BIOPROCESS CONTAINER WITH OPTICAL MEASURING DEVICE

Description

[0001] The present invention relates to a bioprocess vessel with an optical measuring device for non-invasive spectroscopic measurement.

[0002] Reusable bioprocess containers, such as bioreactors or mixing tanks, are known from the state of the art. BioreactorsBioreactors are containers in which specially cultivated microorganisms or cells are grown under optimal, controlled conditions in a nutrient medium to obtain either the cells themselves, parts of them, or one of their metabolic products. Specifically, solid (biomass), liquid (nutrient medium), and / or gaseous (e.g., air, oxygen, carbon dioxide, nitrogen) phases can be processed in bioreactors. However, it is essential to ensure optimal conditions in all bioprocessing vessels. For this purpose, various parameters inside the bioreactor are typically measured and monitored using sensors that protrude into the vessel. Possible parameters to be measured include the pH value, the oxygen content, and the temperature of the medium contained within the bioprocessing vessel.If parameters deviate from predefined optimal values, the deviations can be corrected by means of suitable measures.

[0003] One type of sensor for monitoring the medium is an optical sensor or optical measuring device, which measures certain parameters in the medium non-invasively using spectroscopy.

[0004] Before the medium or its individual components can be added to the bioprocess vessel, it is necessary to sterilize the vessel, including any sensors mounted on it, such as the optical sensor mentioned above. This can be done, for example, by autoclaving or steam sterilization. However, such a sterilization process places a high thermal load on the optical sensor, as even slight thermal deformations can affect the alignment of its individual components. Different spectroscopic techniques require different precise setups for optimal spectrum acquisition. Especially in transmission measurements, precise alignment of the excitation radiation and the detection channel is essential.

[0005] Deviations caused by sterilization processes on the optical sensor are often subsequently corrected by statistical treatments of the spectra. However, every correction is prone to error and carries the risk that undesirable deviations will persist even after correction. Furthermore, important information can also be lost during the correction process.

[0006] Additionally, the seals on the optical sensor must be replaced after a certain number of sterilization processes. This replacement requires sending the optical sensor in for service, and after replacing the seals, reinstalling and fine-tuning it in the bioprocess vessel.

[0007] A bioreactor with a window is known from German patent application DE 20 2009 010 255 U1. The bioreactor comprises at least one transparent window, the inside of which is accessible to a medium that can be arranged within the reactor interior. The window has a photocatalytic coating on its inner surface facing the reactor interior, which can be activated from the outer surface facing away from the inside by at least one light source.

[0008] Document WO 2008 / 016411 A1 discloses a port for use with a bioreactor vessel, comprising: i) a base element comprising a hollow tubular section and a base plate configured to be sealed against a hole in the wall of the bioreactor vessel; ii) a hollow, generally tubular socket element for receiving electrical, optical, microfluidic and / or chemical monitoring components, wherein the socket element fits into the bore of the tubular section of the base element, and wherein both the base element and the socket element provide access to the contents of the bioreactor;iii) a monitoring arrangement inserted into the socket element, the arrangement of which includes means for providing incoming optical and / or electrical signals and means for collecting and transmitting measurement signals resulting from the interaction of incoming optical and / or electrical signals with the contents of a bioreactor; and iv) a cover that maintains the position and orientation of components ii) and iii) relative to the base element.

[0009] Furthermore, German patent application DE 10 2015 122 745 B3 discloses a container with a measuring cell housing of an optical measuring cell projecting into its interior. The measuring cell housing has a measuring gap bounded by two opposing side surfaces at a distance from each other and a connecting surface between the side surfaces. Each side surface has an optical window, with at least one optical fiber being able to be positioned in front of the first window and at least one optical fiber being able to be positioned in front of the second window. The measuring cell housing has receiving channels in front of the windows for receiving the at least one optical fiber each. The receiving channels can be subsequently fitted with the optical fibers from the outside. The measuring cell housing with the windows and receiving channels is rigidly connected to the wall of the container's interior.

[0010] The present invention is therefore based on the objective of providing a bioprocess vessel with an optical measuring device for non-invasive spectroscopic measurement, which makes it possible to prevent thermal effects on the optical measuring device through a sterilization process.

[0011] This task is solved by a bioprocess vessel with an optical measuring device for non-invasive spectroscopic measurement, which includes: a container housing suitable for holding at least one fluid to be measured; a port housing connected to the container housing and sealed off from the interior of the container housing; at least one radiation-emitting element designed to transmit electromagnetic radiation through the at least one fluid contained in the container housing; at least one radiation-receiving element designed to receive at least part of the radiation emitted by the radiation-emitting element; and at least one measuring insert holding or supporting the at least one radiation-emitting element and the at least one radiation-receiving element. wherein the measuring insert is at least partially slid into the port housing and is detachably connected to the port housing in the inserted state; wherein the measuring insert has retaining recesses into which the radiation-emitting element and the radiation-receiving element can be inserted, and wherein the measuring insert comprises: at least one retaining surface in which the retaining recesses are formed and which, in the inserted state, is arranged opposite a window, a first deflecting element and / or a second deflecting element, and at least one connecting surface which is connected to the at least one retaining surface and is designed to be connected to the port housing in the inserted state.

[0012] Under a "non-invasive"A measurement method is understood to be a measurement procedure that allows measurements to be taken from outside the bioprocess vessel. It is not necessary for the measuring instruments of the measuring device to penetrate the interior of the bioprocess vessel. The interior of the port housing, which contains the components of the optical measuring device that are sensitive to sterilization, is not connected to the interior of the bioprocess vessel.

[0013] The measuring insert, which holds or supports the at least one radiation-emitting element and the at least one radiation-receiving element, can be easily inserted into and removed from the port housing along with these elements. Thus, the elements sensitive to sterilization are removed from the bioprocess vessel during the sterilization process. Only after the sterilization process is complete is the measuring insert, along with the at least one radiation-emitting element and the at least one radiation-receiving element, inserted into the port housing. When the measuring insert is correctly positioned in the port housing, the radiation-emitting element and the at least one radiation-receiving element are also correctly positioned, enabling an accurate spectroscopic measurement.In particular, the measuring device ensures that the radiation-emitting element and the radiation-receiving element are always precisely aligned with each other. Therefore, a statistical correction of the spectral analysis is no longer necessary.

[0014] The recesses for the radiation-emitting and radiation-receiving elements ensure that, once the measuring insert is placed in the port housing, these elements are always in an optimal position and orientation. In particular, the recesses allow the radiation-emitting and radiation-receiving elements to be inserted into the port housing together or simultaneously, resulting in time and cost savings.

[0015] As "deployed state"The term refers to the state in which the measuring insert is fully inserted into the port housing or has assumed such a position in the port housing that the optical measuring insert is ready for spectroscopic measurement.

[0016] The at least one holding surface is preferably oriented such that it is arranged parallel to a window, a first deflection element and / or a second deflection element.

[0017] The at least one connecting surface is connected to the at least one holding surface and is preferably oriented in such a way that it comes into contact with an inner surface of the port housing at least partially in the inserted state of the measuring insert, in order to be or become detachably connected to the port housing.

[0018] Preferably, the port housing includes at least one window designed to allow electromagnetic radiation to pass at least partially between the interior of the container housing and an interior of the port housing.

[0019] The window preferably represents a window surface that is part of the port housing. The window can be made of a material designed to allow at least partial transmission of electromagnetic radiation. This can occur across the entire electromagnetic spectrum or only across a specific region of the spectrum. The choice of window therefore depends on the desired measurement or the specific spectral range to be analyzed.

[0020] A window may be provided behind which all radiation-emitting and radiation-receiving elements are arranged within the port housing. However, it is also possible for a window to be arranged only in front of individual radiation-emitting and / or radiation-receiving elements.

[0021] The window allows for an optical connection between the interior of the bioprocess vessel and the interior of the port housing, enabling spectroscopic measurements of the medium contained in the bioprocess vessel. However, a fluid connection between the interior of the bioprocess vessel and the interior of the port housing is not required.

[0022] Furthermore, it is preferred that the port housing has at least one measuring gap or measuring recess into which the fluid to be measured can flow from the interior of the container housing.

[0023] The interior of the measuring gap represents a portion of the bioprocess housing's interior, into which some of the medium contained within the housing can flow. The medium contained in the measuring gap can be measured by the optical measuring device using spectroscopy, thus allowing conclusions to be drawn about the total contents of the bioprocess housing.

[0024] Preferably, the measuring gap has at least two opposing windows that are spaced apart from each other in such a way that the measuring gap is formed between the windows.

[0025] In other words, two opposing surfaces of the port housing, which form the measuring slit, are designed, at least in part, as windows, as described above. These two opposing windows allow electromagnetic radiation to be transmitted through the measuring slit during the spectroscopic measurement.

[0026] Preferably, the measuring gap is formed by a radiation deflection device. wherein the radiation deflection device has at least a first deflection element and at least a second deflection element, wherein the first and second deflection elements are arranged opposite each other and are spaced apart from each other at least in certain areas, so that the measuring gap is formed between the first and second deflection elements.

[0027] Alternatively, a radiation deflection device can be connected to the measuring insert and inserted into the port housing together with the measuring insert. wherein the radiation deflection device has at least a first deflection element and at least a second deflection element, wherein the first and second deflection elements are arranged such that they are spaced apart by the at least two windows and the measuring gap.

[0028] In contrast to the embodiment described above, in which the measuring gap is defined by the first and second deflection elements, in this embodiment the measuring gap is formed by at least two opposing windows. The properties of such a window have already been described above. The port housing is thus preferably designed such that the first and second deflection elements can be arranged inside the port housing and are preferably connected to the measuring insert. This allows the first and second deflection elements to be removed from and reinserted from the port housing along with the measuring insert.

[0029] Preferably, the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and then deflect it to the second deflection unit in such a way that the radiation passes through the measuring slit, and wherein the second deflection unit is designed to receive the radiation from the first deflection unit and then deflect it to the radiation-receiving element.

[0030] The first deflecting element receives the electromagnetic radiation from the radiation-emitting element in a first direction and deflects the radiation in a second direction so that it passes through the measuring slit. The first direction is different from the second direction. The second deflecting element receives at least part of the radiation from the first deflecting element and deflects it again so that the radiation is transmitted back to the radiation-receiving element in the first direction. Optionally, a pinhole aperture can be inserted into the beam path. With such a configuration of the radiation-emitting and radiation-receiving elements, a transmission measurement can thus be performed.

[0031] The first and second deflection elements are made of a material that is transparent to electromagnetic radiation; either across the entire electromagnetic spectrum or only for one or more specific spectral ranges.

[0032] The first and second deflection elements are not critical components that can be exposed to thermal stress during a sterilization process without potentially affecting the subsequent measurement results. Therefore, they can remain on the bioprocess vessel during the sterilization process.

[0033] In a preferred embodiment, the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and then deflect it to the measuring slit, wherein a radiation-receiving element is arranged below the measuring slit.

[0034] The radiation-receiving element below the measuring slit is designed to measure the portion of electromagnetic radiation that is emitted to the radiation-receiving element after reacting with or coming into contact with the medium in the measuring slit. Preferably, this is a 90° detection.

[0035] Such a configuration can be a separate embodiment in which the second deflection element is then non-functional. Here, the second deflection element merely limits the measuring gap.

[0036] However, such a configuration can also be used in addition to the transmission measurement described above. This means that multiple radiation-receiving elements are present.

[0037] Preferably, the radiation-emitting element and the radiation-receiving element are arranged at the same position below the measuring slit.

[0038] With the aid of such an arrangement of the radiation-emitting element and the radiation-receiving element, a reflection measurement (e.g., Raman spectroscopy, fluorescence spectroscopy, UV-Vis spectroscopy, or near-infrared spectroscopy) is possible. In other words, electromagnetic radiation is emitted by the radiation-emitting element in the direction of the measuring slit and reflected there by the medium contained in the measuring slit. The radiation-receiving element can measure this reflected portion, being located in the same position as the radiation-emitting element. Preferably, the radiation-emitting element and the radiation-receiving element are designed as a single unit.

[0039] Alternatively, it is also possible for the radiation-emitting element and the radiation-receiving element to be located at the same position below the first deflection element in order to measure the proportion reflected by the medium.

[0040] Furthermore, a surface of the second deflection element, which faces the measuring gap, can be designed to scatter diffusely, at least in some areas. wherein the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and subsequently deflect it to the measuring slit and / or the diffusely scattering surface of the second deflection element, and the radiation-receiving element can be arranged such that it can measure the electromagnetic radiation reflected by the fluid to be measured and / or the diffusely scattering surface.

[0041] With this embodiment, a transflexion measurement (reflection of the electromagnetic radiation at the diffusely scattering surface) and / or a reflection measurement (reflection of the electromagnetic radiation at the medium) is possible.

[0042] Preferably, the radiation-emitting element and the radiation-receiving element are located below the first deflecting element. Similar to the reflection measurement described above, the two elements can also be configured as a single unit. In particular, the radiation-emitting element and the radiation-receiving element are preferably arranged in the same position.

[0043] Preferably, the first and second deflection element are each a prism or each have a radiation-reflecting surface.

[0044] If the first and second deflection elements have a radiation-reflecting surface, then at least part of this surface is coated with a reflective material, such as gold. The surface is oriented in such a way that the electromagnetic radiation can be deflected from the first to the second direction and vice versa. In other words, the reflective surface acts as a deflecting mirror.

[0045] Furthermore, it is preferred that the first and second deflection elements are arranged on at least one window.

[0046] Preferably, at least one window is not completely covered by the first and second deflection elements. For example, a bottom surface of the measuring slit is not covered by the first and second deflection elements. In this case, several measuring methods can be combined within one optical measuring device (see, for example, the reflection measurement or transflexion measurement described above).

[0047] Specifically, a first radiation-emitting element and a first radiation-receiving element could be positioned using the measuring insert in such a way that a transmission measurement could be performed via the first and second deflection elements. Simultaneously, a second radiation-emitting element and a second radiation-receiving element could be positioned below the base of the measuring insert (the area with only the window) in such a way that a reflection measurement (e.g., Raman spectroscopy, fluorescence spectroscopy, UV-Vis spectroscopy, or near-infrared spectroscopy) could be performed in parallel across the base of the measuring slit.

[0048] Preferably, the measuring insert can be clamped into the port housing, locked to the port housing and / or screwed in place.

[0049] These detachable connections between the measuring insert and the port housing allow for easy connection and, prior to sterilization, simple removal of the measuring insert before the sterilization process. Furthermore, the connection type described above ensures a secure bond between the measuring insert and the port housing.

[0050] Preferably, the bioprocess vessel is a bioreactor.

[0051] As a reusable bioreactor, it can be made of materials such as glass or steel. However, it is also conceivable that the bioprocess vessel is a mixing vessel in which no cultivation takes place, but where at least one fluid is mixed, and where it is necessary to monitor the individual state parameters of the fluid. Alternatively, it can be a storage container for at least one fluid. Both the mixing vessel and the storage container are preferably made of glass or steel.

[0052] Preferably, the port housing protrudes at least partially into the interior of the container housing.

[0053] According to a further aspect of the present invention, the present technical problem is solved by an optical measuring device for non-invasive spectroscopic measurement of a bioprocess vessel, which comprises: a port housing which is connectable to a container housing of the bioprocess vessel and is designed such that, in the connected state, it is sealed off from the interior of the container housing; at least one radiation-emitting element which is designed to transmit electromagnetic radiation through at least one fluid contained in the container housing; at least one radiation-receiving element which is designed to receive at least part of the radiation emitted by the radiation-emitting element; and at least one measuring insert which holds or supports the at least one radiation-emitting element and the at least one radiation-receiving element. wherein the measuring insert is at least partially slid into the port housing and is detachably connected to the port housing in the inserted state; wherein the measuring insert has retaining recesses into which the radiation-emitting element and the radiation-receiving element can be inserted, and wherein the measuring insert comprises: at least one retaining surface in which the retaining recesses are formed and which, in the inserted state, can be arranged opposite a window, a first deflecting element and / or a second deflecting element, and at least one connecting surface which is connected to the at least one retaining surface and is designed to be connected to the port housing in the inserted state.

[0054] Preferably, the port housing includes at least one window designed to allow electromagnetic radiation to pass at least partially between the interior of the container housing and an interior of the port housing.

[0055] Furthermore, it is preferred that the port housing has at least one measuring gap or measuring recess into which the fluid to be measured can flow from the interior of the container housing.

[0056] Preferably, the measuring gap has at least two opposing windows that are spaced apart from each other in such a way that the measuring gap is formed between the windows.

[0057] Furthermore, it is preferred that the measuring gap is formed by a radiation deflection device, wherein the radiation deflection device has at least a first deflection element and at least a second deflection element, wherein the first and second deflection elements are arranged opposite each other and are spaced apart from each other at least in certain areas, so that the measuring gap is formed between the first and second deflection elements.

[0058] Preferably, the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and then deflect it to the second deflection unit in such a way that the radiation passes through the measuring slit, and wherein the second deflection unit is designed to receive the radiation from the first deflection unit and then deflect it to the radiation-receiving element.

[0059] Furthermore, it is preferred that the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and then deflect it to the measuring slit, and that a radiation-receiving element is arranged below the measuring slit.

[0060] Preferably, the radiation-emitting element and the radiation-receiving element are arranged at the same position below the measuring slit.

[0061] Preferably, a surface of the second deflection element, which faces the measuring gap, is designed to be diffusely scattering, at least in some areas. wherein the first deflection element is designed to receive electromagnetic radiation emitted by the radiation-emitting element and subsequently deflect it to the measuring slit and / or the diffusely scattering surface of the second deflection element, and wherein the radiation-receiving element is arranged such that it can measure the electromagnetic radiation reflected by the fluid to be measured and / or the diffusely scattering surface

[0062] Preferably, the first and second deflection element each have a prism or a radiation-reflecting surface.

[0063] It is preferred that the first and second deflection elements are arranged on at least one window.

[0064] Furthermore, it is preferred that the measuring insert can be clamped into the port housing, locked to the port housing and / or screwed in place.

[0065] Preferably, the port housing, when connected, protrudes at least partially into the interior of the container housing.

[0066] These and other objectives, features, and advantages of the present invention will become clearer upon study of the following detailed description of preferred embodiments and the accompanying drawings. It should also be noted that, although embodiments are described separately, individual features of these embodiments can be combined to form additional embodiments. Figure 1a) shows a top view of a partial area of ​​a container housing of a bioprocess vessel with an optical measuring device according to a first embodiment; Figure 1b) shows a sectional view along the section axis BB in Figure 1a); Figure 2a) shows a top view of a partial area of ​​a container housing of a bioprocess vessel with an optical measuring device according to a second embodiment; Figure 2b) shows a sectional view along the section axis AA in Figure 2a ); Figure 3a) shows a top view of a partial area of ​​a container housing of a bioprocess vessel with an optical measuring device according to a third embodiment; Figure 3b) shows a sectional view along the section axis BB in Figure 3a Figure 4 shows Figure 1b ) with the path of the electromagnetic radiation shown; Figure 5 shows Figure 2b ) with the path of the electromagnetic radiation shown; Figure 6 shows Figure 3b) with the electromagnetic radiation path shown; Figure 7 shows a sectional view through part of a bioprocess vessel with an optical measuring device with 90° detection; and Figure 8 shows a sectional view through part of a bioprocess vessel with an optical measuring device with transflexion measurement.

[0067] Figures 1a) and 1b ) Figure 1 shows a first embodiment of an optical measuring device 100, which is inserted into a bioprocess vessel 10. The bioprocess vessel 10 is preferably a bioreactor, a mixing vessel, or a storage tank, preferably made of steel or glass. The bioprocess vessel 10 is designed to hold at least one fluid that is to be measured or monitored by the optical measuring device 100.

[0068] To insert or connect the optical measuring device 100 to the bioprocess vessel 10, the vessel housing 12 has a cutout 14. The shape and size of the cutout 14 are designed such that the optical measuring device 100 can be inserted from an outer surface 16 of the vessel housing 12 towards an interior space 18 of the vessel housing 12. Preferably, the cutout 14 is circular. In particular, it is preferred that the optical measuring device 100 can be inserted into the bioprocess vessel 10 such that it projects at least partially into the interior space 18 of the bioprocess vessel 10.

[0069] The optical measuring device 100 comprises a port housing 102, which can accommodate optical measuring instruments and whose interior 104 is designed to be fluid-tight from the interior 18 of the container housing 12. The container housing 12 preferably has a container housing projection 20, which projects from a lateral surface 22 of the container housing 12 along the container housing cutout 14 towards the interior 18 of the container housing 12. Preferably, the container housing projection 20 projects perpendicularly from the lateral surface 22 of the container housing 12. The port housing 102 also has a lateral surface 106 and, in the installed state, overlaps at least partially with the container housing projection 20. As shown in Figure 1b ) shown, which is a sectional view along the section axis BB from Figure 1aAs shown in the figure, the outer surface 106 of the port housing 102 can project over the container housing projection 20 into the interior 18 of the container housing 12. To ensure that the bioprocess vessel 10 is fluid-tight and that no fluid can escape through the container housing opening 14, it is advantageous to arrange at least one sealing ring 24 between the container housing projection 20 and the outer surface 106 of the port housing 102.

[0070] At a front end 108 of the port housing 102, which projects into the interior 104 of the port housing 102, at least one window 110 can be formed, at least partially. The window 110 can be made of glass or plastic and be transparent to electromagnetic radiation across the entire spectrum or only across individual spectral ranges. The window 110 allows optical measuring instruments non-invasive access to the interior 18 of the container housing 12, while the interior 104 of the port housing 102 remains fluid-tight from the interior 18 of the container housing 12.

[0071] As in Figure 1b ) shown, the window 110 extends over the entire front end 108 of the port housing 102.

[0072] To enable transmission measurement, the optical measuring device 100 preferably has a measuring gap 112. The measuring gap 112 is preferably formed by two prisms 114 (deflection elements). The prisms 114 are arranged on the window 110 and are spaced apart from each other such that the desired measuring gap 112 is formed between the prisms 114. The measuring gap 112 is in fluid communication with the interior 18 of the container housing 12, so that a portion of the fluid from the container housing 12 can flow into the measuring gap 112 and be measured there as a reference quantity for the remaining contents of the container housing 12. As described in Figure 1bAs shown in the figure, the prisms 114 preferably have a triangular shape in a sectional view. Preferably, this is a right-angled triangle. The surface 118 of the prism 114, which is opposite the surface that defines the measuring slit 112, is arranged obliquely opposite an axis of rotation R of the port housing 102.

[0073] Alternatively, the measuring gap 112 can also be formed by transparent elements (not shown here) that have a similar shape to the prisms 114. The transparent elements can have material properties like the window 110. In contrast to the prisms 114, however, the transparent elements have a reflective coating, at least in some areas, on the inclined surface 118 (diagonally opposite the axis of rotation R of the port housing 102).

[0074] Although Figure 1bIf a window 110 is shown that closes the port housing 102 at the front end 108, the prisms 114 or the transparent elements can also directly close the front end 108 of the port housing 102. A bottom surface 120 of the measuring gap 112 can then be designed as a window 110 or be opaque, similar to the lateral surface 104 of the port housing 102.

[0075] A rear end 116 of the port housing 102 is preferably open to the outside of the port housing 102. Through this open rear end 116, at least one measuring insert 122 can be inserted at least partially into the interior 104 of the port housing 102. Figure 1b Figure 1 shows the measuring insert 122 in its installed state. The measuring insert 122 is detachably connected to the port housing 102, so that the measuring insert 122 can be easily removed from the port housing 102 during a sterilization process and subsequently reinserted into the port housing 102.

[0076] The measurement deployment from Figure 1 It is advantageously suited for transmission measurement. In particular, the measuring insert 122 is designed such that it can hold or support at least one radiation-emitting element 124 and at least one radiation-receiving element 126. Figure 1bFigure 1 shows an embodiment with a measuring insert 122 that holds a radiation-emitting element 124 and a radiation-receiving element 126. The radiation-emitting element 124 is designed to emit electromagnetic radiation, while the radiation-receiving element 126 is designed to receive electromagnetic radiation. The radiation-emitting element 124 preferably has at least one light guide 127. At least one radiation element (not shown here), such as at least one LED, can emit electromagnetic radiation via the at least one light guide 127 through the radiation-emitting element 124. Preferably, the radiation-emitting element 124 has a radiation output coupling element 128 at a front end. The electromagnetic radiation can exit or be coupled out of the radiation-emitting element 124 via the radiation output coupling element 128.The radiation-emitting element 124 is preferably arranged with the aid of the measuring insert 122 such that the electromagnetic radiation can be emitted or coupled out parallel to the axis of rotation R of the port housing 102 and sent to a first prism 114a (first deflection element). The electromagnetic radiation striking the first prism 114a is deflected by the first prism 114a such that the electromagnetic radiation shines through the measuring slit 112 and at least partially strikes the second prism 114b (second deflection element). The electromagnetic radiation is at least partially absorbed and / or reflected in the measuring slit 112 by the medium contained therein. Thus, only a portion of the emitted electromagnetic radiation reaches the second prism 114b.The second prism 114b, in turn, deflects the electromagnetic radiation such that the electromagnetic radiation is sent to the radiation-receiving element 126. The radiation-receiving element 126 preferably comprises a radiation coupling element 130, via which the received radiation can be coupled. At least one optical fiber 127 guides the received radiation to a photodetector (not shown here), which is suitable for receiving and evaluating the received radiation. Preferably, the radiation-receiving element 126 is arranged in the port housing 102 by the measuring insert 122 such that the electromagnetic radiation can radiate from the second prism 114b to the radiation-receiving element 126 parallel to the axis of rotation R of the port housing 102. Figure 4 shows Figure 1b ) with the path of the electromagnetic radiation shown.

[0077] The measuring insert 122 has at least one retaining surface 132, which, in the inserted state, is preferably oriented perpendicular to the axis of rotation R of the port housing 102. The retaining surface 132 has retaining recesses 134 into which a radiation-emitting element 124 or a radiation-receiving element 126 can be inserted. The aforementioned elements 124, 126 can be screwed into the retaining recess 134 or held in the retaining recess 134 by an interference fit. As in Figure 1b ) shown, preferably the radiation coupling element 128 and the radiation coupling element 130 are held by the measuring insert 122.

[0078] Furthermore, the measuring insert 122 has at least one connecting surface 136. The connecting surface 136 preferably extends from the holding surface 132 at least partially parallel to the axis of rotation R of the port housing 102 and, in the inserted state of the measuring insert 122, is in contact at least partially with the outer surface 106 of the port housing 102. The connecting surface 136 is detachably connected to the outer surface 106 of the port housing 102, so that the measuring insert 122 can be easily removed from the port housing 102 during sterilization. The connecting surface 136 can, for example, have at least one rubber ring (not shown here) that establishes a stable connection between the measuring insert 122 and the port housing 102. Alternatively or additionally, the measuring insert can be screwed into the port housing 102. A rear end 138 of the connecting surface 136 is designed as a free end and can be, as shown in Figure 1b) shown, be angled relative to the remaining connecting surface 136. Preferably, the rear end 138 of the connecting surface 136 extends perpendicular to the axis of rotation R of the port housing 102. This rear end 138 can be used to prevent the measuring insert from being inserted too deeply into the port housing 102.

[0079] The connecting surface 136 of the measuring insert 122 could also be designed, in the uninserted state, such that the connecting surface 136 widens from the retaining surface 132 to the rear end 138 of the connecting surface 136. This allows the measuring insert 122 to form a kind of clamp, which, by compressing the rear end 138 of the connecting surfaces 136, enables the measuring insert 122 to be inserted into the port housing 102. The measuring insert 122 is thus clamped into the port housing 102.

[0080] The measuring insert 122 is preferably made of metal or plastic.

[0081] The Figures 2a) and 2b ) Figure 1 shows a second embodiment of an optical measuring device 100. However, only those parts of the optical measuring device 100 that differ from the first embodiment are described below. The description of the remaining parts of the optical measuring device 100 applies accordingly to the second embodiment.

[0082] The optical measuring device 100 from the Figures 2a) and 2b ) is suitable, unlike the optical measuring device 100 from the Figures 1a) and 1b) for reflection measurement (e.g., Raman spectroscopy). For this purpose, electromagnetic radiation is emitted by the radiation-emitting element 124, preferably parallel to the rotation axis R of the port housing 102. The electromagnetic radiation is then reflected and / or absorbed by the medium located in the bioprocess vessel 10. However, only the portion of the electromagnetic radiation reflected by the medium is measured. For this purpose, the radiation-receiving element 126 is preferably located at the same position as the radiation-emitting element 124. In other words, the radiation-receiving element 126 receives radiation, which is preferably reflected parallel to the rotation axis R of the port housing 102 from the medium to the radiation-receiving element 126. It is not absolutely necessary for the optical measuring device 100 to have a measuring slit 112. As in the Figures 2a) and 2bAs shown in Figure 1, a measuring slit 112 may be provided. The radiation-emitting element 124 and the radiation-receiving element 126 are preferably arranged in the inserted state of the measuring insert 122 such that the electromagnetic radiation can radiate through the base surface 120 of the measuring slit 112. It is crucial that the base surface 120 is designed as a window 110, at least in part. If the optical measuring device 100 does not have a measuring slit 112, the radiation-emitting element 124 and the radiation-receiving element 126 can be positioned differently compared to Figure 1. Figure 2 They can also be arranged parallel to the rotation axis R of the port housing 102. The only crucial point here is that the aforementioned elements are arranged below a window 110. Figure 5 shows Figure 2b ) with the path of the electromagnetic radiation shown.

[0083] Preferably, the radiation extraction element 128 and the radiation coupling element 130 are combined, as shown in Figure 2b ) shown. The optical fibers 127 of the radiation-emitting element 124 and the radiation-receiving element 126 are preferably bundled into a fiber bundle.

[0084] To calibrate the radiation-receiving element 126 for reflection measurement, particularly for calibrating the photodetector, a further radiation-emitting element (not shown here) can be arranged in the measuring insert 122 parallel to the direction of rotation R of the port housing 102 or laterally offset from the radiation-receiving element 126. In this case, the measuring gap 112 is limited by at least one deflecting element, below which the further radiation-emitting element is arranged. The measuring gap 112 can also be formed, for example, by two deflecting elements, as shown in Figure 1shown. Alternatively, the second deflection element can also be replaced by a boundary element without a deflection function.

[0085] The Figures 3a) and 3b ) A third embodiment of an optical measuring device 100 is shown. Here, various measuring methods are combined in a simple manner in an optical measuring device 100 with the help of the measuring insert 122.

[0086] Specifically, in the third embodiment, the following can be considered: Figure 1 The described transmission measurement is performed. In addition, a further radiation-receiving unit 126 is located below the measuring gap 112, which is designed to receive electromagnetic radiation that is deflected or deflected by the medium in the measuring gap 112 or emitted after contact with the medium. Preferably, this is a 90° detection unit. Figure 6 shows Figure 3b) with the path of the electromagnetic radiation shown.

[0087] Regarding the embodiment from Figure 3 It is also conceivable that at least one radiation-receiving element 126 is arranged below the measuring slit 112. This means that no transmission measurement is performed, but only the proportion of electromagnetic radiation emitted after contact with the medium to the radiation-receiving element 126 below the measuring slit 112 is detected and measured. Figure 7 Figure 1 shows a cross-sectional view through part of a bioprocess vessel 10 with an optical measuring device 100, in which the path of the electromagnetic radiation for 90° detection is shown. As can be seen from the drawing, the second deflecting element here only limits the measuring gap 112. The electromagnetic radiation is not deflected.

[0088] Furthermore, the in Figure 3The arrangement shown can also be advantageously used for transflexion measurement. For this purpose, the surface of the second prism 114b or the second deflection element, which faces the measuring slit 112, is designed, at least in part, as a diffusely scattering surface 140. At least a portion of the electromagnetic radiation passing through the measuring slit 112 is reflected by this diffusely scattering surface 140 and can subsequently be received or detected by a radiation-receiving element 126 located below the first prism 114a. Figure 8 Figure 1 shows a cross-sectional view through part of a bioprocess vessel 10 with an optical measuring device 100, in which the course of the electromagnetic radiation is shown for a transflexion measurement.

[0089] In both the first and third embodiments, the measuring gap 112 is formed by the prisms 114, which come into contact with the medium in the container housing 12. The prisms 114 remain in the bioprocess container 10 during the sterilization process, while the measuring insert 122 is removed from the port housing 102. However, it is also conceivable that the prisms 114 or the transparent elements are arranged in the interior 104 of the port housing 102 and are preferably connected to the measuring insert 122. Thus, the prisms 114 or the transparent elements can also be removed from the port housing 102 during the sterilization process. The prisms 114 or the transparent elements could be attached to the measuring insert 122 by means of spacers.

[0090] To form a measuring gap 112, the front end 108 of the port housing 102 could have a measuring gap 112. Specifically, the front end 108 of the port housing 102 could have a first projection and a second projection, into each of which a prism 114 or a transparent element projects. The surfaces of the projections, which are opposite each other and define the measuring gap 112, are at least partially designed as windows 110.

[0091] Although the transparent elements and the prisms 114 in the illustrated embodiments consist of two parts, these deflection elements could also be made from a single, specially manufactured piece that, for example, allows a laterally shifted 180° reflection. In this case, the measuring insert 122 could be directly oriented by structures in the deflection elements (e.g., by pins or grooves).

[0092] In the embodiments described above, window 110 is described as a transparent element that is transparent to electromagnetic radiation. However, it is also conceivable that window 110 is a more complex optical element, suitable, for example, for microscopy.

[0093] Embodiment 2 shows an embodiment in which several measurement techniques are combined in an optical measuring device. It is also possible to combine 127 different measurement techniques depending on the type of optical fiber used. Reference symbol list

[0094] 10 Bioprocess vessel 12 Vessel housing 14 Vessel housing cutout 16 Outside of the vessel housing 18 Inside of the vessel housing 20 Vessel housing projection 22 Shell surface of the vessel housing 24 Sealing ring 100 Optical measuring device 102 Port housing 104 Interior of the port housing 106 Outer surface of the port housing 108 Front end of the port housing 110 Window 112 Measuring slit 114 Prism 114a First prism 114b Second prism 116 Rear end of the port housing 118 Slanted surface 120 Bottom surface of the measuring slit 122 Measuring insert 124 Radiation emitting element 126 Radiation receiving element 127 Optical fiber 128 Radiation coupling element 130 Radiation coupling element 132 Mounting surface 134 Mounting recess 136 Connecting surface 138 Rear end of the connecting surface 140 Diffuse scattering surface Rotation axis of the port housing

Claims

1. Bioprocess container (10) with an optical measurement device (100) for non-invasive spectroscopic measurement comprising: • a container housing (12), which is suitable for receiving at least one fluid to be measured; • a port housing (102), which is connected to the container housing (12) and is closed off from the interior space (18) of the container housing (12); • at least one radiation emitting element (124), which is designed to send electromagnetic radiation through at least one fluid contained in the container housing (12); • at least one radiation receiving element (126), which is designed to at least partially receive the radiation which was emitted by the radiation emitting element (124); and • at least one measurement insert (122), which supports and / or holds at least one radiation emitting element (124) and at least one radiation receiving element (126), wherein the measurement insert (122) is at least partially insertable into the port housing (102) and is releasably connected to the port housing (102) in the inserted state; wherein the measurement insert (122) has retaining recesses (134), into which the radiation emitting element (124) and the radiation receiving element (126) are insertable, and wherein the measurement insert (122) comprises: • at least one retaining surface (132), in which the retaining recesses (134) are formed and which, in the state inserted into the port housing (102), is arranged opposite a window (110), a first deflecting element and / or a second deflecting element, and • at least one connecting surface (136), which is connected to at least one retaining surface (132) and is designed to be connected to the port housing (102) in the inserted state.

2. Bioprocess container (10) according to claim 1, wherein the port housing (102) comprises at least one window (110), which is designed to at least partially allow electromagnetic radiation to pass between the interior space (18) of the container housing (12) and an interior space (104) of the port housing (102).

3. Bioprocess container (10) according to claim 1 or 2, wherein the port housing (102) has at least one measurement gap (112) or respectively a measurement recess, into which or respectively into which the fluid to be measured flows from the interior space (18) of the container housing (12).

4. Bioprocess container (10) according to claim 3, wherein the measurement gap (112) has at least two opposing windows (110), which are spaced apart from one another such that the measurement gap (112) is formed between the windows (110).

5. Bioprocess container (10) according to claim 3, wherein the measurement gap (112) is formed by a radiation deflecting device, wherein the radiation deflecting device comprises at least a first deflecting element and at least a second deflecting element, wherein the first and the second deflecting element are arranged opposite one another and are at least partially spaced apart from one another, so that the measurement gap (112) is formed between the first and the second deflecting element.

6. Bioprocess container (10) according to claim 4, wherein a radiation deflecting device is connected to the measurement insert (122) and is insertable together with the measurement insert (122) into the port housing (102), wherein the radiation deflecting device comprises at least a first deflecting element and at least a second deflecting element, wherein the first and the second deflecting element are arranged such that they, through at least two windows (110), delimit the measurement gap (112) being spaced apart from one another.

7. Bioprocess container (10) according to claim 5 or 6, wherein the first deflecting element is designed to receive electromagnetic radiation, which is emitted by the radiation emitting element (124), and to subsequently deflect it to the second deflecting unit such that the radiation passes through the measurement gap (112), and wherein the second deflecting unit is designed to receive the radiation from the first deflecting unit and to deflect it to the radiation receiving element (126).

8. Bioprocess container (10) according to one of claims 5 to 7, wherein the first deflecting element is designed to receive electromagnetic radiation, which is emitted by the radiation emitting element (124), and to subsequently deflect it to the measurement gap (112), and wherein a radiation receiving element (126) is arranged below the measurement gap (112).

9. Bioprocess container (10) according to one of claims 1 to 6, wherein the radiation emitting element (124) and the radiation receiving element (126) are arranged at the same position below the measurement gap (112).

10. Bioprocess container (10) according to claim 5 or 6, wherein a surface (140) of the second deflecting element, which faces the measurement gap (112), is formed at least partially as a diffusely scattering surface, wherein the first deflecting element is designed to receive electromagnetic radiation, which is emitted by the radiation emitting element (124), and to deflect it to the measurement gap (112) and / or to the diffusely scattering surface (140) of the second deflecting element, and wherein the radiation receiving element (126) is arranged such that it can measure the electromagnetic radiation, which is reflected by the fluid to be measured and / or by the diffusely scattering surface (140).

11. Bioprocess container (10) according to one of claims 5 to 10, wherein the first and the second deflecting element are each a prism (114) or each have a radiation reflecting surface.

12. Bioprocess container (10) according to one of claims 5 or 7 to 11, wherein the first and the second deflecting element are arranged on at least one window (110).

13. Bioprocess container (10) according to one of the preceding claims, wherein the measurement insert (122) is clampable into the port housing (102), engageable with the port housing (102) and / or screwable.

14. Bioprocess container (10) according to one of the preceding claims, wherein the bioprocess container is a bioreactor; and / or wherein the port housing (102) at least partially protrudes into the interior space (18) of the container housing (12).

15. Optical measurement device (100) for non-invasive spectroscopic measurement for a bioprocess container (10) comprising: • a port housing (102), which is connectable to a container housing (12) of the bioprocess container (10) and is formed such that it, in the connected state, is closed off from the interior space (18) of the container housing (12); • at least one radiation emitting element (124), which is designed to send electromagnetic radiation through at least one fluid contained in the container housing (12); • at least one radiation receiving element (126), which is designed to at least partially receive the radiation which was emitted by the radiation emitting element (124); and • at least one measurement insert (122), which supports and / or holds at least one radiation emitting element (124) and at least one radiation receiving element (126), wherein the measurement insert (122) is at least partially insertable into the port housing (102) and is releasably connected to the port housing (102) in the inserted state; wherein the measurement insert (122) has retaining recesses (134), into which the radiation emitting element (124) and the radiation receiving element (126) are insertable, and wherein the measurement insert (122) comprises: • at least one retaining surface (132), in which the retaining recesses (134) are formed and which, in the state inserted into the port housing (102), is arranged opposite a window (110), a first deflecting element and / or a second deflecting element, and • at least one connecting surface (136), which is connected to at least one retaining surface (132) and is designed to be connected to the port housing (102) in the inserted state.