Multi-sensor components for bioprocess control

Abstract

To provide: a multi-sensor component for installation of sensors at an individual port of a container for culturing biological material; a system comprising a sensor receiver and a multi-sensor component; a container comprising a port, the multi-sensor component and the sensor-receiver; a luminophore unit for attachment to the multi-sensor component; and a method of producing the multi-sensor component.SOLUTION: A housing of the multi-sensor component can be introduced by a front housing segment into a receiving opening extending through an individual port of the container, so that the front housing segment faces the inside of the container. The multi-sensor component has a first sensor unit or a mount for a first sensor unit arranged on the housing segment, and has a second sensor unit or a mount for a second sensor unit arranged on the housing segment.SELECTED DRAWING: Figure 10

Description

Technical Field

[0001] The present invention relates to containers for culturing biological substances, in particular to process control during production processes in bioreactors and shake flasks.

Background Art

[0002] Bioreactors and shake flasks are used for culturing microorganisms, animal cells and plant cells, thereby opening up a wide range of application areas for biotechnological production processes. Generally, it is desirable to further optimize such processes. In particular, for the production of biopharmaceuticals, improvement of production yield and thus increase in profit are targeted. Various approaches have been provided for the control and regulation of production processes, the increase of production yield and cost reduction.

[0003] On the one hand, the control and regulation of the process can be carried out by determining the substrate concentration and the product concentration. However, this takes time and usually requires offline analysis that consumes a large amount of resources. Due to sample dilution, this is further associated with a non-negligible risk of contamination.

[0004] On the other hand, the control of the process and thus the yield can be optimized by performing real-time process control of important parameters. For increasing the production yield, in particular, on-site monitoring of parameters such as temperature, metabolites or substances related to product formation is as advantageous as the adjustment of culture conditions in real time.

[0005] For real-time parameter control, a biosensor can be used. This type of biosensor can be installed, in particular, at the ports of a bioreactor, a shaking flask, or generally any disposable or reusable container for culturing biological materials. This is because such ports form an opening on the inside of the container. The ports of bioreactors or shaking flasks often correspond to specific standards, such as Ingold ports or Broadly-James ports.

[0006] Sometimes, it is also desirable to monitor a plurality of important parameters. For this purpose, another biosensor can be installed at another port of the container. Furthermore, it may be desirable to monitor the parameters by spectroscopy, where the quenching of a fluorophore is detected.

[0007] However, the drawback of monitoring a plurality of parameters in parallel can be an increasing risk of contamination. Furthermore, especially in the case of small containers or shaking flasks, the number of available ports can be limited. Summary of the Invention Problems to be Solved by the Invention

[0008] Therefore, the problem of the present invention is to enable real-time parameter control of a plurality of parameters while reducing the risk of contamination and / or to monitor a plurality of parameters even in the case of a container having a small number of available ports. Means for Solving the Problems

[0009] The above problems are solved by the constituent elements of the independent claims. Advantageous developments of the present invention are defined in the dependent claims.

[0010] The present invention provides a multi-sensor component for installing at least two sensors at individual ports of a container for culturing biological materials, in particular a bioreactor or a shaking flask.

[0011] The multi-sensor component of the present invention includes a housing, which can be inserted into a receiving opening extending through a port of a container by at least a front housing portion, whereby the front housing portion is directed towards the inside of the container.

[0012] The receiving opening extending through the port of the container may be formed, for example, by the port itself, i.e., it may be a through-opening in the container wall formed through the port. This through-opening connects the inside of the container to the outside of the container. In other words, the multi-sensor component of the present invention may be directly insertable into the port.

[0013] However, in an advantageous embodiment, the receiving opening extending through the port of the container is an intermediate element that can be placed within the port, in particular an opening within a sensor housing, as will be described in more detail hereinafter. In such a case, the multi-sensor component of the present invention may be, for example, directly insertable into the intermediate section or the sensor housing, and thus indirectly insertable into the port.

[0014] The housing of the multi-sensor component is configured as follows in an advantageous embodiment. That is, it is configured to be completely insertable into the receiving opening extending through the port of the container. That is, in the state of use, it is particularly completely surrounded by the port or the sensor housing, especially in the radial direction. Therefore, the housing of the multi-sensor component can have a constant outer shape, particularly along the longitudinal axis of the multi-sensor component. That is, it may be configured, in particular, in a cylindrical shape along the entire length of the multi-sensor component.

[0015] The housing of the multi-sensor component of the present invention has, in the housing portion in front of itself, a first sensor unit or at least one holding portion for the first sensor unit. Further, in the front housing portion, a second sensor unit or at least one holding portion for the second sensor unit is also arranged.

[0016] Therefore, when the multi-sensor component is inserted into the receiving opening extending through the port of the container, the sensor unit is preferably arranged in the front housing portion, that is, directed towards the inside of the container, and in particular, is present inside the container. Further, when the multi-sensor component is inserted into the receiving opening extending through the port of the container, the holding portion for the sensor unit is preferably arranged in the front housing portion, that is, directed towards the inside of the container, and in particular, is present inside the container. Further, the holding portion for the sensor unit is preferably configured to hold the sensor unit as follows. That is, when the multi-sensor component is inserted into the receiving opening extending through the port of the container, it is directed towards the inside of the container, and in particular, is configured to be present inside the container.

[0017] Therefore, for example, two, particularly different, sensor units may be arranged in the front housing portion. However, the first sensor unit and the holding portion for the second, particularly different, sensor unit may also be arranged in the front housing portion. Two holding portions may be provided, that is, the holding portion for the first sensor unit and the holding portion for the second, particularly different, sensor unit may be provided. Naturally, even more sensor units and / or holding portions for the sensor units may be provided.

[0018] A multi-sensor component including at least two sensor units or holding parts for sensor units can advantageously combine two or more sensors at one port. This is advantageous, for example, in the case of an oscillating flask when the available ports are limited. In particular, this enables the need-oriented use of non-sterilizable sensors combined at one port. Generally, the present invention relates to multi-use applications (glass bioreactor or stainless steel bioreactor), single-use applications (so-called disposable bioreactors or bags), and also to shaking incubators (shaking flasks and cell culture flasks).

[0019] Advantageously, at least one sensor unit is configured as a biosensor unit, in particular for measuring sample-specific parameters. In other words, one sensor unit, a plurality of sensor units, or one of a plurality of sensor units may be configured as a biosensor unit. The biosensor unit advantageously includes a bioreceptor and is configured in particular to convert a biological signal into a physicochemical signal via the bioreceptor. For example, the biosensor unit may be configured to determine the concentration of a saccharide or a protein.

[0020] If one or two holding parts for the first sensor unit and / or the second sensor unit are provided, alternatively at least one of the holding parts is configured for holding a biosensor unit as described above. Of course, both holding parts may be correspondingly configured. Furthermore, in some cases, both may be provided cumulatively. For example, the first sensor unit is configured as a biosensor unit as described above, and the holding part for the second sensor unit is configured for holding a sensor unit configured as a biosensor unit as described above.

[0021] The biosensor unit may be configured, for example, in the form of a flat chip and advantageously as a modular unit, and / or the corresponding holder may be configured for holding this type of unit.

[0022] Furthermore, advantageously, at least one sensor unit, in particular this type of sensor unit not configured as a biosensor unit, is configured as a lumophore unit for luminescence-based parameter measurement. In other words, one sensor unit, a plurality of sensor units or one of a plurality of sensor units may be configured as a lumophore unit.

[0023] If one or two holders are provided for the first sensor unit and / or the second sensor unit, alternatively at least one of the holders is configured for holding a lumophore unit as described above. Of course, both holders may be correspondingly configured. Furthermore, in some cases, both may be provided cumulatively. For example, the first sensor unit is configured as a lumophore unit as described above, and the holder for the second sensor unit is configured for holding a sensor unit configured as a lumophore unit as described above.

[0024] Particularly advantageously, the first sensor unit may be configured as a biosensor unit, or the corresponding holder may be configured for holding a biosensor unit, the second sensor unit may be configured as a lumophore unit, or the corresponding holder may be configured for holding a lumophore unit.

[0025] In other words, the present invention particularly enables the combined use of a lumophore and a biosensor, where the lumophore unit and the biosensor unit are integrated within the housing. Thus, the present invention relates to a "multi-sensor unit", for example, for the production of biopharmaceuticals. This enables the evaluation of multiple parameters to be measured at one port (via the lumophore and the biosensor).

[0026] The sensor unit may be configured as an alternating field unit for dielectric-based parameter measurement. Further, the sensor unit may be configured as a transistor unit for field effect-based parameter measurement. Further, a holding part for the above-described sensor unit may also be provided.

[0027] The sensor unit or the corresponding holding part may have at least one dimension extending perpendicular to the longitudinal direction of the multi-sensor component. This dimension is greater than 35%, preferably 50%, particularly preferably 65% of the thickness of the multi-sensor component perpendicular to its longitudinal direction. Advantageously, the biosensor unit or the holding part for the biosensor unit may have this kind of dimension. Further, advantageously, the lumophore unit or the holding part for the lumophore unit may have this kind of dimension. The alternating field or the transistor unit or the holding part for this kind of unit may also have this kind of dimension.

[0028] The measurement of the sample-specific parameters by the biosensor unit can imply a specific measured quantity, i.e., that the sample is selectively detected, i.e., in particular, that multiple parameters, for example, various samples, are not detected together at the same time.

[0029] During the luminescence-based parameter measurement by the lumophore unit, signal quenching related to the sample can be performed. The excitation wavelength may be wavelength-shifted and / or phase-shifted by interaction with the measured quantity.

[0030] When a charge moves in a specimen in an electric field, dipoles are induced. During dielectric-based measurements by an alternating field unit, in the sensor unit, interactions related to the frequency can be utilized.

[0031] During the measurement of electric field effect-based parameters by a transistor unit, an ionic specimen can generate mirror charges that cause conductivity in a semiconductor element. This is done especially when it adheres reversibly and ion-selectively to the sensor chip.

[0032] A sensor unit configured as a lumophore unit preferably includes a substrate that has accommodation means for accommodating the lumophore substance, where the accommodation means is configured in particular as a cavity in the substrate. Naturally, in the case of one or two holding parts as well, corresponding holding parts may be configured for holding this type of substrate.

[0033] The substrate of the lumophore unit may have a front substrate region and a rear substrate region such that the front substrate region is directed towards the inside of the container and the rear substrate region is directed towards the outside of the container. This is the case when the lumophore unit is inserted into a port or an accommodation opening extending through the port of the container and / or when a multi-sensor component or the front housing part thereof is inserted into a port or an accommodation opening extending through the port of the container.

[0034] Here, the front substrate region may include at least one accommodation means configured in particular as a cavity. Alternatively or additionally, the rear substrate region may include at least one light guide and preferably a light source (laser, LED, VCSEL (Vertical-Cavity Surface-Emitting Lasers)) and / or a photodiode, whereby the light of the light source is guided to the accommodation means and / or the light is guided from the accommodation means to the photodiode.

[0035] The front substrate region may be composed of a material containing glass, in particular glass or glass ceramics, or may contain a material of this kind, where accommodation means are introduced as cavities into this material using laser cutting.

[0036] The rear substrate region may contain an optical fiber or may be composed of an optical fiber, and advantageously serves to guide light to accommodation means configured as cavities, where this optical fiber advantageously at least partially forms the light guide described above.

[0037] In an advantageous embodiment, the front substrate region, in particular containing glass, is configured in the shape of a disk, and / or the rear substrate region, advantageously containing an optical fiber, is configured in the shape of a rod. Furthermore, the front substrate region may be connected to the rear substrate region by laser welding.

[0038] Thus, the basic structure of the lumophore unit may be a fiber rod, where a cavity may be provided at the end of this fiber rod facing the medium or in contact with the medium. A cavity of this kind may be manufacturable as described above, which is done by cutting out a segment corresponding to a glass disk by means of a laser and then forming a material bond with the fiber rod via laser welding.

[0039] The glass fibers aligned on each lumophore cavity of the fiber rod can be excited via LED light or laser light. In relation to the concentration of the analyte, the quenching rate of the excited state may be guided from the lumophore to the detector cell via the corresponding glass fiber. Here, for example, a photodiode integrated in the housing may be provided. By using one or more light guides, it may be possible to compensate for the limitations in the location during light extraction and light input.

[0040] Basically, the lumophore unit is configured to accommodate or store the lumophore substance. However, in another embodiment, such a substance may already be included. Thus, the lumophore unit may contain the lumophore substance, where this substance is advantageously stored by the receiving means of the substrate configured as a cavity. This substance may be fixed by heat in contact with the receiving means, for example a cavity, or within the receiving means, for example a cavity.

[0041] The receiving means or cavity may be configured to accommodate a liquid or gel-like lumophore substance, or this type of substance may already be included. Thus, the lumophore substance may in particular be configured as a soft mass (i.e., in particular softer than the substrate and / or the front substrate region). In particular, if there are a plurality of cavities, the lumophores may be individually filled into the cavities. This enables the combination of optimal parameters (pH, pO 2 2, pCO 2 2, temperature, concentrated saccharides, proteins, etc., where the saccharides and proteins can advantageously be determined by the biosensor unit) in the selected measurement region, at the port of a bioreactor, a shaking flask or another container provided with a port.

[0042] Thus, advantageously, a plurality of receiving means may be provided within the substrate or within the front substrate region. Here, these may each be configured as a cavity. Thus, advantageously, it is also possible to use a plurality of, in particular different, lumophore substances.

[0043] The lumophore substance or lumophore particularly includes graphene quantum dots (GQDs), heterocyclic GQDs (e.g., N-GQDs) and / or metal-organic compounds. In particular, the following are conceivable. · DHFAE: 2,7'-Dihexyl-5(6)-octadecyl-carboxamidofluorescein ethyl ester and phosphorescent ruthenium(II)-tris-4,7-diphenyl-1,10-phenanthroline as an inert reference standard Fluorescent dye sensitive to pH in the pH range of 7.3 to 9.3 · HPTS: 8-Hydroxypyrene-1,3,6-trisulfonic acid as the trisodium salt Fluorescent dye sensitive to pH in the pH range of 5.5 to 8.6 (Zhu et al., 2005) · PtOEP: Platinum <<12,13,17,18-octaethyl-21H,23H-porphyrin Fluorescent dye sensitive to pH · Pt-PFP: Platinum(II) mesotetra(pentafluorophenyl)porphyrin Range 0% > O 2 > 21% of O 2 Fluorescent dye sensitive to · Ruthenium(II) diimine complex with trimethylsilylpropanesulfonate as a counterion: Ruthenium(II)-tris-4,7-diphenyl-1,10-phenanthroline Range 0% > O 2 > 21% of O 2 Fluorescent dye sensitive to

[0044] The xerogel may be produced from an organometallic compound, particularly one of the organometallic compounds listed above, or by an organometallic compound, particularly one of the organometallic compounds listed above, and by an organically modified silicate. In relation to the application, ultrafine glass powder or dual-core CoralPor (R) particles may be added to the mixture. The porous structure can be used for the distribution of the organometallic substance in the sol-gel matrix. The concentration in the pores can form a criterion. Thereby, the sensor sensitivity and response time are improved. This kind of mixture is a lumophore or lumophore substance and can be stored in the substrate by an accommodating means, particularly a cavity. For example, the lumophore is pO 2 , pCO 2、pH, temperature, etc. may be filled in corresponding cavities respectively and may be fixed by heat here.

[0045] In addition to the above-mentioned metal-organic compounds, the lumophore substance may further contain ground glass powder. In particular, such substances may be manufactured or may be manufacturable by the sol-gel method and may be used, for example, as xerogels.

[0046] The multi-sensor component may be configured as follows. That is, at least one sensor unit may be insertable, clip-fastenable and / or lockable and fixable to the front housing part, and / or at least one holding part may be configured for the insertion, clip-fastening and / or locking of the sensor unit. Further, the holding part may be configured for the contact of the sensor unit.

[0047] Therefore, in particular, the biosensor selected for each culture may be clip-fastenable or contactable to the guide part of the housing, for example, in the form of a biosensor chip.

[0048] Therefore, overall, the above-mentioned multi-sensor component is a universal and diverse adaptation system. Such a unique sensor concept enables the realization of diverse systems, for example, based on the above-mentioned multi-sensor component and in combination with various organometallic compounds and / or biosensor chips.

[0049] The structural form is basically designed for the universal availability for various types of receiving openings. Advantageously, the structural form may also be designed for standard ports (standard connections) of conventional bioreactors, disposable bioreactors or single-use bioreactors or ports of bags or for use in shaking flasks.

[0050] A multi-sensor unit with maintaining the requirements for aseptic culture conditions finds advantageous use. Thus, in an advantageous embodiment, a sensor housing extending through a port of a container forms a housing opening for a multi-sensor component. This type of sensor housing is in particular configured to maintain a sterile boundary between the culture space and the sensor. Further, in order to maintain aseptic culture conditions, the multi-sensor component may be or may be made aseptic before its secure housing in the housing opening.

[0051] The present invention further relates to a system for installing at least two sensors in individual ports of a container for culturing biological materials, in particular a bioreactor or an Erlenmeyer flask. Here, this system includes a sensor housing and a multi-sensor component as described above.

[0052] The sensor housing has an inner housing opening, where the sensor housing is insertable into the port of the container by at least a front sensor housing portion, and thus, the inner housing opening of the sensor housing extends through the port of the container.

[0053] The multi-sensor component has a housing, and this housing is insertable into the housing opening of the sensor housing extending through the port of the container by at least a front housing portion, and thus, the front housing portion is directed towards the inside of the container.

[0054] The housing of the multi-sensor component is configured as follows in an advantageous embodiment. That is, it is configured to be completely insertable into the housing opening extending through the port of the container, that is, in the state of use, in particular completely surrounded by the sensor housing in the radial direction. Thus, the housing of the multi-sensor component has, in particular, a non-changing outer shape along the longitudinal direction of the multi-sensor component, that is, it may be configured in particular cylindrically along the entire length of the multi-sensor component.

[0055] The receiving opening inside the sensor receiving part is in particular open towards the outside of the container, and thus the multi-sensor component can in particular be inserted into the receiving opening from the outside. Advantageously, the inner receiving opening has a constant cross-section along its longitudinal direction, i.e., in particular, it is configured in a cylindrical shape over the longitudinal part including the end part of the receiving opening that is open towards the outside.

[0056] In this system, the sensor receiving part may be configured to be closed in the front sensor receiving part. Thus, the receiving opening inside the sensor receiving part is open towards the outside of the container and closed towards the inside of the container when the sensor receiving part is inserted into the port of the container.

[0057] The front sensor receiving part has at least regionally an open porosity. The pore size is, for example, between 40 and 300 nanometers.

[0058] Furthermore, the present invention also relates to a container for culturing biological materials, in particular a bioreactor or a shaking flask, which includes a port. This port typically connects the inside of the container to the outside of the container. This container further has a multi-sensor component and optionally also a sensor receiving part.

[0059] The sensor receiving part has an inner receiving opening. Here, the sensor receiving part is inserted into the port of the container by at least the front sensor receiving part. Thus, the inner receiving opening of the sensor receiving part extends through the port of the container. The multi-sensor component with a housing is inserted into the receiving opening of the sensor receiving part that extends through the port of the container by at least the front housing part. Thus, the front housing part is directed towards the inside of the container.

[0060] In the case where there is no sensor housing part, the port connecting the inside of the container to the outside of the container forms an accommodation opening extending through the port. In this case, the multi-sensor component with the housing is inserted into the accommodation opening of the sensor housing part extending through the port of the container by at least the front housing part, and thus, the front housing part is directed towards the inside of the container.

[0061] The present invention further relates to a lumophore unit for measuring the parameters of a luminescence base, particularly for attachment to a multi-sensor component provided with a holding part for holding a lumophore unit as described above, for example. Regarding the details and / or further embodiments of the lumophore unit, the above description is correspondingly applicable.

[0062] Furthermore, the present invention relates to a method for manufacturing a multi-sensor component as described above, for example.

[0063] In a variation of the method, first, a sensor unit, particularly a lumophore unit as described above, for example, and a housing may be provided. The housing provided here can be inserted into the accommodation opening extending through the port of the container by at least the front housing part, and thus, the front housing part is directed towards the inside of the container. The housing provided here further has an accommodation part for the sensor unit, particularly the lumophore unit, in the front housing part. Here, the housing preferably contains or is composed of a polymer material, particularly polyetheretherketone (PEEK).

[0064] Next, in a further step, the housing may be expanded relative to the sensor unit, which is done in particular by heating the housing. Next, the sensor unit may be placed into the expanded receiving portion of the housing expanded relative to the sensor unit. Next, the housing may likewise be contracted relative to the sensor unit in order to fixedly receive the sensor unit within this receiving portion. This is done in particular by cooling the housing.

[0065] In another variation of the method, first, a sensor unit, in particular a lumophore unit as described above, and a liquid polymer material for forming a housing may be provided, where the provided liquid polymer material contains in particular polyethylene or polypropylene, or consists of polyethylene or polypropylene.

[0066] Next, in a further step, the liquid polymer material may be supplied to the sensor unit from the outside and cured so as to form a housing for fixedly receiving the sensor unit.

[0067] Hereinafter, several special embodiments of the present invention, which should not be understood in a decisive way, will be described with reference to the accompanying drawings.

Brief Description of the Drawings

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DETAILED DESCRIPTION OF THE INVENTION

[0069] FIGS. 1 - 5 show various views of port 100 in the wall 20 of the bioreactor. Here, the wall 20 of the bioreactor, shown only regionally, separates the inside of the bioreactor from the outside. In the example shown here, this is, for example, a multi-use bioreactor made of stainless steel that is used multiple times. However, similarly, for example, a single-use bioreactor made of plastic that is used only once or generally another container having port 100 may be used.

[0070] In the example shown here, port 100 present within the wall 20 of the bioreactor, which provides a through-hole through wall 20, is configured as an Ingold port or Ingold connection. However, basically, various ports 100 that form an opening through wall 20 are possible. Another standard port is, for example, a Broadly-James port or a B.-Braun safety port.

[0071] The wall 20 of the bioreactor has an inner surface 22 facing inward and an outer surface 24 facing outward. The inner surface 22 of the wall 20 faces the inner surface of the bioreactor and should be classified as a sterile area, and the outer surface 24 of the wall 20 faces the outer surface of the bioreactor and should be classified as a non-sterile area.

[0072] As best seen in FIG. 2, a sensor housing portion 200 is received within a port 100 that simultaneously forms a receiving opening 110 by virtue of its own through-opening into the interior of the container. The sensor housing portion 200 extends at least partially through a through-opening in a wall portion 20 formed by the port 100 and is held within the port 100. In the illustrated example, the sensor housing portion 200 is further removably locked or lockable to the port 100 by a cap nut 150. The sensor housing portion 200 projects into the interior of the container by virtue of a front sensor housing portion 210 and, in this embodiment, further projects outside the container by virtue of a rear sensor housing portion 220 in which a flange 225 is present.

[0073] The sensor housing portion 200 includes an inner receiving opening 230 which, in the illustrated example, is open towards a rear sensor housing portion 220 oriented outwardly. As illustrated, the receiving opening 230 may be closed towards a front sensor housing portion 210 oriented inwardly. Accordingly, the sensor housing portion 200 is also referred to as a "sterile port". The front sensor housing portion 210 may have at least regionally open porosity.

[0074] FIGS. 6-9 show various views of a shaking flask 10 with a shaking flask cap 12. The shaking flask cap 12 closes the opening 11 of the shaking flask 10 and includes the port 100 inside the shaking flask 10. The port 100 may similarly be various through-openings and, in particular, may be a standardized port.

[0075] As best seen in FIG. 7, a sensor housing portion 200 is also received within a port 100 that simultaneously forms a receiving opening 110 by virtue of its own through-opening into the interior of the container. The sensor housing portion 200 extends at least partially through the port 100 and is held within the port 100. In the illustrated example, the sensor housing portion 200 is removably locked or lockable to the port 100 by a locking element 150. The sensor housing portion 200 similarly includes an inner receiving opening 230. This is open towards the rear sensor housing portion 220 and closed towards the front sensor housing portion 210.

[0076] Referring to FIGS. 2 and 7, respectively, a multi-sensor component 300 is present within the receiving opening 230 of the sensor housing portion 200. In the case shown, the multi-sensor component 300 is fully inserted within the receiving opening 230 of the sensor housing portion 200 and is removably connected to a probe head 400, whereby the multi-sensor component 300 is insertable and again removable within the receiving opening 230. There may further be an electrical and / or optical connection between the probe head 400 and the multi-sensor component 300, whereby corresponding electrical and / or optical signals are transmissible.

[0077] FIGS. 10-14 show in detail various embodiments of the multi-sensor component 300. The embodiments of the multi-sensor component 300 each include a housing 305 having a front housing portion 310. The front housing portion 310 is best seen in FIGS. 10-12. The housing 305 further includes a rear housing portion 320, which is best seen in FIGS. 13 and 14.

[0078] In the front housing portion 310, a first sensor unit 350 and a second sensor unit 360 are arranged. With the multi-sensor component 300, at least two sensors can be installed at the individual ports of the container for culturing biological materials. The diameter of the housing 305 of the multi-sensor component 300 is sized as follows. That is, it is sized such that the multi-sensor component 300 can be completely inserted into the accommodation opening 230 of the sensor accommodation portion 200.

[0079] In the example shown in FIG. 10, one of the sensor units, here the first sensor unit 350, is configured as a modular biosensor unit 355. This is insertable in the front housing portion 310 at the corresponding holding portion 351. Simultaneously or independently thereof, one of the sensor units may be configured as a luminophore unit. Here, the second sensor unit 360 is configured as a luminophore unit 365. This is fixed to the front housing portion 310, which is done, for example, by it being fixedly accommodated by a recess in the front housing portion 310. For this purpose, in particular, a housing 305 may be provided that contains or is composed of polyetheretherketone (PEEK). This is manufactured, for example, by injection molding or also by, for example, additive manufacturing and is shrunk onto the luminophore unit 365, that is, expansion and contraction are carried out in particular to fix the luminophore unit 365. On the other hand, the housing 305 may also be manufactured together with the fixedly accommodated luminophore unit 365. This is done by the housing material being injected so as to coat around the luminophore unit.

[0080] In the example shown in FIG. 11, similarly, one of the sensor units, here the first sensor unit 350, is configured as a biosensor unit 355 held within a holding part 351. Simultaneously or independently thereof, similarly, one of the sensor units, here specifically the second sensor unit 360, may be configured as a lumophore unit 365. Different from the example shown in FIG. 10, in this example, the lumophore unit 365 is held within the holding part 361 by the front housing part 310. Thus, the lumophore unit 365 is held within the housing 305 or the holding part 361, particularly in a replaceable manner.

[0081] The embodiment of the multi-sensor component 300 shown in FIG. 12, similar to the example shown in FIG. 11, includes a housing 305 having a front housing part 310 and a rear housing part 320. Here, within the front housing part 310, a first holding part 351 for the first sensor unit 350 and a second holding part 361 for the second sensor unit 360 are arranged. The first holding part 351 is similarly configured here for holding the biosensor unit 355. Further, the second holding part 361 may be configured for holding the lumophore unit 365. Different from the example shown in FIG. 11, the multi-sensor component 300 does not include a sensor unit per se here.

[0082] The rear housing part 320 of the multi-sensor component 300, which is most clearly visible in FIGS. 13 and 14, may be configured differently, independent of the design of the front housing part 310. Advantageously, within the rear housing part 320, there is a connector 325 having electrical contact elements 326 and / or at least one optical contact element 327, thereby forming an electrical connection and / or an optical connection between the multi-sensor component and, advantageously, the sensor units held or fixed therein.

[0083] The connector 325 of the multi-sensor component 300 may in particular be designed to be connected to the probe head 400 (for which, see for example FIGS. 2 and 7). For example, the electrical contact element 326, which may be configured as a contact pin, is provided in particular for connection to the biosensor unit 355 or to the holding part 351 for holding the biosensor unit 355. On the other hand, however, the electrical contact element 326 may also be designed for connection to a light source arranged in the housing 305 and / or to a photo element, such as a photodiode, arranged in the housing. The multi-sensor component 300 does not necessarily have to include a light source or a photo element for the operation of the luminophore unit 365; rather, these components may be located outside the multi-sensor component 300. In such a case, one or more optical contact elements 327 may be provided, which may in particular be a light guide. In an advantageous embodiment, the luminophore unit 365 has a light guide configured as a fiber rod, in particular in the form of a rod, which leads to the connector 325 as can be seen in FIG. 14.

[0084] With reference to FIGS. 15 to 17, the sensor unit, in particular the biosensor unit 355 and the luminophore unit 365, will be referred to in more detail hereinafter. In FIG. 16, a replaceable luminophore unit 365 is shown, but this description applies equally to a luminophore unit 365 that is fixedly connected. This can be seen for example in FIG. 10. The biosensor unit 355 shown in FIG. 15 has the form of a flat unit, although other structural forms are possible. However, the biosensor unit 355 is preferably formed as follows. That is, the biosensor unit is formed so that it can be placed in the holding part 351 provided therefor and removed therefrom again. The biosensor unit preferably has a contact element 356, which may be configured as a contact surface that is contacted within the holding part 351.

[0085] The lumophore unit 365 shown in FIG. 16 includes a substrate 370 having a front substrate region 380 and a rear substrate region 390. The front substrate region 380, shown in detail again in FIG. 17, is configured as a glass disk, in which a plurality of cavities 382 for accommodating the lumophore material are formed by laser processing. The rear substrate region 390 is configured as a glass fiber rod, so that on the one hand, light can be guided from the light source to the cavity 382, and on the other hand, the luminescent light can be similarly guided from the cavity to a photo element, for example, a photodiode. The glass fiber rod may be connected to the glass disk containing the cavity 382 by laser welding. In the case of the replaceable lumophore unit 365, this may have a guide element 375 configured, for example, as a guide web, which cooperates with a complementary guide element 362 provided in the holding part 361 and configured, for example, as a guide groove, thereby ensuring the orientation of the lumophore unit 365 in its holding part 362. Such a guide web 375 and guide groove 362 are shown in FIG. 16 or FIG. 12.

[0086] This enables the overall use of a combination of a lumophore and a biosensor, where the lumophore unit 365 and the biosensor unit 355 are integrated in the housing 305. The lumophore may be filled individually into the cavity 382 here. This type of multi-sensor component enables the combination of optimal parameters for process control, such as pH, pO 2 , pCO 2 , temperature, concentration of saccharides, proteins, ions, impedance to cell growth, etc. in a selected measurement area at one port. On the other hand, the sole use of the lumophore at one port (or the sole use of the biosensor at one port) would not be able to control all of these parameters for process control.

Claims

1. A multi-sensor component (300) for installing at least two sensors at each individual port (100) of a container for culturing biological materials, wherein the multi-sensor component (300) comprises: a housing (305), which can be inserted into a receiving opening (110) extending through the individual ports (100) of the container by at least a front housing portion (310), whereby the front housing portion (310) faces the inside of the container and the housing (305); a first sensor unit (350) arranged at the front housing portion (310) and a first holding portion (351) for the first sensor unit (350); a second sensor unit (360) arranged at the front housing portion (310) and a second holding portion (361) for the second sensor unit (360); comprising: the first sensor unit (350) is configured as a biosensor unit (355) for measuring specimen-specific parameters; the biosensor unit (355) is configured as a modular unit and can be inserted into the first holding portion (351); the second sensor unit (360) is configured as a lumophore unit (365) for measuring light-emission-based parameters; the multi-sensor component (300).

2. The first holding portion (351) is configured for holding the biosensor unit (355). The multi-sensor component (300) according to Claim 1.

3. The biosensor unit (355) is configured in the form of a flat chip. The multi-sensor component (300) according to Claim 2.

4. The second holding portion (361) is configured for holding the lumophore unit (365). The multi-sensor component (300) according to any one of Claims 1 to 3.

5. The sensor unit (360) configured as a lumophore unit (365) includes a substrate (370) having accommodation means for accommodating a lumophore substance, wherein the accommodation means is configured within the substrate (370). The first holding portion (351) is configured for holding the substrate (370). The multi-sensor component (300) according to claim 4.

6. When the multi-sensor component (300) is inserted into the accommodation opening (110) extending through the port (100) of the container by at least the front housing portion (310), the front base region (380) is directed towards the inside of the container and the rear base region (390) is directed towards the outside of the container, the base (370) of the lumophore unit (365) has the front base region (380) and the rear base region (390), where the front base region (380) of the lumophore unit (365) includes at least one of the accommodation means, the rear base region (390) of the lumophore unit (365) includes a light source and / or a photo element, whereby light is guided from the light source to the accommodation means and / or light is guided from the accommodation means to the photo element or photo elements, The multi-sensor component (300) according to claim 5.

7. The front base region (380) is composed of a material containing glass or includes a material containing glass, where the accommodation means is incorporated as a cavity (382) within the material, The multi-sensor component (300) according to claim 6.

8. The rear base region (390) includes an optical fiber or is composed of an optical fiber, and the optical fiber forms a light guide for guiding light to the accommodation means, The multi-sensor component (300) according to claim 6 or 7.

9. The front base region (380) is configured in a disc shape, the rear base region (390) is configured in a rod shape and / or, the front base region (380) is connected to the rear base region (390) by laser welding, The multi-sensor component (300) according to any one of claims 6 to 8.

10. The lumophore unit (365) includes a lumophore substance, The multi-sensor component (300) according to any one of claims 4 to 8.

11. The lumophore substance includes graphene quantum dots (GQDs), heterocyclic GQDs and / or metal organic compounds, The multi-sensor component (300) according to claim 10.

12. At least one sensor unit is fixed to the front housing part (310) in an insertable, clip-fastenable and / or lockable manner. The first holding part (351) is configured for insertion, clip-fastening and / or locking of the sensor unit. The multi-sensor component (300) according to any one of claims 1 to 11.

13. A system for installing at least two sensors in individual ports (100) of a container for culturing biological materials, The system includes a sensor housing part (200) having an inner accommodation opening (230), wherein the sensor housing part (200) is insertable into the port (100) of the container by at least a front sensor housing part, and thus, the inner accommodation opening (230) of the sensor housing part (200) extends through the port (100) of the container. The system includes the multi-sensor component (300) according to any one of claims 1 to 12, the multi-sensor component (300) having a housing (305), the housing (305) being insertable into the accommodation opening (110) of the sensor housing part (200) that extends through the port (100) of the container by at least a front housing part (310), and thus, the front housing part (310) is directed towards the inside of the container. System.

14. The sensor housing part (200) is configured to be closed at the front sensor housing part, and thus, the inner accommodation opening (230) of the sensor housing part (200) is open towards the outside of the container and closed towards the inside of the container when the sensor housing part (200) is inserted into the port (100) of the container. The system according to claim 13.

15. The front sensor housing part has open porosity. The system according to claim 14.

16. A container for culturing biological materials, The container includes a port (100), the port (100) connecting the inside of the container to the outside of the container. The container includes a sensor housing portion (200) having an inner receiving opening (110), wherein the sensor housing portion (200) is insertable into the port (100) of the container by at least a front sensor housing portion, and thus the inner receiving opening (230) of the sensor housing portion (200) extends through the port (100) of the container. The container includes the multi-sensor component (300) according to any one of claims 1 to 12, the multi-sensor component (300) having a housing (305), the housing (305) being insertable into the receiving opening (230) of the sensor housing portion (200) that extends through the port (100) of the container by at least a front housing portion (310), and thus the front housing portion (310) is directed towards the inside of the container. Container.

17. A container for culturing biological materials, the container includes a port (100), the port (100) connecting the inside of the container to the outside of the container and forming a receiving opening (110) that extends through the port (100). The container includes the multi-sensor component (300) according to any one of claims 1 to 12, the multi-sensor component (300) having a housing (305), the housing (305) being insertable into the receiving opening (110) that extends through the port (100) of the container by at least a front housing portion (310), and thus the front housing portion (310) is directed towards the inside of the container. Container.

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