sections 50g, 50h, 50i, particularly with the aid of a pump device 37, until the sensor readings 35a, 35b indicate the required values. This then confirms that the liquid has been fully homogenized. The homogenized liquid then passes into the sterile filter device 40 via a valve device 38 in the form of a multi-way valve device.For safety purposes, a pipe section 50q running from the homogenization chamber 31 towards the valve assembly 24 is provided as an emergency drain. Likewise, an emergency drain assembly 16 is connected to the valve assembly 38 via a pipe section 50n.

[0093] After passing through the homogenization device 30, the homogenized liquid flows via the valve assembly 38 and a line section 50j into the filtration chamber 41 of the sterile filter device 40. A filter assembly 42, part of a sterile filter, is located in the filtration chamber 41. A lid assembly 43 closes the filtration chamber 41 at the top. The filtration chamber 41 and / or lid assembly 43, which are at least partially, preferably completely, transparent, allow visual inspection into the filtration chamber 41. An ultrasonic device 44 is also associated with the sterile filter device 40. The sterile-filtered liquid exits the filtration chamber 41 via the line section 50k towards a valve assembly 45, which is designed as a multi-way valve. The line sections from 50k onwards must be operated strictly in one direction to ensure sterility.During cleaning, liquid may also be circulated alongside steam. If necessary, this can be done via pipe sections 50I, 50m, 50j, and 50k. Backwashing can also be performed using pump 37.

[0094] The finished homogenized sterile liquid leaves the device 10 via the valve assembly 45 and a line section 50p towards the product discharge device 15. A sensor device 46 in the form of a pressure sensor element is provided for pressure measurement, which provides information about the functionality of the filter assembly 42 and is also used for pressure measurement during a cleaning process. The liquid, or water, can be bypassed around the homogenization chamber 31 and the filtration chamber 41 via the bypass line 50r if necessary. Figure 2 shows the embodiment according to Figure 1, wherein the water supply / cleaning device 20 is designed as a water supply / cleaning module 20a, the homogenization device 30 as a homogenization module 30a, and the sterile filter device 40 as a sterile filter module 40a.The transitions between the individual modules are formed by the valve assemblies 24 and 38, which either belong to one of the modules or are provided as independent components between the modules. This simplifies the replacement of individual modules, if desired or necessary.

[0095] According to one embodiment, the device 10 can be described as follows. The device 10 enables the single production of a finished solution in a single process run. An inlet channel made of stainless steel, serving as a water supply device 12, is immersed in a container 70 containing deionized water (see Figure 4). The device 10 is equipped with an automatic water supply system that provides two water supply devices 12, 13, for example, one for small bottles and one for large containers. The water withdrawal can be switched using the manual valve device 21. The homogenization chamber 31 has several functions. A filter device 32 in the form of a coarse filter removes coarse impurities. The possibility of circulation ensures continuous homogenization of the liquid. Real-time monitoring of the liquid is possible via sensor elements.The ultrasonic device 34 supports rapid and efficient homogenization. A temperature sensor device 39 monitors the liquid temperature during the homogenization process. The device 10 features an automatic filtration function, in which the mixed, i.e., homogenized, liquid is pumped into a filtration chamber. Here, the liquid passes through a sterile filter device 42, which removes microorganisms and other impurities. The finished solution is discharged via the outlet channel in the form of the product discharge device 15.

[0096] Device 10 has a backwash function that includes ultrasonic cleaning and connecting line cleaning. The device can disinfect the homogenization chamber 31, the filtration chamber 41, and the entire connecting line assembly 50 with high-temperature steam. The base material feed unit 14, or an independent additional feed unit, allows the manual addition of liquids to adjust parameters such as the pH value of the liquid. Device 10 can automatically monitor several parameters, such as pH value and conductivity, of the liquid via the sensor units 35a and 35b. Real-time display of the liquid temperature in chambers 31 and 41, as well as monitoring of the steam cleaning temperature, is possible via temperature sensor units. The steam generation unit 25 has mechanical and electronic safety devices for pressure protection.The steam generating unit 25 cleans and disinfects the filter units 32, 42. The ultrasonic unit 43 supports homogenization and cleans the filter unit 32 during the cleaning process.

[0097] A control unit 60 controls the individual components of the device 10. This is illustrated in Figure 3. Figure 3 shows the device 10 according to Figure 1, so that for the description of its structure, reference is initially made to the description of Figure 1. Additionally, Figure 3 shows the control unit 60 of the device 10. This unit comprises a computer unit 61, a storage unit 62 for storing data, a display unit 63, and an input unit 64. The individual components of the device 10 are connected to the control unit 60 via corresponding signal connections 65a to 65w.

[0098] The process for producing a homogenized sterile liquid is now explained with reference to Figure 4. The device shown in Figure 4 corresponds in structure to the device 10 from Figure 1. It is also shown that, on the inlet side, the device 10 is connected via the water supply device 12 to an inlet channel 71, which leads into a water container 70. On the outlet side, the device 10 is connected via the product discharge device 15 to an outlet channel 73, through which the homogenized sterile liquid is collected in a product container 72. In the device 10, the product homogenized sterile liquid is produced from the starting product water, which is supplied to the device 10 via the water supply device, and the starting product base substance, which is supplied to the device 10 via the base substance supply device 14. This product is then discharged from the device 10 via the product discharge device 15.

[0099] The process sequence is as follows: The device is filled with deionized water and the required base substances. The inlet channel 71, which is particularly flexible, is immersed in the water reservoir 70. Water is pumped by the integrated pump unit 22 into the homogenization chamber 31, where the base substances are added. Homogenization is carried out by a continuous circuit through the filter unit 32, for example, a 10 pM filter, supported by the ultrasonic device 34. The pH and conductivity sensors 35a and 35b monitor the liquid in real time. After homogenization, the liquid is passed through the filter unit 42, for example, through a 0.22 pM sterile filter, or the sterile filter unit 40 to obtain a sterile liquid. The homogenized sterile liquid is pumped out through the disinfected outlet channel in the form of the product discharge unit 15 and the outlet channel 73.The steam generating unit 25 produces steam from the water tank 70 and cleans the filter units 32, 42 and the connecting line unit 50. The pressure sensor 46 monitors the cleaning process.

[0100] Figures 5 to 7 show a further embodiment of the device 10 according to the invention, with figure 7 showing the process flow in this embodiment.

[0101] The basic components and features of the embodiment shown in Figures 1 to 4 are also implemented in the embodiment shown in Figures 5 to 7. These components are only arranged differently in this second embodiment. Therefore, identical components are provided with identical reference numerals, so reference is made to the descriptions of Figures 1 to 4. The liquid produced in the device 10 is discharged from the device 10 via the product discharge device 15 and collected in a container 72, for example, a sealable bottle.

[0102] Figure 7 also illustrates the process flow. In particular, the direction of movement or flow during individual process steps is shown by corresponding arrows. WD stands for steam, L for air, W for water, and F for filtration. The corresponding marked arrows indicate the direction of movement or flow of the individual media through the device, or the direction of filtration. The steam WD serves to clean / sterilize the respective pipe sections through which it flows and / or to transport it to individual components that are to be cleaned / sterilized, for example, the sterile filter device 40. An example for the production of a sterile PBS solution (phosphate-buffered saline) is described below. In this example, the device 10 is used to produce 1 liter of a sterile PBS solution.The base substance is PBS powder, used in an amount equivalent to 1 liter of finished solution.

[0103] Preparation: o Prepare the required amount of PBS powder needed for 1 liter of PBS solution. o Fill the water reservoir with deionized water.

[0104] First run: The flexible inlet channel 71 is immersed in the water reservoir 70 and the device 10 is switched on. 500 ml of water are pumped into the homogenization chamber 31. The PBS powder is added to the homogenization chamber 31. Homogenization begins, optionally assisted by the ultrasonic device 34 to ensure uniform distribution of the powder. The liquid is circulated through the filtration device 32, consisting of a 10 pM filter, while the pH and conductivity sensors 36 and 37 monitor the liquid. After homogenization is complete, the liquid is passed through the filtration device 42, consisting of the 0.22 pM sterile filter of the sterile filtration device 40, to obtain a sterile, highly concentrated PBS solution.

[0105] Second pass: o In this pass, only deionized water is filtered. o 500 ml of water are pumped again through the 0.22 pM sterile filter and added directly to the double-concentrated PBS solution. o The result is 1 liter of sterile PBS solution.

[0106] Alternative method: o The user can also choose to prepare two 500 ml x1 PBS solutions, depending on individual needs. o In this case, the homogenization process is carried out twice, each time with 500 ml of water and the corresponding amount of PBS powder. o After each pass, the solution is passed through the 0.22 M sterile filter to obtain two separate 500 ml x1 PBS solutions. Once the production of the PBS solution is complete and no further production is scheduled for the same day, the cleaning process, for example, the CIP (Clean in Place) program, can be started. The CIP module, in the form of the steam generation unit 25, generates steam from the water tank 70 and cleans and disinfects the filter units 32 and 42 and the connecting line unit 50. The pressure sensor 46 monitors the CIP process to ensure that the cleaning is carried out effectively. After completion of the CIP program, the unit 10 is switched off.

[0107] This example demonstrates how the device 10 can be used to flexibly and efficiently produce sterile solutions while ensuring ease of use and cleaning. The user can prepare different quantities and concentrations of the solution as needed, highlighting the versatility and adaptability of the device 10.

[0108] In summary, the present invention relates to a device 10 and a method for producing a homogenized sterile liquid. To provide a particularly compact device that integrates several process steps, the device has the following basic features: a homogenization device 30 with a homogenization chamber 31; a base substance feed device 14 connected to the homogenization chamber 31; a sterile filter device 40 with a filtration chamber 41; a connecting line device 50 through which the homogenization device 30 and the sterile filter device 40 are fluidly connected; and a product discharge device 15, which is fluidly connected to the sterile filter device 40 via the connecting line device 50.Optionally, the device 10 additionally has a water supply / cleaning device 20, which is fluidly connected to the homogenizing device 30 and / or the sterile filter device 40 via the connecting line device 50, at least via individual line sections of the connecting line device 50, and which in particular has a water supply device 12 and / or a steam generation device 25.

[0109] Reference symbol list

[0110] 10 Device for producing a homogenized sterile liquid

[0111] 11 cases

[0112] 12 Water supply system

[0113] 13 Water supply system

[0114] 14 Basic substance delivery device

[0115] 15 Product removal device

[0116] 16 Emergency exit device

[0117] 20 Water supply / cleaning device

[0118] 20a Water supply / cleaning module

[0119] 21 Valve assembly

[0120] 22 Pump system

[0121] 23 Pump system

[0122] 24 Valve assembly

[0123] 25 Steam generating plant

[0124] 26 Sensor device (temperature)

[0125] 27 Branching device (T-piece)

[0126] 30 Homogenizing device

[0127] 30a Homogenization module

[0128] 31 Homogenization chamber

[0129] 32 Filter unit (coarse filter)

[0130] 33 Lid mechanism

[0131] 34 Ultrasound device

[0132] 35a Sensor device (pH value)

[0133] 35b Sensor device (conductivity)

[0134] 36a Air filter / pressure equalization device

[0135] 36b Air filter / pressure equalization device 37 Pump device

[0136] 38 Valve assembly

[0137] 39 Sensor device (temperature)

[0138] 40 Sterile filter device

[0139] 40a Sterile filter module

[0140] 41 Filtration chamber

[0141] 42 Filter unit (sterile filter)

[0142] 43 Lid mechanism

[0143] 44 Ultrasound device

[0144] 45 Valve assembly

[0145] 46 Sensor device (pressure)

[0146] 50 Connecting line device

[0147] 50a to 50q line section

[0148] 50r pipe section (bypass)

[0149] 60 Control unit

[0150] 61 Computer setup

[0151] 62 Storage device

[0152] 63 Display unit (display)

[0153] 64 Input device

[0154] 65a to 65w signal connection

[0155] 70 water containers

[0156] 71 Input channel

[0157] 72 product containers

[0158] 73 Output channel

[0159] Water

[0160] L air

[0161] F Filtration

[0162] WD Water vapor

Claims

Patent claims 1. Device (10) provided for the production of a homogenized sterile liquid, comprising a homogenizing device (30) with a homogenizing chamber (31), a base substance supply device (14) connected to the homogenizing chamber (31), a sterile filter device (40) with a filtration chamber (41), a connecting line device (50) via which the homogenizing device (30) and the sterile filter device (40) are fluidly connected to each other, and a product discharge device (15) which is fluidly connected to the sterile filter device (40) via the connecting line device (50).

2. Device according to claim 1, characterized in that the device (10) has a water supply / cleaning device (20) which is fluidly connected to the homogenizing device (30) and / or to the sterile filter device (40) via the connecting line device (50).

3. Device according to claim 2, characterized in that the water supply / cleaning device (20) comprises a water supply device (12) and / or a steam generation device (25).

4. Device according to one of claims 1 to 3, characterized in that the connecting line device (50) has a number of line sections (50a to 50r, WD).

5. Device according to claim 4, characterized in that one or more conduit sections are designed as sterilization conduit section(s), in particular as steam conduit section(s) (WD).

6. Device according to claim 5, characterized in that at least one sterilization line section is provided for the sterilization of at least individual line sections of the connecting line device (50) and / or for the sterilization of the sterile filter device (40).

7. Device according to claim 5 or 6, insofar as it relates back to claim 2 or 3, characterized in that the water supply / cleaning device (20) is fluidly connected to the sterile filter device (40) via at least one sterilization line section.

8. Device according to one of claims 1 to 7, characterized in that the device (10) has at least one ultrasound device (34, 44) which is associated with the homogenizing device (30) and / or the sterile filter device (40).

9. Device according to one of claims 1 to 8, characterized in that the device (10) has at least one pump device (22, 23, 37) which is arranged in at least one of the line sections of the connecting line device (50).

10. Device according to one of claims 1 to 9, characterized in that the device (10) has at least one sensor device (26, 35, 39, 46), and that the sensor device (26, 35, 39, 46) is in particular selected from the group consisting of: pH value sensor device, temperature sensor device, pressure sensor device, or a combination thereof.

11. Device according to one of claims 1 to 10, characterized in that the device (10) has at least one filter device (32, 42), and that the filter device (42) is in particular selected from the group consisting of: coarse filter device, sterile filter device, or a combination thereof.

12. Device according to claim 11, characterized in that the filter device (32, 42) is associated with the homogenizing device (30) and / or the sterile filter device (40).

13. Device according to one of claims 1 to 2, characterized in that the device (10) has at least one valve assembly (21 , 24, 38, 45) which is arranged or formed in the connecting line assembly (50), and that the valve assembly (21 , 24, 38, 45) is in particular selected from the group consisting of: shut-off valve assembly, changeover valve assembly, multi-way valve assembly, or a combination thereof.

14. Device according to one of claims 1 to 13, characterized in that the device (10) has a control unit (60) which is configured to control at least individual components of the device (10).

15. Device according to one of claims 1 to 14, characterized in that the individual components of the device (10) are arranged in a housing (11), and / or that the device (10) is designed modularly (20a, 30a, 40a).

16. Method for producing a homogenized sterile liquid, in particular using a device (10) according to any one of claims 1 to 15, characterized by the following steps: A base substance is supplied to a homogenization device (30) via a base substance supply device (14) and homogenized in the homogenization device (30) to form a homogenized liquid, the base substance being circulated in particular in the homogenization device (30); The homogenized liquid is then fed to a sterile filter device (40) via a connecting line device (50) and sterile-filtered in the sterile filter device (40) to produce a sterile-filtered liquid; The sterile-filtered liquid is then fed via the connecting line device (50) to a product discharge device (15) and discharged from the device (10) via this device.

17. Method according to claim 16, characterized in that at least individual components of the device (10), in particular individual sections of the connecting line device (50) and / or the sterile filter device (40), are cleaned or sterilized at least at intervals.

18. Use of a device (10) according to any one of claims 1 to 15 or of a method according to claim 16 or 17 for producing a homogenized sterile liquid for an application in biotechnology, pharmaceuticals, or food processing.

Images