PROCESS MONITORING DEVICE

Description

[0001] The invention relates to a process monitoring device for pharmaceutical bioprocess applications.

[0002] Systems for bioprocess applications - examples of which are bioreactors or crossflow systems - are used to receive, store and / or mix biological media, which comprise fluids and / or solids. The biological media are usually provided in disposable containers and / or bags and introduced into a housing of the system for bioprocess applications, where they are stored, temperature-controlled and / or mixed. In such a system for bioprocess applications, the process properties of the biological media are examined and / or monitored using various sensors. One or more sensors can be arranged on the system for bioprocess applications, with which measurements are taken on the medium in the disposable container or in the tubing system, such as temperature or pH measurements.The sensor is mounted on an outer surface of the housing of the bioprocessing system in such a way that a medium-contacting portion of the sensor penetrates the housing wall of the bioprocessing system into the container and the medium. Alternatively, the sensors can be integrated into a hose system designed to remove the medium from the container. This hose system is typically mounted on the outer surface of the housing. Depending on the application, the bioprocessing system is handled in a sterile environment or under cleanroom conditions.

[0003] DE 10 2016 008 655 A1 discloses a system for biotechnological applications, in particular a bioreactor, which has system rails or supports on the outer surface of the housing for attaching tubes and sensors to the exterior of the housing. Triclamps are also disclosed as fastening means.

[0004] Coriolis flowmeters are typically used in process-automated industrial plants in pipelines via connecting devices such as flanges, connecting pieces, etc. An example of this is a filling station for liquid or gaseous substances, as disclosed in DE 10 2006 013 826 A1, or a process line as disclosed in DE 10 2017 128 565 A1.

[0005] Coriolis flowmeters with replaceable disposable measuring tube modules suitable for single-use applications are also known. For example, WO 2011 / 099989 A1 discloses a method for producing a monolithic measuring tube module of a Coriolis flowmeter with curved measuring tubes. The measuring tube body of each measuring tube is first formed from a solid polymer, and the channel for conducting the flowable medium is then machined into the module. WO 2011 / 099989 A1, like US Pat. No. 10,209,113 B2, teaches a modular design of the Coriolis flowmeter, which enables the replacement of the medium-contacting part of the measuring device.

[0006] US 2020 / 0116612 A1 presents a Coriolis flowmeter with disposable tubing and a reusable measuring device. The Coriolis flowmeter is used to measure the liquid flow from a bioprocess unit.

[0007] To date, nothing is known about the integration of Coriolis flowmeters into process monitoring systems for pharmaceutical bioprocess applications. The invention aims to remedy this situation.

[0008] The object is achieved by the process monitoring device according to claim 1.

[0009] The process monitoring device according to the invention, preferably for pharmaceutical bioprocess applications, comprising: a measuring tube module, wherein the measuring tube module comprises at least one measuring tube through which a medium can flow, wherein the measuring tube module has a first vibration exciter component of at least one vibration exciter, which is designed to excite the measuring tube module, in particular the at least one measuring tube, to vibrate, wherein the measuring tube module has a first vibration sensor component of at least one vibration sensor, which is designed to detect the vibrations of the at least one measuring tube, a receiving module, wherein the receiving module has a receptacle, wherein the measuring tube module can be inserted into the receptacle, wherein the measuring tube module can be mechanically separably connected to the receiving module, wherein the receiving module has a second vibration exciter component of the at least one vibration exciter, wherein the receiving module has a second vibration sensor component of the at least one vibration sensor;and a system for biotechnical applications, wherein the system comprises a housing, wherein the housing has a housing wall which delimits a housing interior, wherein the housing wall has a cover, wherein the cover has an opening, wherein the receiving module, in particular the receptacle, extends through the opening into the housing interior. ;

[0010] The arrangement of the receiving module according to the invention has the advantage that it enables a compact design of the process monitoring device and minimizes external mechanical interference with the flow measurement. The compact design also means that the measured values ​​determined - such as temperature - only differ insignificantly between any sensors used, so that The use of a measuring tube module in conjunction with a receiving module for determining a measured variable dependent on the mass flow rate of the flowable medium has the advantage that it provides an alternative to the scales usually used in pharmaceutical bioprocess applications for determining the quantities of medium used. The housing preferably has a metallic housing wall, which is preferably designed as a sheet metal part. The receiving module body is made of solid steel in order to enable the measuring tubes to oscillate with as little interference as possible.

[0011] Advantageous embodiments of the invention are the subject of the subclaims.

[0012] One embodiment provides that the receiving module has a section wherein the section is located outside the housing interior, wherein the receiving module has a particularly circumferential shoulder in the section, wherein the cover has a cover surface, wherein the shoulder has a shoulder surface, wherein the shoulder surface and the cover surface face each other.

[0013] By providing a shoulder on the receiving module, a counter surface is created for securing the receiving module via the fastening arrangement, which is preferably arranged on the inside of the housing. A sealing means is preferably arranged between the shoulder surface and the cover surface to seal the receiving module and prevent liquids from entering the housing interior during cleaning of the system.

[0014] One embodiment provides that the receptacle extends in a receiving direction, wherein the receiving module is arranged in the opening such that the receiving direction has a vectorial component with a direction opposite to a gravitational direction.

[0015] The special arrangement has the advantage of making the measuring tubes self-draining. The inclination of the holder relative to a horizontal reference axis allows the medium contained in the measuring tube to flow out. The inclination is based on the ASME BPE GSD1 to GSD3 (2019) standard.

[0016] One embodiment provides that the receiving module comprises a fastening arrangement, wherein the fastening arrangement is arranged in the housing interior, wherein the fastening arrangement is configured to mechanically connect the receiving module to the cover.

[0017] The advantage of this design is that it allows for better cleaning from the outside of the enclosure, as the mounting assembly is located entirely inside the enclosure. No additional openings in the cover mean fewer places where moisture can enter the enclosure.

[0018] One embodiment provides that the fastening arrangement comprises a first fastening means, wherein the first fastening means is movably connected to the receiving module, in particular in a guide, wherein the fastening arrangement comprises a second fastening means, wherein the first fastening means is in effect with the second fastening means.

[0019] One embodiment provides that the cover has a rear side, wherein the second fastening means is designed to bend the first fastening means at least partially, preferably opposite to the rear side.

[0020] One embodiment provides that the plant comprises a single-use plant, in particular a bioreactor, a plant for chromatographic purification processes, a crossflow plant or similar.

[0021] A bioreactor, or fermentation reactor, is a container in which biological processes take place under controlled, predefined conditions, or in which specific cultures are cultivated in a medium. The use of a bioreactor is an important component of pharmaceutical bioprocess technology. The containers can be arranged in a housing, and the process properties of the medium can be monitored using sensors.

[0022] Chromatography is a process that allows the separation of a mixture of substances based on the different distribution of its individual components between a stationary and a mobile phase. This is used, for example, in production for the purification of substances, particularly in the manufacture of biopharmaceuticals. Cross-flow filtration is another method for filtering media.

[0023] One embodiment provides that at least the measuring tube module and the receiving module form a modular Coriolis flowmeter.

[0024] Coriolis flowmeters are known for their very high measurement accuracy and, in addition to the mass flow, can also provide information on the viscosity and density of the medium being conveyed. This is not possible with conventional weight scales.

[0025] The invention is explained in more detail with reference to the following figures. It shows: Fig. 1 : a process monitoring device according to the invention; Fig. 2A-C : three views of a measuring tube and recording module; Fig. 3A-B : a partially sectioned interior view of the process monitoring device with a first embodiment of the fastening arrangement and a side view of the first embodiment of the fastening arrangement; Fig. 4 : a partially sectioned interior view of the process monitoring device with a second embodiment of the fastening arrangement; Fig. 5 : a side view of the first fastening means of the second embodiment of the fastening arrangement 84.

[0026] The Fig. 1 shows a process monitoring device according to the invention for pharmaceutical bioprocess applications in a plant for biotechnological applications 74. A measuring tube module 4 and a receiving module 16 together form a Coriolis flowmeter 2. The measuring tube module 4 has at least one measuring tube 3 through which a medium can flow and is configured as an exchangeable component of the Coriolis flowmeter 2. For this purpose, it preferably has no electronic components that must be supplied with a voltage source via an electrical contact. The measuring tube module 4 has a first vibration exciter component of at least one vibration exciter, which is configured to excite the measuring tube module 4, in particular the at least one measuring tube 3, to vibrate.In addition, the measuring tube module 4 has a first vibration sensor component of at least one vibration sensor, which is configured to detect the vibrations of the at least one measuring tube 3. The first vibration exciter component and the first vibration sensor component are preferably magnets. Furthermore, the measuring tube module 4 has process connections 30, which are also designed as distributor pieces.

[0027] The receiving module 16 is an integral part of the system for biotechnological applications 74 and comprises the electronic components with which the Coriolis flowmeter 2 is operated and the flow-dependent measurement signal is recorded. The receiving module 16 has a receptacle 23 for the measuring tube module 4, into which the measuring tube module 4 can be inserted. In addition, the measuring tube module 4 can be mechanically separated or detachably connected to the receiving module 16 to ensure user-friendly replacement of the measuring tube module 4. When changing the application, the measuring tube module 4 can be replaced with a new, sterilized measuring tube module 4. The receiving module 16 has a second vibration exciter component of the at least one vibration exciter and a second vibration sensor component of the at least one vibration sensor.These are the excitation coil and at least one sensor coil, each of which is electrically connected to a measuring circuit and controlled and measured by it. The receiving module 16 is not designed to come into contact with the medium, but is designed to be cleanable.

[0028] The system 74 for biotechnological applications has a housing 75 with a housing wall 76, which defines a housing interior. The housing wall 76 is made of sheet metal. The receiving module 16 is arranged in an opening in the housing wall 76. The receiving module 16, in particular the receptacle of the receiving module 16, extends through the opening 79 into the housing interior. The receiving module 16 is fastened through the housing interior (see Figs. 3-6). The receiving module 23 can be arranged in the opening 79 such that the receiving direction—which is defined by the direction of extension of the receiving module—has a vectorial component with a direction opposite to a gravitational direction. The system 74 can comprise a bioreactor, a system for chromatographic purification processes, a crossflow system, or the like.

[0029] The Fig. 2A-C show a series of images of individual assembly steps of a measuring device 2 according to the invention. The measuring tube module 4 comprises two measuring tubes 3.1, 3.2, which are mechanically coupled to one another via a coupler arrangement 1. In the embodiment shown, the coupler arrangement 1 comprises six coupler elements 6, which partially encompass the two measuring tubes 3.1, 3.2. The measuring tube module 4 is designed as a disposable article and can be mechanically detachably arranged and fastened in a provided receiving module 16. The two measuring tubes 3.1, 3.2 each comprise a measuring tube body, which is at least partially made of steel. An excitation magnet 36 and two sensor magnets 38.1, 38.2 are each attached to the measuring tube bodies. The receiving module 16 has a receptacle 23, which extends from a front surface of the receiving module body 22 in the longitudinal direction thereof.In addition, the receiving module body 22 of the receiving module 16 has a mounting surface 26 on which the measuring tube module 4, in particular the fixing body arrangement 35, rests in the installed state, and which is designed such that the measuring tubes 3.1, 3.2 of the measuring tube module 4 do not touch the wall of the receiving module 16. The mounting surface 26 encloses the receptacle 29 in a cross-section, so that when the measuring tube module 4 is arranged, an entire edge region of the fixing body arrangement 35 rests on the mounting surface 26. The two excitation coils of the vibration exciter and the four sensor coils of the vibration sensor (not shown) are arranged in an inner circumferential surface of the receiving module 16, in particular distributed on two diametrically oriented side surfaces of the receptacle 23. The excitation coils and vibration coils are preferably embedded in the receiving module body 22 so that they are not damaged when the measuring tube module 4 is inserted.

[0030] When installed, the measuring tube module 4 is arranged in the receptacle 23 and the fixing body arrangement 35 rests on the mounting surface 26. The measuring tube module 4 is now ready to be attached to the receiving module 16 by means of the fixing device 34. This is necessary to enable a measurement with a stable zero point. For this purpose, the fixing device 34 has a first fixing element 40 and a second fixing element 41, each of which is designed to be pivotable and has a fixing surface 42, 43. The fixing surfaces 42, 43 are each located at a first end of the fixing element 40, 41. The fixing elements 40, 41 each have an elongated fixing element body. In the end section encompassing the first end, the fixing elements 40, 41 are attached to the receiving module body 22 so as to be pivotable about a rotation axis.The fixing elements 40, 41 are configured to press the fixing body arrangement 44 against the mounting surface 26, thereby suppressing movements of the fixing body arrangement. The first fixing element 40 is connected to a pivotable connecting device 46, which comprises a connecting body 47. The connection between the fixing element 40 and the pivotable connecting device 46 is located at the second end of the first fixing element 40. The connecting body 47 is at least partially cubic and cylindrical in its end section. A locking device 48 is arranged there on the connecting body 47. In the illustrated embodiment, the end section of the connecting body 47 has an external thread, and the locking device 48 is designed as a screw.Depending on the application and the requirements for measurement performance, the locking device 48 can also be designed as a torque screw, a clamping lever, a tensioning bracket, a tensioner, a quick-release device, a tensioning lever, a clamping claw, a hood closure and / or an eccentric lever. Alternatively (not shown), the locking device 48 can be designed as a buckle, in particular a cuff buckle, which is arranged on a first fixing element 40 of the two fixing elements 40, 41. Accordingly, a pivoting part is arranged on the second fixing element 41. The pivoting part is designed as a cuff pivoting part which has at least one hook, in particular a cuff hook. In the fixed state, the fixing surfaces 42, 43 of the fixing elements 40, 41 touch the support surfaces 44, 45 of the fixing body arrangement 35. The connecting body 47 of the connecting device 46 interacts with the second fixing element 41, i.e.The connecting device 46, in particular the connecting body 47, connects the first fixing element 40 to the second fixing element 41. The second fixing element 41 has a guide 51 for the end section of the connecting body 47 at its second end. In the closed state, the connecting body 47 extends along the guide 51 of the second fixing element 41. The locking device 48 contacts the clamping surface 49 of the second fixing element 41. When the locking device 48—in the form of a screw—is tightened, the two fixing elements are brought closer together. The locking device 48 presses against the clamping surface 49. Because the two fixing elements 40, 41 are designed to pivot about a rotation axis, the tightening and corresponding approach of the fixing elements 40, 41 exerts a force on the fixing body arrangement 35 parallel to the longitudinal direction of the measuring tube module 4 in the direction of the mounting surface 26.This force ensures uniform attachment of the measuring tube module 4 to the carrier unit body 22. The measuring tubes 3.1, 3.2 each have an inlet longitudinal axis in the inlet section and an outlet longitudinal axis in the outlet section, wherein a first longitudinal plane runs through the inlet longitudinal axes of the measuring tubes, wherein a second longitudinal plane runs through the outlet longitudinal axes of the measuring tubes, wherein the fixing body arrangement 35 has a second end face which is oriented opposite to the first end face, wherein the first longitudinal plane and the second longitudinal plane delimit a first surface on the second end face of the fixing body arrangement 35, wherein the inlet longitudinal axis and the outlet longitudinal axis of the first measuring tube 3.1 run in a third longitudinal plane, wherein the inlet longitudinal axis and the outlet longitudinal axis of the second measuring tube 3.2 extend in a fourth longitudinal plane, wherein the third longitudinal plane and the fourth longitudinal plane on the second end face delimit a second surface, wherein in the fastened state the fixing surfaces 42, 43 of the fixing elements 40, 41 rest, in particular, exclusively on the first surface and thereby lie outside the second surface. Alternatively, the fixing body arrangement 35 can be designed in several parts, wherein one part is materially connected to the at least one measuring tube 3.1, 3.2 and a further part is attached at least form-fitting. This further part is designed and configured to serve as a process connection for the measuring tubes 3.1, 3.2 to a process line. For this purpose, the further part can, for example, have standardized process connections, such as flanges or threads.

[0031] The Fig. 3A und B show a partially sectioned interior view of the process monitoring device with a first embodiment of the fastening arrangement 84 for fastening the receiving module 16 to the housing wall, in particular to the cover 78, and a side view of the first embodiment of the fastening arrangement 84. An opening 79, in which the receiving module 16 is arranged, is incorporated in the cover 78. The receiving module 16, in particular the receptacle 23, extends through the opening 79 into the housing interior 77 of the housing. In addition to the receiving module 16, pumps, fans, cables, hoses, electronic components and containers for the medium can be located in the housing interior 77. Furthermore, the receiving module 16 has, in the receiving section 80, a particularly circumferential shoulder 81 with a shoulder surface 83. A cover surface 82 of the cover 78 and the shoulder surface 83 face one another and lie on top of one another in the installed state.The shoulder is shown schematically and is generally significantly thicker than the cover 78. The fastening is realized via a fastening arrangement 84 which is arranged in the housing interior 77. The fastening arrangement 84 is designed to mechanically connect the receiving module 16 to the cover 78. For this purpose, it has a first fastening means 85 and a second fastening means 86. The first fastening means 85 is connected to the receiving module 16 and the second fastening means 86 is connected to the first fastening means 85 such that they interact with one another. The rear side 88 of the cover 78 is in contact with the second fastening means 86, which is designed to bend the first fastening means 85 at least partially, preferably opposite to the rear side 88.For this purpose, the first fastening means 85 has a first leg 89 and a second leg 90, which run essentially parallel to one another and are spaced apart. The second fastening means 86, in the illustrated embodiment, comprises a screw which extends between the first leg 89 and the second leg 90 in a threaded opening. According to the illustrated embodiment, the first fastening means 85 is fastened to the receiving module body 22 by means of a screw. As an alternative to the two legs, a single plate with a blind hole and a thread can also be provided. The receiving module body 22 preferably comprises steel.

[0032] The Fig. 4 shows a partially sectioned interior view of the process monitoring device with a second embodiment of the fastening arrangement 84. The second embodiment differs from the first embodiment essentially by the additional guide 87, which is incorporated in the receiving module body 22. The shape of the first fastening means 85 allows the fastening arrangement 84 to be arranged movably in the longitudinal direction of the receiving module 16. The guide 87 is designed as a T-slot, and the body of the first fastening means 85 is correspondingly designed to complement it in sections (see Fig. 5 ). The first fastening means 85 can also be connected to the receiving module body 22 in a form-fitting and / or force-fitting manner via a screw. In this case, no threaded openings need to be provided in the receiving module body 22. Instead, the first fastening means 85 can be clamped in the guide by bracing the base body.

[0033] The Fig. 5 shows a perspective view of the first fastening means 85 of the second embodiment of the fastening arrangement 84. The first fastening means 85 has a T-shaped basic shape in cross-section, at least in one end section. This is designed to complement the shape of the guide. The base body of the first fastening means 85 preferably comprises steel. Bezugszeichenliste

[0034] Coupler assembly 1 Coriolis flowmeter 2 Measuring tube 3 Measuring tube module 4 Coupler element 6 Receptacle module 16 Hose and / or plastic pipe system 17 Process monitoring unit 19 Receptacle module body 22 Receptacle 23 Mounting surface 26 Process connection 30 Fixing device 34 Fixing body assembly 35 Excitation magnet 36 Sensor magnet 38 First fixing element 40 Second fixing element 41 Fixing surface 42 Fixing surface 43 Support surface 44 Support surface 45 Connecting device 46 Connecting body 47 Closing device 48 Clamping surface 49 Guide 51 System for biotechnological applications 74 Housing 75 Housing wall 76 Housing interior 77 Cover 78 Opening 79 Receptacle section 80 Shoulder 81 Cover surface 82 Shoulder surface 83 Fastening assembly 84 First fastening means 85 Second fastening means 86 Guide 87 Back 88 First leg 89 second leg 90

Claims

1. A process monitoring device, preferably for pharmaceutical bioprocess applications, comprising: - a measuring tube module (4), wherein the measuring tube module (4) comprises at least one measuring tube (3) through which a medium can flow, wherein the measuring tube module (4) has a first vibration exciter component of at least one vibration exciter which is set up to excite the measuring tube module (4), in particular the at least one measuring tube (3), to vibrate, wherein the measuring tube module (4) has a first vibration sensor component of at least one vibration sensor, which is set up to detect the vibrations of the at least one measuring tube (3), - a recording module (16), wherein the receiving module (16) has a receptacle (23), wherein the measuring tube module (4) can be inserted into the receptacle (23), wherein the measuring tube module (4) can be mechanically disconnected from the receiving module (16), wherein the receiving module (16) comprises a second vibration exciter component of the at least one vibration exciter, wherein the receiving module (16) comprises a second vibration sensor component of the at least one vibration sensor; and - a plant (74) for biotechnical applications, wherein the system (74) has a housing (75), wherein the housing (75) has a housing wall (76) which delimits an interior (77) of the housing, wherein the housing wall (76) has a cover (78), wherein the cover (78) has an opening (79), wherein the receptacle module (16), in particular the receptacle (23), extends through the opening (79) into the interior (77) of the housing.

2. Process monitoring device according to claim 1, wherein the receiving module (16) has a receiving section (80) outside the interior (77) of the housing, wherein the receiving module (16) has a particularly circumferential shoulder (81) in the receiving section (80), wherein the cover (78) has a covering surface (82), wherein the heel (81) has a heel surface (83), wherein the heel surface (83) and the cover surface (82) face each other.

3. Process monitoring device according to claim 1 and / or 2, wherein the receptacle (23) in a receiving direction, wherein the pick-up module (23) is arranged in the opening (79) such that the pick-up direction has a vectorial portion with a direction opposite to a gravitational direction.

4. Process monitoring device according to at least one of the preceding claims, wherein the receiving module (16) comprises a fastening arrangement (84), wherein the fastening arrangement (84) is arranged inside the housing (77), wherein the fastening arrangement (84) is designed to mechanically connect the receiving module (16) to the cover (78).

5. Process monitoring device according to claim 4, wherein the fastening arrangement (84) comprises a first fastening means (85), wherein the first fastening means (85) is movably connected to the receiving module (16), in particular in a guide (87) wherein the fastening arrangement (84) comprises a second fastening means (86), wherein the first fastening means (85) is in action with the second fastening means (86).

6. Process monitoring device according to claim 5, wherein the cover (78) has a rear side (88), wherein the second fastening means (86) is arranged to bend the first fastening means (85) at least partially, preferably in the opposite direction to the rear side (88).

7. Process monitoring device according to at least one of the preceding claims, wherein the plant (74) comprises a bioreactor, a plant for chromatographic purification processes, a crossflow plant or the like.

8. Process monitoring device according to at least one of the preceding claims, wherein at least the measuring tube module (4) and the receiving module (16) form a modular Coriolis flowmeter (2).