MULTI SENSOR FOR A BIOREACTOR, BIOREACTOR, METHOD FOR PRODUCING A MULTI SENSOR, AND FOR MEASURING PARAMETERS

Abstract

A multisensor and a process for the production of the multisensor for a bioreactor for use in cell culture and/or in microbiology is disclosed. The multisensor comprises at least three measurement arrangements configured to measure at least three parameters, where a first of the three measurement arrangements is configured to carry out an impedance measurement and/or a capacitive measurement, and where the first measurement arrangement has at least two electrodes which comprise an electrically conductive plasti.

Claims

1.-18. canceled

19. A multisensor for a bioreactor for use in cell culture or in microbiology, the multisensor comprising: at least three measurement arrangements configured to measure at least three parameters, wherein a first of the three measurement arrangements is adapted to carry out an impedance measurement or a capacitive measurement, and the first measurement arrangement includes at least two electrodes comprising an electrically conductive plastic.

20. The multisensor as claimed in claim 19, further comprising: an evaluation unit or an interface to the evaluation unit, wherein the evaluation unit is configured to measure impedance via the first measurement arrangement to derive data concerning a biomass situated in the bioreactor.

21. The multisensor as claimed in claim 20, wherein the data concerning the biomass situated in the bioreactor includes cell number, cell size, or cell viability.

22. The multisensor as claimed in claim 19, wherein a second measurement arrangement of the three measurement arrangements is configured to carry out an impedance measurement, a capacitive measurement, a fill-level measurement, or a foam measurement.

23. The multisensor as claimed in claim 22, wherein the second measurement arrangement includes at least two electrodes comprising an electrically conductive plastic.

24. The multisensor as claimed in claim 19, wherein a third measurement arrangement of the three measurement arrangements is configured to carry out a temperature measurement.

25. The multisensor as claimed in claim 19, wherein the first measurement arrangement, a second measurement arrangement, or a third measurement arrangement of the three measurement arrangements comprises two or more insulation sections entirely or partially comprising electrically nonconductive or insulating plastic.

26. The multisensor as claimed in claim 19, wherein the first measurement arrangement, a second measurement arrangement, or a third measurement arrangement of the three measurement arrangements are entirely or partially produced by molding.

27. The multisensor as claimed in claim 26, wherein: the first measurement arrangement, the second measurement arrangement, or the third measurement arrangement of the three measurement arrangements comprises at least one electrode produced by molding; the first measurement arrangement, the second measurement arrangement, or the third measurement arrangement of the three measurement arrangements comprises at least one insulation section produced by molding; or the first measurement arrangement, the second measurement arrangement, or the third measurement arrangement of the three measurement arrangements comprises at least one electrode and at least one insulation section produced by molding.

28. The multisensor as claimed in claim 19, wherein the multisensor is configured as a disposable multisensor.

29. The multisensor as claimed in claim 19, wherein the multisensor is configured as a one-piece multisensor or comprises two or more modules connected releasably or non-releasably to one another.

30. The multisensor as claimed in claim 19, wherein: a sensor element of the first measurement arrangement, a second measurement arrangement, or a third measurement arrangement of the three measurement arrangements located in the bioreactor is configured as a disposable unit; and the multisensory further comprises a measurement-electronics system configured as a reusable unit.

31. The multisensor as claimed in claim 19, further comprising a connector head adapted to be secured to a connection interface of the bioreactor.

32. The multisensor as claimed in claim 19, further comprising one or more further measurement arrangements for the measurement of parameters including pH, dissolved oxygen, carbon dioxide content, feedstock/product, or the concentration of metabolites including glucose, glutamate, glutamine, or ammonium.

33. The use of a multisensor as claimed in claim 19 for the measurement of at least three parameters in a bioreactor for use in cell culture and/or in microbiology.

34. A process for the measurement of at least three parameters in a bioreactor for use in cell culture and/or in microbiology, where the process comprises: provision of a multisensor as claimed in claim 19; carrying out an impedance measurement or capacitive measurement by using the first of the three measurement arrangements; and carrying out two further measurements by using a second measurement arrangement and a third measurement arrangement of the three measurement arrangements.

35. A bioreactor for use in cell culture and/or in microbiology comprising a multisensor, the multisensor further comprising: at least three measurement arrangements configured to measure at least three parameters, wherein a first of the three measurement arrangements is adapted to carry out an impedance measurement or a capacitive measurement, and the first measurement arrangement includes at least two electrodes comprising an electrically conductive plastic.

36. The bioreactor as claimed in claim 35, where the bioreactor is configured as a disposable bioreactor.

37. A process for the production of a multisensor for a bioreactor for use in cell culture or in microbiology, the multisensor comprising at least a first measurement arrangement, a second measurement arrangement, and a third measurement arrangement configured to measure at least three parameters, wherein the process comprises the step of: Integrating the at least first, second, and third measurement arrangements into the multisensor, where the first measurement arrangement is adapted to carry out an impedance measurement or a capacitive measurement, and the first measurement arrangement includes at least two electrodes comprising an electrically conductive plastic.

38. The process as claimed in claim 35, further comprising the step of: molding the first, the second, or the third measurement arrangements in its entirety as an integrated unit; molding the at least two electrodes of the first measurement arrangement or a one or more of an electrode of the second or the third measurement arrangements entirely or partially from electrically conductive plastic; molding one or more insulation sections of the first, the second, the third measurement arrangement entirely or partially from electrically nonconductive or insulating plastic; or molding the at least two electrodes of the first measurement arrangement or a one or more of an electrode of the second or the third measurement arrangement and one or more insulation sections of the first measurement arrangement.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0078] Preferred embodiments of the invention are described by way of example with reference to the attached figures.

[0079] FIG. 1 shows a three-dimensional depiction of a multisensor;

[0080] FIG. 2 shows a three-dimensional depiction of a part of a multisensor with a first measurement arrangement;

[0081] FIG. 3 shows a three-dimensional depiction of a part of a multisensor with a section of a second measurement arrangement; and

[0082] FIG. 4 shows a three-dimensional depiction of a disposable bioreactor with a multisensor.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0083] Elements that are similar or in essence have the same function are denoted in the figures by identical reference signs.

[0084] FIG. 1 shows a three-dimensional depiction of one variant of a multisensor 1. The multisensor 1 shown here has a primary linear-dimensional direction along the longitudinal axis X, where the linear dimension of the multisensor 1 along the longitudinal axis X is several times greater than a linear dimension that is orthogonal to the longitudinal axis. The multisensor 1 in the example shown here is configured in the shape of a rod and in essence has the shape of a cylinder. The cross section of the multisensor that is orthogonal to the longitudinal axis and primary linear-dimensional direction is circular.

[0085] At a first end of the multisensor 1, there is a connector head 600 arranged, with an interface 610 which is preferably suitable for electrical and/or communication connections.

[0086] The multisensor 1 comprises a first measurement arrangement 100, which is configured for an impedance measurement. The multisensor 1 further comprises a second measurement arrangement 200, which is configured to carry out a capacitive measurement and/or a fill-level measurement and/or a foam measurement. The multisensor 1 further comprises a third measurement arrangement 300, which is configured to carry out a temperature measurement.

[0087] The multisensor 1 can moreover also comprise further measurement arrangements for the measurement of further parameters, for example, pH and/or dissolved oxygen and/or carbon dioxide content and/or feedstock/product or concentrations of metabolites, for example: glucose, glutamate, glutamine, ammonium, etc.; these can by way of example be arranged at a second end 500, opposite to the first end of the multisensor 1.

[0088] The third measurement arrangement 300 is arranged on a component 400 with an integrated electronics system with a microcontroller and with an analog front end. The integrated electronics system of the component 400 can serve as evaluation unit, optionally also together with an external evaluation unit connected by way of the interface arranged in the connector head 600.

[0089] FIG. 2 is an enlarged depiction of a part of a possible variant of a multisensor with a first measurement arrangement 100. The first measurement arrangement 100 preferably comprises four electrodes 101, 102, 103, 104, which respectively are configured from electrically conductive plastic, or comprise electrically conductive plastic. The electrodes 101, 102, 103, 104 are separated and/or surrounded by insulation sections 111, 112, 113, 114, which consist of electrically nonconductive and/or insulating plastic or comprise same. The first measurement arrangement 100 is configured to carry out an impedance measurement. The electrodes 101, 102, 103, 104 are separated from one another by equal distances in the primary linear-dimensional direction of the multisensor 1. The electrodes 101 and 104 have a larger linear dimension in the primary linear-dimensional direction of the multisensor 1 than the two electrodes 102 and 103. The electrodes 101, 102, 103, 104 are arranged at a surface of the multisensor 1 and are arranged in a manner such that, during correct use in a bioreactor, they come into contact with fluids located in the reaction space of the bioreactor.

[0090] Preference is given to provision of an evaluation unit of the multisensor 1 and/or of an interface 600 of the multisensor 1 to an evaluation unit, where this evaluation unit is configured, on the basis of an impedance measurement, to derive data concerning biomass situated in the bioreactor, in particular, data concerning cell number and/or cell size and/or cell viability.

[0091] FIG. 3 is an enlarged depiction of a part of a multisensor with a section of a second measurement arrangement 200. The second measurement arrangement 200 is configured to carry out a capacitive measurement and/or a fill-level measurement and/or a foam measurement. The second measurement arrangement 200 moreover has a plurality of electrodes 201, which, in the example depicted here, are separated from one another by equal distances in the primary linear-dimensional direction of the multisensor 1 and comprise an electrically conductive plastic, or consist thereof. Again, these electrodes 201 are separated by insulation sections 202 and/or surrounded by insulation sections 202, where the insulation sections 202 consist of electrically nonconductive and/or insulating plastic, or comprise same. The resolution of the fill-level measurement and/or foam measurement can be influenced by way of the arrangement of the electrodes of the second measurement arrangement 200, in particular, the separation along the longitudinal axis X. The electrodes 201 are arranged beneath the surface of the multisensor and arranged in a manner such that, during correct use in a bioreactor, they do not come into direct contact with fluids located in the reaction space of the bioreactor. To this end, there are preferably also insulation sections configured on the electrodes 201, with the aim of preventing direct contact of the electrodes 201 with the fluids surrounding the multisensor 1, and of forming a protective external surface.

[0092] In FIG. 4, the multisensor 1 can be seen arranged in a disposable bioreactor 900. The disposable bioreactor 900 comprises a cover plate 920, a dimensionally stable container 910 and a stirrer unit 930. The cover plate 920 and the container 910 enclose a reaction space. The cover plate 920 has, facing toward the reaction space, an internal side on which a plurality of immersion tubes 940, 950 are arranged, projecting into the reaction space. On an external side of the cover plate 920, facing away from the reaction space, the arrangement has a plurality of connections on which flexible tubes and connection materials 970 and sterile filters 960 are arranged.

[0093] When installed in the disposable bioreactor 900, the multisensor 1 is in essence arranged in vertical orientation, and therefore the connector head 600 of the multisensor 1 is arranged at the cover plate 920 of the disposable bioreactor 900, and the multisensor 1 projects along its primary linear-dimensional direction therefrom into the reaction space of the disposable bioreactor 900.

[0094] The stirrer unit 930 comprises a stirrer shaft 310 with an axis of rotation and with two stirrer elements configured here with blades inclined by 45, for example, in the form of pitch blade impeller. Alternatively, it is also possible, by way of example, to use a Rushton impeller as stirrer element. The stirrer elements have been secured in rotationally rigid manner on the stirrer shaft, so that when the stirrer shaft rotates the stirrer elements rotate concomitantly.

[0095] The cover plate 920 and the container 910 can, by way of example, be configured from polyamide, or can comprise polyamide, and can have been bonded non-releasably to one another by means of ultrasound welding. The stirrer unit 930, in particular, the stirrer shaft and/or the stirrer elements, can, by way of example, be configured from polystyrene, or can comprise polystyrene.

[0096] Flexible tubes and connection materials 970 which used with the disposable bioreactor 900 and which can come into contact with reaction media, are preferably configured from materials certified in accordance with United States Pharmacopeia (USP) class VI, for example, polystyrene, polycarbonate, polyamide, or silicone. The flexible tubes to be used are preferably flexible tubes made of thermoplastic elastomers.

[0097] The use of a multisensor 1 in the disposable bioreactor 900 permits use of one connection on the cover plate 920 for the measurement of three (or more) parameters. As can be seen by way of example in FIG. 4, space on the cover plate is limited, but at the same time the number of elements requiring connection here is large. Integration of three sensors into a multisensor is, therefore, especially advantageous, in particular, when the first measurement arrangement is suitable for an impedance measurement and/or for a capacitive measurement.

[0098] The use of electrically conductive plastic in the electrodes moreover permits achievement of low-cost design for the multisensor, and this, in particular, also permits configuration thereof as disposable multisensor. Access to further application sectors can thus be achieved.