Method of operating a bioprocess arrangement to perform at least one repetition of a bioprocess

Abstract

The present invention relates to a method for operating a biological process arrangement (1) to perform at least one repetition of a biological process, wherein the biological process arrangement (1) includes at least one replaceable electronic component (8), and wherein a process control system (7) controls the biological process arrangement (1) using a digital model (10). The method proposes that a replaceable electronic component (8) is removed and replaced by a new electronic component (9), the process control system (7) automatically detects the removal of the replaceable electronic component (8), automatically detects the presence of the new electronic component (9), and retrieves the digital representation (11) of the new electronic component (9) based on communication with the new electronic component (9). The process control system (7) derives a functional relationship between the replaceable electronic component (8) and the new electronic component (9) from the digital representation (11) of the replaceable electronic component (8) and the new electronic component (9). Based on the functional relationship, the process control system (7) replaces the digital representation (11) of the replaceable electronic component (8) with the digital representation (11) of the new electronic component (9), thereby updating the digital model (10), and the process control system (7) controls the biological process arrangement (1) to perform the biological process based on the updated digital model (10).

Description

Technical Field

[0001] The present invention relates to a method for operating a biological process arrangement to perform at least one repetition of a biological process according to the general part of claim 1, an electronic component according to claim 17, and a process control system according to claim 18. Background Technology

[0002] The term "bioprocess" now refers to any kind of biotechnological process, particularly biopharmaceutical processes. An example of such a bioprocess is the use of a bioreactor to culture microorganisms or mammalian cells under given conditions.

[0003] The number of sensors and actuators connected to bioprocess equipment has increased significantly due to several factors, including regulatory pressures, cost pressures, process intensification, and flexibility requirements. This has created a “zoo” of connectors and signal types for digital, analog, and networked devices on the market.

[0004] Although many plug-and-play concepts have been proposed, plug-and-play components using standardized interfaces are not yet widely available. Instead, different bus systems are used today.

[0005] As new sensors are developed and marketed, equipment must be upgraded with new hardware and software. This is not only a burden for product development but also a problem for customers, as field upgrades are not always possible, and equipment revalidation is expensive and time-consuming. In the future, smart sensors can provide all the information a device needs without intervention from automation engineers and without triggering revalidation, thereby reducing costs and increasing the capabilities and flexibility of the equipment.

[0006] The prior art upon which this invention is based (EP 3839670 A1) relates to a method according to the general part of claim 1. This prior art generally teaches the use of plug-and-play components, reading functional information from these components, and configuring biological processes based on that functional information. Typically, process control systems in biotechnology use digital models with digital representations of (replaceable) physical components for controlling the process (i.e., the physical components) and for communicating with the user.

[0007] At a more general level, standards such as IEEE 1451 define possible communication methods between components. Furthermore, standards like Modbus are commonly implemented and used in process control systems. However, IEEE 1451 is not widely applicable in the biotechnology field, and some implementations can be overly complex, especially for inexpensive, disposable components. Modbus is simple to implement but places a burden on the operator.

[0008] Improving plug-and-play capabilities in biotechnology is a challenge. Summary of the Invention

[0009] This invention addresses the problem of improving known methods by making it easier to integrate plug-and-play components into workflows. Another objective is to propose components that are specifically well-usable in the proposed methods, serving as plug-and-play components.

[0010] The features of the feature portion of claim 1 achieve the above-mentioned objective.

[0011] The main implementation of this invention is that the production of bioproducts leads to frequent replacements of electronic components, particularly disposable ones. Electronic components need to be replaced between batch production runs or sometimes during continuous processes. Replacement components can be substantially the same. However, it is also possible that upgraded components are available and should be used. Due to these changes, the digital representation of the physical components and the process control flowcharts (a type of digital model) based on these digital representations are “out of sync” with the real world and need to be reconfigured. Typically, automatically reconfiguring the digital model is challenging because it may not be clear how newly detected components should be used. However, in the field of biotechnology, component changes are a frequent and repetitive process. Therefore, it is easier to detect new components and find their functional relationship with previously removed components to identify the new component as a replacement. The digital model can then be reconfigured automatically or a reconfiguration can be suggested to the user (preferably in a manner where the user only needs to confirm correct detection).

[0012] In detail, a method is proposed where replaceable electronic components are removed during and / or between repetitions of a biological process and replaced with new electronic components. The process control system automatically detects the removal of replaceable electronic components, automatically detects the presence of new electronic components, communicates with the new electronic components, retrieves the digital representation of the new electronic components based on the communication, derives the functional relationship between the replaceable and new electronic components from their digital representations, updates the digital model by replacing the digital representation of the replaceable electronic components with the digital representation of the new electronic components based on the functional relationship, and controls the biological process layout to execute the biological process based on the updated digital model.

[0013] Claim 2 provides an embodiment of the new electronic component. Generally, the new electronic component and the replaceable electronic component can be of the same type, and everything said about the new electronic component may additionally be true for some or all of the replaceable electronic components. However, in a preferred embodiment, the new electronic component is an upgraded electronic component and / or the replaceable electronic component is a conventional component. In a preferred embodiment of claim 2, some electronic components are disposable components. Disposable electronic components should be as simple as possible to minimize cost, area coverage, and environmental impact. The proposed protocol is designed to require very few resources and is therefore particularly suitable for disposable electronic components.

[0014] Claim 3 relates to a preferred communication method between the process control system and electronic components. A communication protocol is proposed that allows the process control system to query the memory portion (preferably a register) of the electronic components. To allow the process control system to communicate with electronic components it is unaware of, the use of self-describing electronic components is proposed. Therefore, it is not necessary to update the process control system before using electronic components that have not been used before.

[0015] The memory portion may vary between different new electronic components, but the description of the memory portion can be obtained at a standardized memory location (claim 4).

[0016] The preferred communication protocol is Modbus or a similar protocol (claim 5). Other protocols (e.g., Ethernet, CANIOLink) have been evaluated and can be used, but different drawbacks have been shown to be overcome by using Modbus.

[0017] Due to resource constraints, smart sensors will typically lack Ethernet capabilities and therefore cannot support higher-level protocols such as HTTP(S) or OPC-UA. Implementing Ethernet on sensor nodes is relatively expensive because it requires a processor capable of handling the TCP / IP stack, plus a MAC / PHY and additional circuitry for handling PoE or PoDL protocols for power distribution. Ethernet does not support multidrop without adding a 3-port switch to each device, further increasing costs. Chips supporting the new Single Pair Ethernet (SPE) protocols—specifically the Power on Data Line (PoDL) specification—are not yet widely available.

[0018] Interfaces for CAN (including derivatives such as CANopen and DeviceNet) are not available across all process control systems. Gateways are often used to convert between local protocols and CAN, but these are typically expensive and not supported by process control systems. IOLink does not have multipoint functionality.

[0019] Wireless protocols have low adoption rates in the bioprocessing industry, and the feasibility of long-range wireless power transmission is generally low for always-on devices. Advances have been made in RFID, SAW, and similar technologies, but there are no indications that these devices are ready for always-on sensor applications.

[0020] The embodiments of claim 6 relate to implementations of Modbus. A prudent choice is to designate the process control system as the client and the electronic components as the server. This choice may also result in backward compatibility with traditional servers.

[0021] Claim 7 relates to preferred details of the physical implementation.

[0022] Claims 8 to 12 describe preferred embodiments of plug-and-play capabilities on Modbus and how Modbus servers and clients can communicate. The proposed steps can be implemented even if conventional Modbus components are part of the network. Modbus itself does not support plug-and-play, but can be adapted as suggested to obtain plug-and-play, self-describing, low-cost electronic components.

[0023] Claims 13 through 16 focus on client-side and biological process control. Claim 13 specifies that the new electronic component and the replacement electronic component can be of the same type, or the new electronic component can be of a different type. For example, a manufacturer may have already manufactured a new model of pH sensor, and the new model can be inserted into the bus slot after the old sensor is removed. A process control system that knows the current process requires a pH sensor can automatically detect the new component, read its functional description from the corresponding memory section, and then integrate the new pH sensor into the digital model without user intervention.

[0024] The compatibility of new electronic components can be automatically checked (claim 14). The proposed method can also be used to scale up biological processes from lower to higher levels, particularly final production volumes (claim 15). When a part of the system is changed, process control can be able to use the same or slightly modified digital model. Users can be required to confirm whether the digital replacement complies with regulatory requirements (claim 16).

[0025] Another teaching of claim 17 of equal importance relates to an electronic component configured for use in the proposed method and specifically designed for the proposed method.

[0026] All explanations given for the proposed method are fully applicable.

[0027] Another teaching of claim 18, of equal importance, relates to a process control system configured for use in the proposed method.

[0028] All explanations given regarding the proposed method and the proposed electronic components are fully applicable. Attached Figure Description

[0029] In the following explanation, embodiments of the invention are described with reference to the accompanying drawings. The drawings are as follows: exist Figure 1 The diagram shows a bioprocess layout with a process control system and a bioreactor. exist Figure 2 The diagram shows the connection to the scaled-up bioreactor. Figure 1 The process control system requires user confirmation of the replacement of the digital representation of electronic components. exist Figure 3 The diagram illustrates the update of the digital model (from a) to b), and exist Figure 4 The connectors and possible system topologies of the proposed system are shown in the figure. Detailed Implementation

[0030] Figure 1 and Figure 2 A bioprocess arrangement 1 is shown, having a physical component 2 including a bioreactor 3. Figure 2 Bioreactor 3 in Figure 1 The bioreactor 3 in the diagram is much larger. This scale-up is typically completed during the development of the production process and is a good example use case for the proposed method. The physical components 2 also include several electronic components 4, such as sensors 5, mixers 6, etc. A process control system 7 is further shown, which... Figure 1 and Figure 2 The same process control system 7 is used in the middle. It is generally advantageous to be able to use the same process control system 7 for different scaling stages. It would be desirable to also use the same electronic components 4; however, this is generally not feasible. Some electronic components 4 will be single-use, and other electronic components 4, even if not single-use, cannot be used in larger systems.

[0031] Once the bioprocess layout 1 has reached production scale, the bioprocess layout 1 needs to periodically replace electronic components 4 between repetitions, or particularly for continuous processes, periodically replace electronic components 4 during production. The process control system 7 will now be described how it can effectively handle these changes and replacements of electrical components.

[0032] A method for operating a biological process arrangement 1 is proposed to perform at least one repetition of a biological process, particularly at least one repetition of a batch or continuous biological process. The biological process arrangement 1 includes physical components 2 for performing the biological process, which include at least one replaceable electronic component 8. Essentially every electronic component 4 is replaceable; this term is used herein to distinguish between the electronic component 4 at the start of an iteration of the proposed method and new electronic components 9 introduced during the execution of the proposed method. The new electronic component 9 may have the same type as the replaceable electronic component 8 and may be used as the replaceable electronic component 8 during another iteration of the method. However, the new electronic component 9 may also be an upgrade or model change of the replaceable electronic component 8.

[0033] The biological process arrangement 1 includes a process control system 7, such as the Sartorius bio-brain. The process control system 7 controls the biological process arrangement 1. The process control system 7 can measure process parameters and influence process parameters through actuators.

[0034] The process control system 7 uses a digital model 10 of the biological process arrangement 1 to control the biological process arrangement 1. Like the digital model 10 used for process flow diagrams, the digital model 10 is of all types, in which knowledge about specific components is used to control the biological process arrangement 1. Therefore, the term "model" should be interpreted broadly. Any representation of functional relationships between components or between components and the biological process is considered a model.

[0035] Digital model 10 includes a digital representation 11 of replaceable electronic components 8. The term "digital representation" should also be broadly understood to refer to any digital information about electronic components 4 that can be used to control biological processes. For digital model 10, all electronic and / or physical components 2, including the biological process arrangement 1, are not required.

[0036] The process control system 7 communicates with replaceable electronic components 8 to execute biological processes by controlling the biological process arrangement 1 based on a digital model 10.

[0037] It is recommended that replaceable electronic component 8 be removed during and / or between repetitions of the biological process and replaced with new electronic component 9. This repetition can be a repetition of the same or scaled-up biological process. The new electronic component 9 can be one or more components. The plural form will be used here, but it can be that only a single component is actually present.

[0038] The process control system 7 automatically detects the removal of the replaceable electronic component 8 (particularly by detecting that communication is no longer possible). The process control system 7 automatically detects the presence of a new electronic component 9. The process control system 7 communicates with the new electronic component 9 and retrieves the digital representation 11 of the new electronic component 9 based on the communication with the new electronic component 9. "Based on communication" means that any information retrieved from the communication is used to retrieve the digital representation 11. In particular, the digital representation 11 may be partially transmitted by the new electronic component 9, but it may also be stored in the memory of the process control system 7 or retrieved from the Internet. In a preferred embodiment, the digital representation 11 is retrieved entirely from the new electronic component 9.

[0039] The process control system 7 derives the functional relationship between the replaceable electronic component 8 and the new electronic component 9 from the digital representation 11 of the replaceable electronic component 8 and the new electronic component 9. This functional relationship could be, for example, that both components are temperature sensors 5 or that both sensors 5 are of the same type.

[0040] The process control system 7 updates the digital model 10 by replacing the digital representation 11 of the replaceable electronic component 8 with the digital representation 11 of the new electronic component 9 based on functional relationships. The process control system 7 controls the biological process arrangement 1 to execute the biological process based on the updated digital model 10. For example, a user can connect a new type of temperature sensor 5 to replace an old temperature sensor 5, and the process control system 7 automatically detects this change and is able to respond accordingly. Figure 3 The changes to digital model 10 are shown in a very illustrative way.

[0041] The new electronic component 9 may include: sensor 5 and / or actuator and / or disposable components, particularly disposable sensor 5 and / or disposable actuator; and / or electronic component 4 in direct contact with the fluid used in the biological process, such as a stirrer; and / or components that act on or sense the properties of the fluid used in the biological process, such as pH sensor 5, temperature sensor 5, cell mass sensor 5, or the like; and / or sterilizable reusable components. Everything described for the new electronic component 9 may also be true for the replaceable electronic component 8. However, it is also conceivable to upgrade from a conventional replaceable component that does not possess most of the capabilities of the new electronic component 9 to the new electronic component 9.

[0042] The details of the preferred communication mode between the process control system 7 and the new electronic component 9 will be explained below. These can be applied to some or all of the replaceable electronic components 8. Here, and preferably, the new electronic component 9 is self-describing. Thus, the process control system 7 may retrieve the digital representation 11 of the new electronic component 9 from the new electronic component 9, particularly by applying the information sent from the new electronic component 9 to a template independent of a particular new electronic component 9 (in particular, a template for all new electronic components 9).

[0043] Preferably, the new electronic component 9 includes a memory. The memory may include a writable portion and a read-only portion. Other organization of the memory is also possible. The new electronic component 9 can store process data in the readable memory portion.

[0044] The new electronic component 9 can communicate with the process control system 7 via a communication protocol (here and preferably Modbus). Via the communication protocol, the process control system 7 can, here and preferably, read the memory portion of the new electronic component 9, particularly its registers.

[0045] The new electronic component 9 can be adapted to send a memory portion description to the process control system 7 via a communication protocol. This may be the case where all new electronic components 9 include a memory portion located at the same memory address, which contains or leads to a description of other portions of the memory. Therefore, the new electronic component 9 can be self-describing. The process control system 7 can read this memory portion and apply a common template to understand what information the new electronic component 9 can provide and how to access that information. The memory may contain information such as measurement readings, units, preferred modes for displaying measurements, possible executable actions, or editable settings. The memories of different new electronic components 9 (e.g., actuators and sensors 5) can be constructed differently; however, through the memory portion description, the process control system 7 can access the memory portion without prior knowledge of the new electronic component 9.

[0046] Then, the readable memory portion is preferably subdivided into information portions. This subdivision of the memory portion is described at least in part by the memory portion description and not by the communication protocol. Therefore, the process control system 7 reads the readable memory portion based on the memory portion description. The read commands used by the process control system 7 can be part of the communication protocol, as in the case of Modbus. It should be understood that all descriptions of the communication protocol, especially the modifications to Modbus described therein, are relevant in their own merit and are independent of the use described by the process control system 7 or the electronic component 4. It is recommended to implement a self-describing data structure on top of the communication protocol (especially on top of Modbus).

[0047] Typically, preferably, this segmentation varies among different new electronic components 9, and / or the memory portion description is included in a readable memory portion at a predefined location known to the process control system 7, without the memory portion description being known. The process control system 7 can use discovery routines to detect new electronic components 9 and / or learn their memory organization.

[0048] The preferred implementation on Modbus is described below. Modbus defines 65,536 holding registers, numbered 0 to 65,535. In this document, all register addresses start from 0. Absolute addresses refer to the range 0 to 65,535, and relative addresses are offsets relative to the start of the table containing the address. Each holding register is 16 bits. Modbus function codes 3 and 16 allow reading or writing multiple holding registers in a single request / response transaction. The proposed protocol defines multiple tables. The identification table preferably always starts at register 0. The positions of all other tables are determined by the server manufacturer. The positions and lengths of the tables can be constant, i.e., they should not change unless the firmware is modified.

[0049] Dynamic tables are the only tables in which data can be modified. All other tables and strings can be read-only and constant, meaning they should not change unless the firmware is modified. This allows servers to store "wire-ready" tables that are ready to be sent without any modification. Clients can read and cache the contents of these constant tables without the risk of accidentally changing them.

[0050] Clients can use a combination of manufacturer ID, device ID, and firmware version to cache constant information in other tables. If the table layout changes, the firmware version may need to be added. Information stored in the identity table can be magic ID, protocol version, manufacturer ID, device ID, serial number (which can be unique for a given manufacturer ID and device ID), hardware version, firmware version, main table start, main table length, and / or main table CRC, as a means of checking for errors.

[0051] In general and additionally, it is generally preferred that the communication protocol is a bus (preferably fieldbus, more preferably Modbus), and / or the process control system 7 and the new electronic components 9 communicate, particularly via physical connection 12 (especially a single-cable physical connection 12 providing power and signals), preferably using the RS-485 protocol. This refers to RS-485 as specified in ANSI / TIA / EIA-485-A-1998.

[0052] All electronic components 4 on the bus can support a subset of the Modbus protocol, including RTU framing (MODBUS / RTU), function code 3 (read holding registers), function code 16 (write to multiple registers), and exceptions. Here, Modbus refers to the documents Modbus Protocol Specification V1.1b3 and Modbus Serial Line Protocol and Implementation Guide V1.02.

[0053] According to one embodiment, a process control system 7 is proposed to communicate as a Modbus client, and a new electronic component 9 to communicate as a Modbus server. Preferably, in addition to the new electronic component 9, the process control system 7 is also adapted to communicate with a conventional Modbus electronic component 4. The conventional Modbus electronic component 4 can exist on the same physical connection 12 without providing plug-and-play capability.

[0054] Preferably, if the client sends a message to the server and does not receive a response, the client will retry up to two times; if the server does not respond, the client may consider it non-responsive.

[0055] Here, and preferably, the process control uses empty, particularly zero registers and zero bytes of function code 16 as a control channel for the client to transmit information to all servers (particularly using broadcast address 0) or to a specific server (using its assigned address). The written register address is interpreted by the server with specific meaning and is ignored as invalid by conventional MODBUS / RTU servers.

[0056] Only one client device can exist on the bus, and it is typically a process control system or an embedded controller. The client can supply 24 VDC power to all server devices. The client can initiate all communication. The client may not have an address. A maximum of 32 server devices can exist on the bus. Servers may consume 24 VDC power supplied by the clients. Servers may not initiate communication; they may only respond to client requests. Each server may have a unique address.

[0057] According to one embodiment, the physical connection 12 between the process control system 7 and the new electronic component 9 specifically comprises four separate conductors 13, particularly wires (in... Figure 4 (As exemplarily shown in the example), and / or the proposed topology of physical connection 12 is a daisy chain multipoint topology or a point-to-point topology. Figure 4 The proposed preferred architecture with several electronic components 4, a physical connection 12, is shown, along with a view (here equal to a cross section) of the connector 14 of the physical connection 12, a 24 VDC power supply 15, a user interface 16, and a process control system 7.

[0058] Preferably, a four-pin IP 67 or higher connector 14 is used, where the client may include female contacts and the server may include male contacts. These pins can be organized using pins A and B for RS-485, 24VDC / range 18-30VDC, maximum 1A, GND, and ground shielding. The cable can be shielded twisted pair (STP) with at least two pairs.

[0059] The last device at each end of the daisy chain can implement a terminating resistor. Electronic component 4 and / or process control system 7 can have fault protection features in their RS-485 transceivers to handle situations where there is no driver activity on the network. Conventional RS-485 devices may require an adapter to provide this functionality.

[0060] Here, and preferably, the new electronic component 9 is automatically discovered by the process control system 7. To discover the new electronic component 9, the process control system 7 may execute a discovery routine, and the new electronic component 9 may execute an initialization routine. Preferably, during the discovery routine, the process control system 7 sets addresses for the new electronic component 9, and during the initialization routine, the new electronic component 9 sets these addresses to its own addresses.

[0061] Preferably, upon first startup, the client undergoes several tasks: • An empty write is broadcast to the holding register MSG_KEEPALIVE every 100ms for 3 seconds; • Inspect the legacy server at the reserved fixed address; • Discover servers and assign addresses; • Broadcast an empty write to the holding register MSG_ONLINE.

[0062] To discover a legacy server at a reserved fixed address, the client sequentially reads a holding register at address 0 for the reserved fixed server address (if any). New electronic components 9 on the server must not respond, as they do not yet have an address. The legacy server will respond with a normal or abnormal response—it doesn't matter as long as "ping" returns. In this way, the client checks for connections to any existing legacy servers.

[0063] According to one embodiment, during a discovery routine, the process control system 7 broadcasts an initialization message, specifically a null write request, and then sends a read request at an address that has not yet been assigned. Upon detecting the broadcast initialization message, new electronic components 9 respond to the read request at addresses that have not been assigned to them.

[0064] This could be as follows: During the discovery routine, the process control system 7 addresses multiple (especially all) new electronic components 9 that have not yet immediately executed the discovery routine using an initialization request (specifically a Modbus slot read request). Preferably, the initialization request contains one of several possible initialization IDs, specifically the Modbus slot number as part of the Modbus slot read request, and the new electronic component 9 has an assigned (specifically random) initialization ID, specifically the Modbus slot number. Among the addressed new electronic components 9, only the electronic component with a matching initialization ID executes the discovery routine.

[0065] The discovery routine can run when the network is powered on, and the interval at which it runs is determined by the client. In this way, the client learns about new servers. The preferred discovery routine is now described. When the server powers on, it has no address (ignoring 247 and broadcasts) and assigns itself to one of several (e.g., 32) “slots” using, for example, the least significant 5 bits of its serial number. This greatly reduces and can potentially eliminate bus contention, especially when only a few devices are present. For each slot, the client broadcasts an empty write to the holding register MSG_SLOTx (where x is the slot number) and then reads the manufacturer ID + device ID + serial number, preferably starting from 1, found in holding registers 2-7 (six registers = 96 bits) at the address of the next unoccupied server. There are three possible outcomes: 1. No server is in the slot, the client did not receive a response, and a timeout occurred. The client skips to the next slot; 2. There is a server in the slot, and the client receives a correctly formatted response. The client writes the Manufacturer ID + Device ID + Serial Number back to holding registers 2-7 on the unoccupied server address. The server checks if its Manufacturer ID + Device ID + Serial Number matches, and if a match is found, it obtains the server address and sends a normal write response. A correct response from the server indicates that the address has been successfully allocated, so the client moves to the next unoccupied server address and retrys. If no response is received, the client moves to the next slot; 3. Since there are multiple servers in the slot, a garbled response (erroneous CRC) is received. Exponential backoff is then used to obtain a clear reading between competing devices. The client extends its timeout to 1 second. The client retransmits the slot number, adding a random 0ms or 1ms delay to each server. If garbled characters reappear, the client retransmits the slot number, adding a random 0ms, 1ms, or 2ms delay to each server. This continues in the order of 1, 2, 4, 8, ... 512. This may continue until the client receives a clear response. Once a clear response is received, the client returns to its usual 100ms timeout. The client then moves to the next available server address and tries again until no response is received. The client then moves to the next slot.

[0066] Because this is a lengthy operation lasting several seconds, it is inconvenient to interrupt normal network traffic after the initial configuration. Clients can interleave the discovery routine with other low-priority traffic. Clients can send an empty write to the holding register MSG_RELEASEADDR at a single server address, forcing it to relinquish its automatically assigned address. Clients can also broadcast an empty write to the holding register MSG_RELEASEADDR, forcing all servers to relinquish their automatically assigned addresses. For traditional clients that need to configure servers to a new server address that is retained through power failure, the client can send an empty write to the holding register MSG_RETAINADDR at a single server address. The automatically assigned server address will be used until the server receives the MSG_RELEASEADDR message.

[0067] More generally, according to one embodiment, the process control system 7 is proposed to iterate through possible initialization IDs, and / or, if several new electronic components 9 immediately respond to the initialization request, the process control system 7 repeats the initialization request, and the responding new electronic components 9 follow a conflict avoidance strategy (in particular by adding random delays to the repeated responses).

[0068] According to one embodiment, a new electronic component 9 is proposed to set the baud rate for communication via baud rate cycling, and / or a new electronic component 9 is proposed to use the Modbus 8N1 serial format.

[0069] In a traditional MODBUS / RTU over an RS-485 network, each device has three settings that must be configured before communication begins: • Data rate – also known as baud rate, is measured in bits per second (bps) and is typically one of 9600, 19200, 38400, or 57600 bps. The data rate can be any value supported by the cable type, cable length, and UART capability. The Modbus serial specification requires support for 9600 and 19200 bps (default). • Serial format – number of data bits, parity type, and number of stop bits. The Modbus serial specification requires 8E1 and recommends 8N2 to maintain an 11-bit frame; • Address – Each server must have a unique address.

[0070] Configuring these settings on traditional equipment can be extremely challenging because they may require specialized software, adapter cables, DIP switch settings, and so on.

[0071] To achieve plug-and-play capability, the bus proposed in one embodiment is simplified through flexibility: • Data rate – The client defaults to 115200 bps, but for compatibility with legacy servers, it can be overwritten to 9600 or 19200 bps. The server must automatically detect the data rate upon power-up, first by searching for “magic frames” from MSG_KEEPALIVE errors caused by baud rate errors, and then by looping through the baud rate until a properly formatted packet arrives; • Serial format – fixed at 8 data bits, no parity, and 1 stop bit (8N1), as this is the format commonly used in industrial serial communication. Any legacy server that cannot be configured for 8N1 will require an adapter or a separate bus. This setup creates a 10-bit frame; while strictly speaking, this deviates from the Modbus serial specification, it is common practice in industrial settings because parity adds little value and frame integrity is already protected by CRC. • Address – The client automatically assigns an available address to the server, and optionally reserves a fixed address for a legacy server.

[0072] The Modbus protocol specifies a minimum inter-frame delay but not a maximum. Since the time between frames is a key driver of the overall frame rate, the protocol proposed in one embodiment establishes additional timing constraints. The client's timeout value (i.e., if no character is received within this time, it can retry or consider the server unresponsive) can be set to 10ms unless a slower legacy server exists. A processing window exists between the moment when the end of the request frame can be detected (after t1.5) and the moment when response frame transmission can begin (after t3.5); this is 2.08ms at 9600bps, 1.04ms at 19200bps, and 1.00ms at higher data rates. The server device must begin transmitting a response no more than 5ms after receiving the last character of the request. The server must have sufficient processing power and efficient execution flow (e.g., using interrupts instead of blocking calls) to keep up with the speed. Preliminary feasibility tests using an ARM Cortex-M0+ processor running FreeRTOS with a system clock frequency of 1ms show that it can easily maintain a processing window of less than 2ms.

[0073] Returning to a more general process view, preferably, at least one replaceable electronic component 8 and at least one new electronic component 9 replacing the replaceable electronic component 8 in the biological process are of the same type, i.e., generally the same, and / or, at least one replaceable electronic component 8 and at least one new electronic component 9 replacing the replaceable electronic component 8 in the biological process are of different types, and / or, at least one additional new electronic component 9 does not replace any of the replaceable electronic components 8. The proposed embodiments are particularly suitable for replacing replaceable electronic components 8 (e.g., temperature sensor 5) with newer, more capable, more accurate, or similar new electronic components 9, even new electronic components 9 from other manufacturers.

[0074] According to another preferred embodiment, the process control system 7 receives compatibility data from the new electronic component 9, such as functional data, limits, calibration data, or the like, and checks the compatibility of the new electronic component 9 with other existing electronic components 4 and / or the process control system 7 and / or the biological process. Additionally or alternatively, the process control system 7 may receive documentation data, particularly verification data, from the new electronic component 9 and record the replacement of the electronic component 4. In the current field, maintaining an audit trail may be particularly important. Therefore, automatically supporting such an audit trail is advantageous. Additionally or alternatively, the process control system 7 may receive graphical user interface data and / or documentation and / or links to documentation and / or multi-language data related to the presentation of data received from the new electronic component 9.

[0075] According to one embodiment, several electronic components 4 are proposed to be replaced simultaneously along with other disposable components, particularly between repetitions of a biological process. For example, a disposable bioreactor 3 having several sensors 5 and actuators can be replaced once. Here, and preferably, and as in Figure 1 and Figure 2 As demonstrated above, the repetition of biological processes can include repetitions with different (especially increased) liquid volumes.

[0076] According to one embodiment, a process control system 7 is proposed to prompt the user before replacing the digital representation 11 of replaceable electronic component 8 with the digital representation 11 of new electronic component 9.

[0077] For example, a disposable bioreactor 3 with a set of sensors 5 is removed, a new bioreactor 3 is implemented, some sensors 5 are replaced with new disposable and / or sterilized reusable sensors 5, or have the same model or similar model, the digital control model is automatically updated, and the user can accept automatic detection and start a new iteration with a single click.

[0078] Another equally important teaching relates to electronic component 4, configured to function as novel electronic component 9 in the proposed method. Electronic component 4 may have a processor and memory, and may have no other communication capabilities besides the proposed communication capabilities.

[0079] All explanations given for the proposed method are fully applicable.

[0080] Another equally important teaching relates to the process control system 7 configured for use in the proposed method.

[0081] All explanations given regarding the proposed method and the proposed electronic component 4 are fully applicable.

Claims

1. A method of operating a biological process arrangement (1) to perform at least one repetition of a biological process, wherein the biological process arrangement (1) includes physical components (2) for performing the biological process, wherein the physical components (2) include at least one replaceable electronic component (8), wherein the biological process arrangement (1) includes a process control system (7), wherein the process control system (7) controls the biological process arrangement (1). The process control system (7) uses a digital model (10) of the biological process arrangement (1) to control the biological process arrangement (1), wherein the digital model (10) includes a digital representation (11) of replaceable electronic components (8), and the process control system (7) communicates with the replaceable electronic components (8) to execute the biological process by controlling the biological process arrangement (1) based on the digital model (10). Its features Replaceable electronic components (8) are removed and replaced by new electronic components (9) during and / or between repetitions of the biological process. The process control system (7) automatically detects the removal of replaceable electronic components (8), automatically detects the presence of new electronic components (9), communicates with new electronic components (9), retrieves the digital representation (11) of new electronic components (9) based on the communication with new electronic components (9), derives the functional relationship between replaceable electronic components (8) and new electronic components (9) from the digital representations (11) of replaceable electronic components (8) and new electronic components (9), replaces the digital representation (11) of replaceable electronic components (8) with the digital representation (11) of new electronic components (9) based on the functional relationship, thereby updating the digital model (10), and the process control system (7) controls the biological process arrangement (1) to execute the biological process based on the updated digital model (10).

2. The method of claim 1, wherein, The new electronic component (9) includes: a sensor (5) and / or an actuator and / or a disposable component, particularly a disposable sensor (5) and / or a disposable actuator; and / or an electronic component (4) that comes into direct contact with the fluid used in the biological process; and / or a component that acts on or senses the properties of the fluid used in the biological process; and / or a sterilizable reusable component.

3. The method according to claim 1 or 2, characterized in that, The new electronic component (9) includes a memory, which stores process data in a readable memory portion. The new electronic component (9) communicates with the process control system (7) via a communication protocol. The process control system (7) can read the memory portion of the new electronic component (9), especially the registers, via the communication protocol. The new electronic component (9) sends a memory portion description to the process control system (7) via the communication protocol. The readable memory portion is subdivided into information portions. The subdivision of the memory portion is described at least in part by the memory portion and not by the communication protocol. The process control system (7) reads the readable memory portion based on the memory portion description.

4. The method of claim 3, wherein, The subdivision varies between different new electronic components (9), and / or the memory portion description is included in a readable memory portion at a predefined location known to the process control system (7), without the memory portion description being known.

5. The method according to claim 3 or 4, characterized in that, The communication protocol is a bus, preferably a fieldbus, more preferably a Modbus, and / or the process control system (7) and the new electronic components (9) communicate via a physical connection (12), particularly a physical connection (12) that provides power and signals, preferably using the RS-485 protocol.

6. The method of claim 5, wherein, The process control system (7) communicates as a Modbus client and the new electronic component (9) communicates as a Modbus server. Preferably, in addition to the new electronic component (9), the process control system (7) is also adapted to communicate with the conventional Modbus electronic component (4).

7. The method according to claim 5 or 6, characterized in that, The physical connection (12) between the process control system (7) and the new electronic component (9) specifically includes four separate conductors (13), especially wires, and / or the topology of the physical connection (12) is a daisy chain multipoint topology or a point-to-point topology.

8. The method according to one of claims 5 to 7, characterized in that, The new electronic component (9) is automatically discovered by the process control system (7). In order to discover the new electronic component (9), the process control system (7) executes a discovery routine and the new electronic component (9) executes an initialization routine. Preferably, during the discovery routine, the process control system (7) sets an address for the new electronic component (9) and during the initialization routine, the new electronic component (9) sets its address to its address.

9. The method of claim 8, wherein, During the discovery routine, the process control system (7) broadcasts an initialization message, in particular a write request, and then sends a read request at an address that has not yet been assigned. After the broadcast initialization message is detected, new electronic components (9) respond to the read request at addresses that have not been assigned to them.

10. The method according to claim 8 or 9, characterized in that, During the discovery routine, the process control system (7) addresses multiple, in particular all, new electronic components (9) that have not yet immediately executed the discovery routine using initialization requests, particularly Modbus slot read requests. Preferably, the initialization request contains one of several possible initialization IDs, particularly the Modbus slot number as part of the Modbus slot read request, and the new electronic components (9) have assigned, in particular random, initialization IDs, particularly the Modbus slot number. Among the addressed new electronic components (9), only the electronic component with a matching initialization ID executes the discovery routine.

11. The method of claim 10, wherein, The process control system (7) iterates through possible initialization IDs, and / or, if several new electronic components (9) respond immediately to the initialization request, the process control system (7) repeats the initialization request, and the responding new electronic components (9) follow a conflict avoidance strategy in particular by adding random delays to the repeated responses.

12. The method according to any one of claims 5 to 11, characterized in that, The new electronic component (9) sets the baud rate for communication via baud rate cycling, and / or the new electronic component (9) uses the Modbus 8N1 serial format.

13. The method according to any of the preceding claims, characterized in that, At least one replaceable electronic component (8) and at least one new electronic component (9) replacing the replaceable electronic component (8) in a biological process are of the same type, and / or, at least one replaceable electronic component (8) and at least one new electronic component (9) replacing the replaceable electronic component (8) in a biological process are of different types, and / or, at least one new electronic component (9) does not replace any of the replaceable electronic components (8).

14. The method according to one of the preceding claims, characterized in that, The process control system (7) receives compatibility data from the new electronic component (9) and checks the compatibility of the new electronic component (9) with other existing electronic components (4) and / or the process control system (7) and / or the biological process, and / or the process control system (7) receives documentation data, especially verification data, from the new electronic component (9) and records the replacement of the electronic component (4).

15. The method according to any of the preceding claims, characterized in that, Several electronic components (4) are replaced simultaneously along with other disposable components, particularly between repetitions of biological processes, preferably repetitions of biological processes including repetitions with different, particularly increased, liquid volumes.

16. The method according to one of the preceding claims, characterized in that The process control system (7) asks the user before replacing the digital display (11) of the replaceable electronic component (8) with the digital display (11) of the new electronic component (9).

17. An electronic component configured to be used as a new electronic component (9) in the method according to any one of claims 3 to 12.

18. A process control system configured for use in the method according to any one of claims 1 to 16.

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