SYSTEM, DEVICE AND METHOD FOR DETECTING AT LEAST ONE VARIABLE DURING A BIOLOGICAL OR CHEMICAL PROCESS

Abstract

A system for detecting at least one variable of a liquid sample (2) being moved in a container (1) during a biological or chemical process is disclosed. The container (1) comprises a bottom (5), a plurality of walls (3.sub.1, 3.sub.2), and an opening (4) opposite the bottom (5). A wall (3.sub.2) forms an obtuse angle () with the adjacent walls (3.sub.1) respectively. A reflection element (7) is formed on the wall (3.sub.2). A measuring unit (10) has a radiation source (11). A sensor (12) is assigned to the bottom (5) of the container (1) in such a way that a beam (11E) emerging from the radiation source (11) is directed to the reflection element (7) and from there through the wall (3.sub.2) to the sample in the container (1). The bottom (5) is transparent to a wavelength range of a radiation (11A) emerging from the sample (2). The sensor (12) of the measuring unit receives radiation (11A) from the sample (2). A device and a method for detecting at least one variable of liquid samples (2) during a biological or chemical process are also provided by the invention.

Claims

1. A system for detecting at least one variable of a liquid sample, the system comprising: a container formed by a bottom, a plurality of walls, and an opening opposite the bottom, wherein the container receives the liquid sample to perform a biological or chemical process in the container; a single wall of the container, forming an obtuse angle with the adjacent walls respectively; a reflection element is formed on the wall; and, a measuring unit having a radiation source and a sensor is assigned to the bottom of the container in such a way that a beam emerging from the radiation source is directed to the reflection element and from there through the wall to the liquid sample in the container, wherein the bottom is transparent for a wavelength range of a radiation emerging from the liquid sample, and the sensor of the measuring unit receives radiation from the sample.

2. The system according to claim 1, wherein the container is made of a plastic by means of an injection molding process, and the reflection element is an integral part of the container.

3. The system according to claim 1, wherein at least a portion of the wall assigned to the reflective element is transparent for a wavelength range of the beam from the radiation source, and wherein at least a portion of the bottom assigned to the sensor is transparent for a wavelength range of the radiation from the sample.

4. A device for detecting at least one variable of at least one liquid sample during a biological or chemical process, the device comprising: a measurement carrier a moving component for moving the measurement carrier in a combined movement composed of an X-coordinate direction and a Y-coordinate direction; a matrix of a plurality of containers rigidly connected to one another, each of the containers is defined by a bottom, a plurality of walls and an opening opposite the bottom; a base module of the matrix which is constructed of four containers connected to one another, the matrix being composed of a plurality of base modules which are also rigidly connected to one another; a central channel of the base module which defines a respective wall of each of the four containers; an end of the channel of the base module which defines four reflection elements, one respective reflection element being assigned to the wall of each container of the base module; and a plurality of measuring units arranged in the measurement carrier, each measuring unit having at least one controllable radiation source of electromagnetic radiation and at least one sensor for detecting electromagnetic radiation, wherein the plurality of measuring units is arranged in a distribution throughout the measurement carrier in a way such that, when the matrix is seated on the measurement carrier, one respective radiation source is assigned to each reflection element of each container and at least one respective sensor is assigned to the bottom of each of the containers.

5. The device according to claim 4, wherein a plurality of stops is provided which position the matrix in an accurately aligned manner on the measurement carrier, and each container of the matrix is assigned a respective measuring unit such that each reflection element of each container is assigned a radiation source and each bottom is assigned a sensor.

6. The device according to claim 4, wherein the bottom of each container of the matrix is configured such that it is transparent to the electromagnetic radiation from the controllable radiation source into the liquid sample and to the electromagnetic radiation emanating from the liquid sample to the at least one sensor.

7. The device according to claim 4, wherein the radiation source is at least one light-emitting diode, wherein an optical system for guiding and forming the electromagnetic radiation is arranged downstream of said at least one light-emitting diode.

8. The device according to claim 7, wherein the optical system is composed of at least one pinhole aperture and an optical lens, the optical lens collimating the electromagnetic radiation in the liquid sample into a beam.

9. The device according to claim 4, wherein the moving component is configured to move the measurement carrier in the X-coordinate direction and in the Y-coordinate direction with a defined, radial, and orthogonal to the gravitational force extending movement about a fixed axis.

10. The device according to claim 4, wherein the measurement carrier is provided with an electronic module which is communicatively connected to each sensor of each measuring unit, and the electronic module is connected to a base station via a data connection.

11. The device according to claim 4, wherein the moving component is dimensioned such that up to ten measurement carriers can be placed on the moving component, whereby an uninterrupted, non-invasive, and simultaneous measurement on a plurality of containers of a matrix on a plurality of measurement carriers can be carried out.

12. The device of claim 11, wherein at least one incubator is provided, in which the moving component and the at least one measurement carrier are accommodated.

13. The device of claim 12, wherein a plurality of measurement carriers are positioned in a plurality of incubators such that the measurement carriers are subject to different incubation environments and movement patterns of the moving component.

14. A method for detecting at least one variable of a liquid sample during a biological or chemical process, the method comprising the steps of: filling at least one container of a matrix of a plurality of containers with the liquid sample, the matrix being made up of a plurality of base modules, each base module being composed of four containers connected to one another, wherein a central channel defines a respective wall of each of the containers, and an end of the channel of the base module defines four reflective elements, wherein a respective reflection element is assigned to the respective wall of each container of the base module; placing the matrix on a measurement carrier such that each of the plurality of measuring units arranged in the measurement carrier is assigned to one of the containers of the matrix, so that at least one controllable radiation source of the measuring unit is assigned to the reflection element of each container, and at least one sensor of the measuring unit is assigned to a bottom of each container; moving the measurement carrier in the X coordinate direction and in the Y coordinate direction, wherein the movement of the measurement carrier is performed radially and orthogonal to the gravitational force about a fixed axis, and wherein in each base module of the matrix, depending on the movement, the liquid sample alternately accumulates on the wall of each container of the base module; triggering the at least one controllable radiation source of each measuring unit in such a way that via reflection element and the wall of each container, electromagnetic radiation is irradiated into the sample just accumulated on the wall of the respective container; and collecting, with the respective sensor of the respective measuring unit, the electromagnetic radiation emerging through the respective bottom of each container of the matrix, wherein a determination of the at least one variable during the biological or chemical process is performed in the at least one container of the matrix.

15. The method according to claim 14, wherein a beam of the measuring unit emerging from the radiation source is irradiated through the wall into the respective container of the base module or matrix, and wherein the optical sensor of the measuring unit receives the electromagnetic radiation emerging through the bottom from the liquid sample accumulated on the wall of each container.

16. The method according to claim 14, wherein the containers of the matrix are measured with their assigned measuring units of the measurement carrier in such a way that the containers in the base module are grouped, and measured values are obtained from the containers of each base module with a time delay.

17. The method according to claim 14, wherein the at least one variable in each container of the matrix is recorded in a defined measurement interval with a measurement frequency of at least 50 measurement events per second, and wherein the recorded measurement data of the at least one variable of each container of the matrix are processed independently of one another according to a mathematical method in a defined time measurement interval and converted into a value of the variables determined temporally after the beginning of the process.

18. The method according to claim 17, wherein the measured values obtained with a time delay are transmitted to a base station by means of a data connection.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0071] The nature and mode of operation of the present invention will now be more fully described in the following detailed description of the invention taken with the accompanying figures, in which:

[0072] FIG. 1A shows a schematic side view of a container with a square cross-section used in the system according to the invention for a sample with the assigned measuring unit comprising a radiation source and a sensor;

[0073] FIG. 1B shows a schematic side view of another embodiment of a container used in the system according to the invention for a sample with the assigned measuring unit of radiation source and sensor;

[0074] FIG. 1C shows a perspective view of the container when used in the system according to the invention, wherein a liquid mountain builds up in the container during a shaking movement;

[0075] FIG. 2 shows a plan view of a base module for a matrix of a plurality of containers, each of the containers having the same cross-sectional shape;

[0076] FIG. 3 shows a sectional view of the base module along the section line marked A-A in FIG. 2;

[0077] FIG. 4 shows a plan view of an embodiment of a matrix of a plurality of rigidly interconnected containers, which substantially correspond to the embodiments described in FIGS. 1-2;

[0078] FIG. 5 shows a plan view of an embodiment of a matrix of a plurality of rigidly interconnected containers, wherein the matrix is mounted stationarily on a measurement carrier;

[0079] FIG. 6 shows an enlarged view of the area marked B in FIG. 5;

[0080] FIGS. 7A-7B each show a cross section of an embodiment of the optical system for collimating the electromagnetic radiation emitted by the radiation source;

[0081] FIG. 8 shows a plan view of the rigidly connected containers of the matrix, wherein only those containers of the matrix are filled with the liquid sample, which form a sufficient accumulation (collection) of the liquid sample for measurement during the movement of the measurement carrier on the wall with the reflection element;

[0082] FIG. 9 shows a plan view of the rigidly connected containers of the matrix, wherein the containers of the matrix are filled in groups with the liquid sample, so that during the movement of the measurement carrier, on the wall with the reflection element, an accumulation of the liquid sample sufficient for the measurement is formed;

[0083] FIG. 10 shows a sectional view of the matrix of the containers, wherein the matrix is seated on a measurement carrier according to an embodiment;

[0084] FIG. 11 shows a plan view of an arrangement of the matrix of a plurality of containers in rigid connection to one another according to another embodiment of the measurement carrier;

[0085] FIG. 12 shows a sectional view along the section line B-B, which is marked in FIG. 11, of the measurement carrier for the matrix of the containers, wherein the measurement carrier is placed on a moving component;

[0086] FIG. 13 shows the arrangement of a plurality of microtiter plates with the rigidly interconnected containers in an incubator;

[0087] FIG. 14 shows a schematic arrangement of an incubator to a computer, which provides for the recording and evaluation of the measurement results of the substances in the containers of the microtiter plates, which are introduced in the incubator; and,

[0088] FIG. 15 shows a flow chart of an embodiment of the method according to the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0089] The drawings merely show embodiments of how the one or more containers according to the invention or the device according to the invention can be configured. The drawings expressly do not limit the invention to these embodiments. At the outset, it should be appreciated that like reference numbers on different figures identify identical, or functionally similar, structural elements of the invention. It is to be understood that the invention as claimed is not limited to the disclosed aspects.

[0090] Furthermore, it is understood that this invention is not limited to the particular methodology, materials, and modifications described and as such may, of course, vary. It is also understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to limit the scope of the present invention as claimed.

[0091] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention pertains. It should be understood that any methods, devices or materials similar or equivalent to those described herein can be used in the practice or testing of the invention.

[0092] Referring now to the figures, FIGS. 1A, 1B, and 1C show different views and embodiments of a container 1 according to the invention, which can be used in the system according to the invention. The embodiments shown in FIGS. 1A, 1B, and 1C are not to be construed as limiting the invention. The container 1 can be used individually or in the form of a matrix 1M (see FIG. 4).

[0093] FIG. 1A shows a schematic side view of the embodiment of a container 1. The container 1 serves to receive a liquid sample 2. In the system according to the invention, each container 1 is assigned a measuring unit 10. The liquid sample 2 is a fluid medium (liquid), which is present in the form of for example, a solution, an emulsion, or a suspension. The liquid sample 2 may also be a fluid medium in which microorganisms develop. As can be seen from the illustration of FIG. 1C, the container 1 is constructed from a bottom 5 and a plurality of walls 3.sub.1 connected to the bottom 5. Opposite the bottom 5, an opening 4 is provided, through which the container 1 can be filled with the liquid sample 2. If necessary, the opening 4 of the container 1 or the containers 1 can be closed with a cover 6 (see FIG. 10).

[0094] As can be seen from the illustration of FIG. 1C, the container 1 has a substantially square bottom surface 15. In addition, a wall 3.sub.2 is provided which encloses an obtuse angle with the adjacent walls 3.sub.1 in each case. On the wall 3.sub.2, a reflection element 7 is formed. Each container 1 is assigned to a measuring unit 10, which has a radiation source 11 and a sensor 12. The measuring unit 10 is provided in a measurement carrier 22. In an correctly aligned placement of the container 1 on the measurement carrier 10, the radiation source 11, the reflection element 7, and the sensor are assigned to the bottom 5. For the measurement on the fluid sample 2 and/or for the cultivation, the container 1 is moved (agitated) in a suitable manner. Sample 2 is a fluid medium (liquid) which is present, for example, in the form of a solution, an emulsion, or a suspension. The fluid sample 2 may also be a fluid medium in which microorganisms develop.

[0095] A beam 11E is directed from the radiation source 11 through the wall 3.sub.2 onto the liquid sample 2 in the container 1 via the reflection element 7. Preferably, the beam 11E is then directed to the sample 2 when, due to the movement, the fluid sample 2 has accumulated on the wall 3.sub.2. This has the advantage that a sufficiently large amount of the fluid sample 2 is available for the measurement. The sensor 12 of the measuring unit 10 detects the radiation 11A emerging from a scattering region 14 of the fluid sample 2 through the bottom 5. For this purpose, the bottom 5 itself or at least a portion 5F of the bottom 5 is transparent for a wavelength range of the radiation 11A emanating from the scattering region 14.

[0096] The reflection element 7 is an integral part of the wall 3.sub.2. Preferably, the container 1 is produced by means of an injection molding process from a plastic. The embodiments of the container 1 shown in FIGS. 1A and 1B differ in that the reflection element 7 is attached to the wall 3.sub.2 at a different height H in each case. The reflection element 7 is preferably arranged such that the beam 11E from the radiation source 11 passes through the wall 3.sub.2 substantially perpendicularly. According to an embodiment, the wavelength of the beam 11E (light) emanating from the radiation source 11 is 600 nm to 900 nm.

[0097] The bottom 5 or the portion 5F of the bottom surface of each container 1 is configured such that it is transparent in an orthogonal direction R for electromagnetic radiation 11A (light) from the sample 2. At least one measurement on the sample 2 is for obtaining information by an optical method, wherein the determination of at least one variable (such as, for example, turbidity, biomass, or cell concentration) is made during an uninterrupted, defined, radial movement of the container or containers 1 about a fixed axis A, wherein the movement is orthogonal to the gravitational force. The radius of the movement may be between 0.5 mm and 50 mm. The frequency of the movement may be between 0 and 2000 revolutions per minute (rpm).

[0098] FIG. 2 shows a plan view of a base module 100 for a matrix 1M (see FIG. 4) of a plurality of containers 1. Each of the containers 1 has the same cross-sectional shape. Each of the containers 1 of the base module 100 is bounded laterally by the walls 3.sub.1 and the wall 3.sub.2, which is assigned to the reflection element 7. The entire matrix 1M (see FIG. 4) and thus also the base module 100 can be produced by an injection molding process. The injection molding process can be configured as one-, two- or multi-component injection molding. The base module 100 is constructed from four containers 1 connected to one another. A central channel 102 is assigned to each of the containers 1 of the base module 100. Through the central channel 102, in each case a wall 3.sub.2 of each of the four containers 1 is defined, which wall 3.sub.2 carries the reflection element 7. In the embodiment shown here, the channel 102 has a square cross-sectional shape.

[0099] FIG. 3 shows a sectional view of the base module 100 along the section line A-A marked in FIG. 2. The matrix 1M and thus also the base modules 100 can be manufactured with a suitable tool in an injection molding process. The channel 102 has an end 104 which has the shape of a pyramid. The pyramid defines the reflection element 7 for each of the four walls 3.sub.2 of the base module 100. When the matrix 1M with the base modules 100 is placed on the measurement carrier 22, the sensor 12 of each measuring unit 10 is assigned to the reflection element 7. Likewise, the sensor 12 of each measuring unit 10 is assigned to the bottom 5 of each container 1.

[0100] FIG. 4 shows a plan view of an embodiment of a matrix 1M comprising a plurality of containers 1 which are rigidly connected to one another, and the containers 1 essentially correspond to the embodiments of the containers 1 described in FIG. 1 or FIG. 2. In the embodiment shown here, the matrix 1M consists of six base modules 100. The matrix 1M thus comprises twenty-four containers 1. It will be understood by a person skilled in the art that the number of containers 1 of the matrix 1M should not be construed as limiting the invention.

[0101] FIG. 5 shows a plan view of an embodiment of a matrix 1M comprising a plurality of containers 1 (microbioreactors, wells) which are rigidly connected to one another and which are mounted in a stationary manner on a measurement carrier 22. For this purpose, a plurality of positioning aids 27 (stops) are provided on the measurement carrier 22. By means of the positioning aids 27 it is ensured that when placing the matrix 1M on the measurement carrier 22, each container 1 of the matrix 1M the radiation source 11 and the sensor 12 of the measuring unit 10 are assigned at defined positions.

[0102] The assignment of the radiation source 11 and the sensor 12 of the measuring unit 10 to the containers 1 is illustrated in FIG. 6 on the basis of an enlarged illustration of the area marked B in FIG. 6. For this purpose, a base module 100 of the matrix 1M is shown enlarged. The radiation source 11 of the measuring unit 10 is assigned to the reflection element 7 of a container 1 in the matrix 1M placed on the measurement carrier 22. The sensor 12 of the measuring unit 10 is then assigned to the bottom 5 or a portion 5F of the bottom 5, which is transparent to the electromagnetic radiation 11A (light) emanating from the sample 2. The shape and that of the portion 5F of the bottom 5 should not be construed as limiting the invention.

[0103] FIGS. 7A-7B each show a cross section through an embodiment of the optical system 13 for collimating the electromagnetic radiation emitted by the radiation source 11. In one embodiment, the radiation source 11 consists of the light-emitting diode 26 followed by an optical system 13. The optical system 13 is composed of a spacer 71, at least one pinhole aperture 72, a further spacer 73, an optical lens 74 and a spacer 75. The pinhole aperture 72 serves to reduce the specific radiation angle of the light-emitting diode 26. The light cone emerging from the pinhole aperture 72 is focused by means of the optical lens 74, whereby a high depth of focus of the projection is achieved.

[0104] FIG. 8 shows a plan view of the rigidly connected containers 1 of the matrix 1M, wherein only those containers 1 of the matrix 1M are filled with the liquid sample 2, which containers 1 form, during the movement of the measurement carrier 22, at substantially the same time on the wall 3.sub.2 with the reflection element 7, an accumulation of the liquid sample 2 sufficient for the measurement.

[0105] FIG. 9 likewise shows a plan view of the rigidly connected containers 1 of the matrix 1M. Here, all containers 1 of the matrix 1M are filled with a liquid sample 2. The different patterns of the containers 1 of each base module 100 of the matrix 1M indicate that during the movement of the measurement carrier 22, the accumulation of the liquid sample 2 at different times in each container 1 of each base module 100 on the wall 3.sub.2 with the reflection element 7 occurs. The different pattern filling of the containers 1 represents the division of the containers 1 into groups. According to an embodiment, the measurement, if a sufficient accumulation of the liquid sample 2 is formed in the respective container 1, is carried out in a clocked manner. This means that the radiation sources 11 of the containers 1 of a specific group are switched on at the same time.

[0106] FIG. 10 shows a side view of the matrix 1M, which consists of the plurality of rigidly connected containers 1 arranged on an embodiment of the measurement carrier 22. The measurement carrier 22 serves to receive the matrix 1M of containers 1 (microbioreactors, wells). In this embodiment, all containers 1 are covered with a cover 6 during the measuring process. The cover 6 is provided with bores 6B. Each of the containers 1 is assigned to a bore 6B. The cover 6 is a sterile barrier in the form of a membrane or other porous semipermeable layer. The sterile barrier allows the gas exchange in both directions, whereby, for example, microorganisms are supplied with oxygen or metabolic products such as CO.sub.2 are discharged. The measurement carrier 22 carries the plurality of measuring units 10 at defined positions which are assigned to the bottom 5 of each container 1 fixed in each case in the matrix 1M placed on the measurement carrier 22. The measurement carrier 22 further comprises an electronic module 24, which is in communication with the measuring units 10. The power supply of the measuring units 10, the electronic module 24 and the data connection 23 is carried out in a manner known in the art.

[0107] FIG. 11 shows a plan view of a matrix 1M comprising a plurality of containers 1, wherein the matrix 1M is positioned in an exact position (accurately aligned) on the measurement carrier 22. In the embodiment shown here, the measurement carrier 22 has further formed an electronic module 24, which provides for the power supply of the individual measuring units 10 and a communication to measuring units 10 (within a sensor network) on the measurement carrier 22 via connection technologies known in the art. A data connection 23 to a base station 30 or computer (see FIG. 14) is provided. The data connection 23 is a wireless communication in the embodiment described herein. Through the communication with the base station 30 or computer (for data processing and/or data recording), the active containers 1 filled with a sample 2 and the at least one measurement carrier 22 of the measuring system can be combined to form a communicating network of the measuring units 10.

[0108] FIG. 12 shows a sectional view along the section line B-B of the measurement carrier 22 marked in FIG. 11 and the matrix 1M placed thereon. The measurement carrier 22 is placed on a moving component 25. In this way, the matrix 1M of the containers 1, which is stationarily connected to the measurement carrier 22, can be affected with a defined movement. For the measurement on the sample 2 in the individual containers 1 and the determination of at least one variable of the sample 2, an uninterrupted, defined, radial, and orthogonal to gravitational force movement of the matrix 1M of the containers 1 on the measurement carrier 22 can be carried out about a fixed axis A. The movement is composed at least of movement components in an X-coordinate direction X and/or a Y-coordinate direction Y. The individual containers 1 of the matrix 1M are assigned on the measurement carrier 22 in a stationary manner to the measuring units 10 of the measurement carrier 22 for the determination of the at least one variable of the sample 2. The measured values of the measuring units 10 are transmitted to the base station 30 (see FIG. 14) with the electronic module 24 or the data connection 23.

[0109] FIG. 13 shows the arrangement of a plurality of measurement carriers 22, each having a matrix 1M arranged thereon of a plurality of containers 1 in an incubator 40. In the measuring system shown here, ten measurement carriers 22 (measuring units) are introduced in the incubator 40 with a matrix 1M of in each case twenty-four containers 1 arranged thereon for the samples 2. This achieves a continuous, optical measurement and recording of scattered light which is produced on the biological material in the individual containers 1 as a result of the irradiation with light. By means of a single measurement carrier 22, an uninterrupted, non-invasive, and simultaneous measurement can be carried out on the twenty-four containers 1 per measurement carrier 22 during the use in incubators 40 for bacterial and mammalian cell cultures in the radial shaking mode. By miniaturization of the measurement carrier 22, up to ten measurement carriers 22 can be arranged and operated simultaneously within a shaker or incubation environment. The communication of the individual measuring units 10 assigned to the containers 1 of the respective carrier 22 (measuring unit) is controlled by the electronic module 24. The communication of the measuring units 10 is carried out via a respective data connection 23, for example, a radio connection (Bluetooth, WLAN).

[0110] FIG. 14 shows a schematic arrangement of an embodiment of an incubator 40 in conjunction with a base station or computer 30, which carries out the recording and evaluation of the measurement results of the substances in the containers 1 (microbioreactors). To support the processes of interest in a respective test, the measurement carriers 22 with the plurality of containers 1 can be moved in the incubator 40. This is preferably done mechanically. Corresponding devices known in the art are, for example, shakers or rockers. Such devices are commercially available in various embodiments, which can move a container 1, but also a plurality of containers 1, on a measurement carrier 22 simultaneously in a defined manner. All these devices have adequate space in the incubator 40. The base station 30 is connected to the incubator 40 via a bidirectional communication connection 35 to receive data from the measurement carriers 22 in the incubator 40, and, for example, to send control data from the base station 30 to the incubator 40 itself or to the electronic modules 24 of the carrier 22.

[0111] According to a preferred embodiment, each measuring unit 10 has a data connection 23, which is a radio transmitter or receiver, with which a local radio network is established as a permanently stationed, central data connection 23Z, being also a radio transmitter or receiver. In the data transfer technology used, for example, Bluetooth or WLAN can be used. All measuring units 10 also have a device-internal, permanent data memory for recording measurement data. The central radio transmitter or receiver is connected via a data interface 23D to a base station 30 (data processing and/or data recording device), such as, for example, a computer such as, for example, a desktop computer, a notebook computer, a tablet computer or a smart phone.

[0112] A flow chart of the method according to the invention of the parallelized detection of cell and biomass concentrations of cell cultures (liquid sample 2) is shown in FIG. 15. In a step 61 at the beginning of the method according to the invention, at least one container 1 of a carrier 22 is filled with a liquid sample 2 (constitution and properties of the sample are described sufficiently above). The containers 1 are arranged regularly in columns 9 and lines 8, in the form of a matrix, stationary on the carrier. The opening 4 of the containers 1 can be closed with a cover 6 (see FIG. 10) so that the liquid sample 2 does not pass beyond the container 1 during the measuring process or the cultivation.

[0113] In a next step 62, the at least one measurement carrier 22 is placed on a moving component 25. The measurement carrier 22 and the moving component 25 can be introduced into at least one incubator 40, which is communicatively connected to the base station 30. It should be noted that in another embodiment of the method, the incubator can also be omitted.

[0114] In step 63, a measuring process and a shaker or incubation environment are set at the base station 30. The settings are transmitted to the at least one measurement carrier 22 and possibly to the at least one incubator 40 (if necessary also to the moving component 25). By setting the measuring process, the grouped containers 1 of a matrix can thus be measured with a time-delay. The setting of the measuring process can comprise, for example and without being limited thereto, the incubation conditions, the radial movement pattern (such as, for example, repetition frequency and direction of rotation, since the type of movement radial is previously predetermined) of the moving component 25, the control of the radiation source 11, the definition of the measurement frequency for a measurement time interval (for the generation of a measured value, the user only sets, for example, that every 10 seconds a measured value is to be detected), or the setting of the wavelength emitted by the radiation source 11.

[0115] In step 64, the movement of the at least one measuring carrier 22 is carried out with the moving component 25 assigned to the measurement carrier 22. During the movement of the measurement carrier 22 according to a defined movement pattern, the determination of a variable of the biological or chemical process is made. The movement of the carrier 22 may be performed, for example, continuously and with a defined, radial, and orthogonal to gravitational force S extending movement about a fixed axis A.

[0116] In a step 65 parallel in time to step 64, the measuring unit 10 acquires the measurement data of the liquid and moving sample 2 present in the at least one container 1. The acquiring (recordation) of the measurement data is carried out at a defined time measurement interval with a defined measurement frequency of at least 50 Hz. In each container 1, in which a sample is located, the measured data are recorded with the sensor 12 of the measuring unit 10. A respective measuring unit 10 is permanently assigned to the respective containers 1, the measuring units 10 being arranged stationarily on the measurement carrier 22 for the containers 1 (for example, a microtiter plate). The measuring unit 10 comprises the controllable radiation source 11 and the at least one sensor 12.

[0117] In step 66, finally, the transmission of the recorded measurement data of a variable in the at least one container 1 is carried out. The measurement data are transmitted from the incubator 40 to the base station 30 (or a suitable evaluation unit). The base station 30 is used to calculate the value of the variable determined by the evaluation process. The variable is, for example, the turbidity and the optical density of liquid samples, the cell density, biomass and cell concentration, pH value, O.sub.2 saturation of the liquid, or the ambient temperature. For the determination of the pH value or the O.sub.2 saturation of the liquid, sensor pads (not shown here) are glued into the container. The pH value or the O.sub.2 saturation are detected as an optical response by the sensor 12 assigned to the respective container, said sensor 12 having been previously illuminated with a light source. The relative saturation of dissolved oxygen in the respective sample 2 is regulated by a change in the energy input during the movement of the containers 1 or of the carrier 22 by the movement pattern of the moving component 25. It is particularly advantageous if the recorded measurement data are transmitted via a data connection 23 (for example, via radio) from the incubator 40 to the base station 30, since the source of error of a cable break is eliminated.

LIST OF REFERENCE NUMERALS

[0118] 1 Container [0119] 1M Matrix [0120] 2 Sample [0121] 3.sub.1 Wall [0122] 3.sub.2 Wall [0123] 5 Opening [0124] 5 Bottom, Base [0125] 5F Portion of the bottom [0126] 6 Cover [0127] 6B Bore [0128] 7 Reflection element [0129] 10 Measuring unit [0130] 11 Radiation source [0131] 11A Radiation from the sample [0132] 11E Beam from the radiation source [0133] 12 Sensor [0134] 13 Optical system [0135] 14 Scattering region [0136] 15 Bottom surface [0137] 22 Measurement carrier [0138] 23 Data connection [0139] 23D Data interface [0140] 23Z Central data connection [0141] 24 Electronic module [0142] 25 Moving component [0143] 26 Light-emitting diode [0144] 27 Positioning aid (stop) [0145] 30 Base station [0146] 35 Bidirectional communication connection [0147] 40 Incubator [0148] 61 Step [0149] 62 Step [0150] 63 Step [0151] 64 Step [0152] 65 Step [0153] 66 Step [0154] 71 Spacer [0155] 72 Pinhole aperture [0156] 73 Spacer [0157] 74 Optical lens [0158] 75 Spacer [0159] 100 Base module [0160] 102 Channel [0161] 104 End [0162] A Axis [0163] A-A Intersection line [0164] B Area [0165] B-B Intersection line [0166] H Height [0167] R Orthogonal direction [0168] S Gravitational force [0169] X X coordinate direction [0170] Y Y coordinate direction [0171] Z Z-coordinate direction [0172] Obtuse angle