Biotechnical analysis module and biotechnical analysis system

Abstract

A biotechnological analysis module (1) comprises a reactor (2) and an assembly (10) consisting of a microfluidic system (11) and a photonic circuit (12). The photonic circuit (12), together with the microfluidic system (11), encloses a sample volume (14) which is connected to the reactor (2). The microfluidic system (11) comprises at least one microfluidic channel (13) which is connected to the sample volume (14) and / or the reactor (2). The photonic circuit (12) comprises an optical waveguide assembly (19) arranged on the enclosed sample volume (14) such that light from the optical waveguide assembly (19) can be coupled into the enclosed sample volume (14) and / or that light from the enclosed sample volume (14) can be coupled into the optical waveguide assembly (19).Additionally or alternatively, the optical waveguide arrangement (19) is arranged on the at least one microfluidic channel (13) such that light which can be transmitted via the optical waveguide arrangement (19) can be used to control the flow rate of the amount of fluid flowing in the at least one microfluidic channel (13).

Description

[0001] The invention relates to a biotechnological analysis module for analyzing a sample and a biotechnological analysis system.

[0002] Monitoring reactors and bioreactors is of paramount importance in the production of chemical substances, biopharmaceuticals, and the development and testing of active pharmaceutical ingredients. Continuous, real-time monitoring of as many process-relevant parameters as possible is advantageous for maximizing yield and product quality while reducing development and production costs. While batch reactors—that is, reactions within a closed vessel and a reaction volume—are predominantly used in the production of chemical substances and biopharmaceuticals, novel bioreactors, such as so-called "organ-on-a-chip" systems, are employed, particularly in drug development. These systems replicate the functions of individual or multiple organs and possess greater physiological relevance.

[0003] Electrical, chemical, biochemical, electrochemical, and / or optical measurement methods are used to monitor these reactors. The aim is to monitor reaction conditions, reactants and products, as well as cell-, tissue-, and organ-specific parameters. Many important parameters are often monitored "offline," meaning by taking samples and analyzing them using measurement equipment located separately from the reactor. However, taking samples removes volume from the reactor, which can disrupt sensitive reaction equilibria. Especially in smaller reactors with reaction volumes in the micro- to milliliter range, sampling is therefore severely limited or even impossible, and continuous process monitoring is not feasible. However, monitoring particularly small reactors is essential for the cost-effective development of new processes and test systems in the form of highly parallelized screening systems.

[0004] The task is therefore to provide an easily scalable and cost-effective system with which biochemical reactions can be carried out and samples can be analyzed very easily.

[0005] The problem is solved by a biotechnological analysis module for analyzing a sample according to independent claim 1 and by a biotechnological analysis system according to claim 26. Advantageous embodiments of the biotechnological analysis module are specified in claims 2 to 25. Claims 27 to 32 contain embodiments of the biotechnological analysis system.

[0006] This invention presents, in particular, a solution for easily scalable, controlled, and monitored biotechnological reactions using small sample volumes. The described arrangement also enables continuous analysis of reaction reactants or products in the reactor or an associated sample volume using electrical, electrochemical, and / or optical measurement methods through the integration of the necessary measurement connections. The improved scalability, smaller sample volumes, and reduced need for external laboratory equipment allow biotechnological reactions, processes, and / or analyses to be performed more quickly and cost-effectively.

[0007] The biotechnological analysis module according to the invention comprises a reactor and a system consisting of a microfluidic system and a photonic circuit, and is particularly suitable for the analysis of a sample. The reactor preferably serves to carry out chemical, biochemical reactions and / or biotechnological processes. Preferably, the sample to be analyzed is taken from the reactor in order to monitor the processes within the reactor.

[0008] The photonic circuit has a surface oriented towards the sample being analyzed. A first part of the surface can be brought into contact with the sample. A second part of the surface, separated from the first part, is connected to the microfluidic system. In other words, the microfluidic system is arranged on the surface of the photonic circuit and connected to it as a single unit. There is not direct contact between the photonic circuit and the microfluidic system across the entire surface of the photonic circuit. Rather, spaces (including cavities) can be formed between the photonic circuit and the microfluidic system within the assembly.

[0009] The first part of the photonic circuit's surface encloses a sample volume with the microfluidic system. This (cavity) thus formed is connected to the reactor, allowing the sample to be introduced from the reactor into the sample volume.

[0010] The microfluidic system comprises at least one microfluidic channel connected to the sample volume and / or the reactor. If the microfluidic channel is connected to the sample volume, a fluid is supplied to and / or discharged from the sample volume through this channel. If the microfluidic channel is connected to the reactor, a fluid is supplied to and / or discharged from the reactor through this channel. If the microfluidic channel is connected to both the reactor and the sample volume, fluid exchange can occur between the reactor and the sample volume via the microfluidic channel, allowing, in particular, the sample to be extracted from the reactor and transferred to the sample volume.

[0011] The photonic circuit includes an optical waveguide assembly. The optical waveguide assembly comprises one or more optical waveguides.

[0012] The optical waveguide arrangement is connected to the enclosed sample volume and / or to the at least one microfluidic channel.

[0013] If the optical waveguide assembly is connected to the sample volume, light is coupled from the optical waveguide assembly into the sample volume and / or light from the sample volume into the optical waveguide assembly. Connecting the optical waveguide assembly to the sample volume allows, for example, various spectroscopic measurement techniques to be performed. By coupling light from the optical waveguide assembly into the sample volume, molecules can be specifically excited, and the light coupled from the sample volume into the optical waveguide assembly can be, in particular, fluorescence light.

[0014] If the optical fiber assembly is connected to the at least one microfluidic channel, the light that can be transmitted via the optical fiber assembly is used to control the flow rate through the at least one microfluidic channel. For example, the light can induce local heating of the microfluidic system at the at least one microfluidic channel, thereby changing the cross-sectional area of ​​the at least one microfluidic channel due to thermal expansion. This change in the cross-sectional area of ​​the at least one microfluidic channel alters the flow rate through it.

[0015] In an advantageous further development, the connection between the reactor and the sample volume is realized by a hose connection.

[0016] In an advantageous further development, the connection between the reactor and the sample volume is realized by a pipetting robot. Specifically, a fluid can be extracted from the reactor using the pipetting robot and fed into at least one microfluidic channel of the microfluidic system as the sample to be analyzed. This at least one microfluidic channel is connected to the sample volume.

[0017] In an advantageous further development of the biotechnological analysis module, the reactor comprises a base and at least one wall, thus defining a reactor volume. Optionally, the reactor also includes a cover and / or a membrane designed to allow gas exchange between the reactor volume and its environment.

[0018] In a further advantageous embodiment of the biotechnological analysis module, the base and at least one wall are chemically inert to the fluid. This is particularly advantageous to prevent substances in the reactor volume from attacking the reactor itself.

[0019] In a further advantageous development of the biotechnological analysis module, the reactor includes a membrane designed to allow fluid exchange. The use of a membrane in the reactor for fluid exchange is particularly advantageous for preventing reactor contamination.

[0020] In a beneficial further development of the biotechnological analysis module, the reactor is designed to mix the reactor volume. This mixing can be achieved, for example, by shaking or stirring. It is also conceivable that the mixing could be accomplished by pumping the fluid in a closed loop.

[0021] In a further development of the biotechnological analysis module, the connection between the microfluidic system and the photonic circuit can be detached non-destructively. This is particularly advantageous when the microfluidic system needs to be replaced, as in this case the photonic circuit does not have to be disposed of together with the microfluidic system.

[0022] In a continuing education course within the analysis module, the reactor is a bioreactor. The bioreactor is designed to control and / or monitor biochemical reactions and / or bioprocesses. These biochemical reactions can include, for example, enzymatic catalysis of chemical reactions for molecule synthesis. Furthermore, products can be manufactured in a bioreactor using living organisms, particularly animal cells, plant cells, bacteria, protozoa, and / or fungal cells. The use of cell culture systems for the synthesis of biomolecules such as proteins, or the replication of physiological systems, can also take place in a bioreactor. The replication of physiological systems can be achieved, for example, using adherent cells and / or suspensions.For example, the reactions and / or bioprocesses in the bioreactor can be controlled by changes in temperature or changes in the physiological environment such as the pH value.

[0023] In a further development of the analysis module, the reactor is part of the system comprising the microfluidic system and the photonic circuit. Alternatively, the reactor is arranged at a distance from the system comprising the microfluidic system and the photonic circuit and is connected to the at least one microfluidic channel for fluid exchange between the reactor and the sample volume. The sample to be analyzed can, for example, be extracted from the reactor and introduced into the sample volume via the at least one microfluidic channel. Preferably, after successful analysis using non-destructive measurement methods, the sample can be returned to the reactor to prevent fluid loss and disruption of sensitive reaction equilibria. This is particularly advantageous because small reactors typically utilize only small volumes of less than 1 L, especially less than 100 mL, and particularly less than 10 mL.

[0024] In a further development of the biotechnological analysis module, the sample volume is contained within the lower section of the reactor, which is part of the assembly. The reactor base is formed by at least the first part of the photonic circuit's surface. Optionally, the reactor can also be arranged within the assembly such that part of the reactor base lies above the second part of the photonic circuit's surface. Alternatively, the reactor, which is part of the assembly, can be located on or within the microfluidic system. At least one microfluidic channel connects the reactor to the sample volume for fluid exchange. Positioning the reactor on the surface is particularly advantageous if it is an open reactor. In this case, gas exchange with the surrounding atmosphere can occur.In this case, fluids can also be added to and / or removed from the reactor volume by pipetting. Furthermore, the reactor volume can be advantageously mixed from above by stirring. The arrangement of the reactor within the system is particularly advantageous when a high integration density of reactors is required, as reactors can then be stacked vertically within the system.

[0025] In a continuing education course within the biotechnological analysis module, the photonic circuit comprises one or more of the following materials: silicon, silicon dioxide, GaAs (gallium arsenide), GaAsP (gallium arsenide phosphide), InGaAsP (indium gallium arsenide phosphide), and lithium niobate. The microfluidic system comprises one or more of the following materials: plastic, ceramic, glass-ceramic, and glass. The use of silicon and silicon dioxide as substrates or material systems for the photonic circuit is particularly advantageous because structures that can function as both electrical conductors and optical waveguides can be easily fabricated using established semiconductor manufacturing processes. The use of substrates containing gallium arsenide allows for the application of familiar manufacturing processes for light sources or light detectors, such as photodiodes, thus enabling the cost-effective integration of these elements.The use of plastic for the microfluidic system is particularly advantageous because many biocompatible plastics are now known for use in pharmaceuticals and biotechnology, and these can also be easily molded into specific shapes. This allows, in particular, the fabrication of at least one microfluidic channel with low tolerances. The use of glass or ceramic is especially beneficial because these materials exhibit high resistance to solvents and disinfectants used for cleaning and disinfection in biotechnology.

[0026] In an advantageous further development of the biotechnological analysis module, the microfluidic system is free of semiconductor substrates. In particular, the microfluidic system is free of the semiconductor substrates from which the photonic circuit is formed.

[0027] In an advantageous further development of the biotechnological analysis module, the photonic circuit is free of dielectric printed circuit board materials such as FR4.

[0028] In a further development of the biotechnological analysis module, the second part of the photonic circuit's surface is bonded to the microfluidic system. This bonded connection between the photonic circuit and the microfluidic system cannot be broken non-destructively. This is particularly advantageous because it allows the photonic circuit and the microfluidic system to be manufactured separately using different processes and only later permanently bonded together.

[0029] In a continuing education module of the biotechnological analysis module, the second part of the photonic circuit's surface is bonded to the microfluidic system. Alternatively, the microfluidic system is a 3D-printed part applied to the second part of the photonic circuit's surface using an additive manufacturing process. This additive manufacturing process could, for example, involve 3D printing, where plastic is additively applied to the second part of the photonic circuit's surface, effectively "printing" the microfluidic system onto it. Alternatively, the microfluidic system is an injection-molded part applied to the second part of the photonic circuit's surface using an injection molding process. These methods allow for the formation of a material-bonded connection.

[0030] In a further development of the biotechnological analysis module, a protective layer is provided and applied to the first part of the surface of the photonic circuit to separate the photonic circuit from the sample volume.

[0031] In a further development of the biotechnological analysis module, the protective layer is transparent to the wavelength of light that can be coupled into and / or out of the sample volume by the optical waveguide array. Alternatively or additionally, the protective layer is chemically inert to both the fluid and the sample. This is particularly advantageous when the substrate of the photonic circuit must be isolated from the fluid, but light still needs to be coupled into or out of the sample volume. In particular, this allows for the advantageous separation of aggressive fluids—for example, due to their pH value—from the sensitive substrate. Furthermore, contamination of the sample by detachment of the photonic circuit can be avoided. If, for example, silicon is used as the substrate, a protective layer can be created / applied by oxidizing the surface.The resulting silicon dioxide acts as a protective layer against acids and acidic solutions and is generally safe for food contact, making its use in pharmaceutical manufacturing conceivable. In this case, the protective layer would be formed by silicon dioxide.

[0032] In a continuing education module of biotechnological analysis, the microfluidic system comprises at least one first and one second microfluidic channel, separated by a membrane. This membrane is designed to prevent specific particles and / or molecules from passing from the first microfluidic channel into the second. The principle of reverse osmosis can also be used for this purpose. In this case, the membrane is designed to operate according to the principle of reverse osmosis. Separation occurs, for example, based on particle size, with the membrane pores being permeable to smaller particles while remaining impermeable to larger ones. The first microfluidic channel is the inlet channel, while the second microfluidic channel is the filtrate channel.In certain membrane designs, cross-flow filtration is also possible, where the first microfluidic channel serves as the feed channel for a first substance, but as the filtrate channel for a second substance. In this case, the second microfluidic channel serves as the feed channel for the second substance, and the first microfluidic channel serves as the filtrate channel for the first substance.

[0033] In a further development of the biotechnological analysis module, the microfluidic system comprises at least one storage volume, into which a fluid in the form of a nutrient solution or a reagent solution can be introduced. The at least one storage volume is connected to the reactor and / or the sample volume via the at least one microfluidic channel. The connection of the at least one storage volume to the reactor is particularly advantageous, as it allows nutrients to be added to the reactor. The nutrient solution can be, for example, a glucose solution. However, fluids containing dissolved amino acids, lipids, or other macromolecules are also conceivable as nutrient solutions. In one embodiment, a plurality of storage volumes can be provided, each filled with different nutrient solutions.The reagent solution can consist of acids or bases, for example, which are used to adjust the pH of the reactor volume. Connecting at least one storage volume to the sample volume is particularly advantageous when reagents are required for sample analysis, such as to initiate a detection reaction. The nutrient and reagent solutions can flow within the microfluidic system by gravity and / or capillary action.

[0034] In a further development of the biotechnological analysis module, the microfluidic system comprises a valve unit with at least one first valve, wherein the at least one first valve is arranged in the at least one microfluidic channel. The at least one first valve is configured to control the flow through the at least one microfluidic channel. This is particularly advantageous for controlling fluid movements within the microfluidic system. In one embodiment, the at least one first valve in the at least one microfluidic channel connecting the reactor and the sample volume can be used to initiate sample extraction from the reactor by opening the at least one first valve. In another embodiment, the at least one first valve in the at least one microfluidic channel connecting the at least one storage volume to the reactor can control the inflow of nutrients.

[0035] In a further development, the valve unit includes a pneumatic control inlet. This pneumatic control inlet is designed to be subjected to either positive or negative pressure. The flow rate through the at least one microfluidic channel is adjustable depending on the applied pressure. For example, positive pressure at the pneumatic control inlet can reduce the flow rate through the at least one microfluidic channel by forcing a diaphragm into the channel, thus reducing its cross-section.

[0036] In a further development of the biotechnological analysis module, the valve unit includes a control input, which is connected to at least one control optical waveguide of the photonic circuit's optical waveguide arrangement or to an electrical control line of the photonic circuit. The flow rate through the at least one microfluidic channel is adjustable depending on the control signal applied to the control input. For example, with an optical control input, the flow rate through the at least one microfluidic channel can decrease with increasing light power at the control input. It is also conceivable that by using specific light wavelengths and focusing the applied light power at the control input within the at least one microfluidic channel, the flow rate of certain particles dissolved in the fluid through the at least one microfluidic channel can be prevented by optical dipole forces.

[0037] In a further development of the biotechnological analysis module, the at least one first valve is formed by a section of the at least one microfluidic channel. The cross-section of this section of the at least one microfluidic channel can be varied depending on the applied light power from the at least one first control optical waveguide or the electrical power at the control input. In one embodiment, the applied light power can locally heat the section of the at least one microfluidic channel. This heating causes the wall of the microfluidic system to expand, thus changing the cross-section of the at least one microfluidic channel at that point. In another embodiment, the local heating can be caused by an electric current.In another embodiment, the electrical power at the control input can be used via piezoelectric elements in the section of at least one microfluidic channel to change the cross-section.

[0038] In a further development of the biotechnological analysis module, the valve unit comprises at least a second valve, which is arranged in the at least one microfluidic channel adjacent to the at least one first valve. By alternately switching the first and second valves, a directed transport of the fluid in the at least one microfluidic channel can be generated. This directed transport of the fluid in the at least one microfluidic channel is possible in a first direction as well as in a second direction opposite to the first. Like the at least one first valve, the at least one second valve has a control input, which differs from that of the at least one first valve. For example, a second control optical waveguide can be provided.Preferably, the at least one first valve and the at least one second valve are both controlled by overpressure or underpressure, by light intensity, or both by electrical light intensity at their respective control inputs. This is particularly advantageous for implementing pumps in the microfluidic system with simple valves. In one embodiment, such a valve unit can be arranged in the at least one microfluidic channel that connects the reactor and the sample volume. This allows, for example, a sample to be taken from the reactor and, after non-destructive analysis, pumped back into the reactor from the sample volume, so that sensitive reaction equilibria are not disturbed and no volume is lost from the reactor.In another embodiment, such a valve unit can be arranged in the at least one microfluidic channel that connects the at least one storage volume to the reactor. This allows, for example, nutrient solutions to be selectively supplied to the reactor.

[0039] In a further development of the biotechnological analysis module, an optical coupler unit is provided with an optical input port, an optical output port, and an optical bidirectional port. The optical waveguide assembly includes a first optical waveguide. The first end of the first optical waveguide is connected to the optical bidirectional input port, and the second end is connected to the sample volume. The optical coupler unit is configured to output light supplied to the optical coupler unit at the optical input port at the optical bidirectional port, and to output light emitted from the sample volume, supplied to the optical coupler unit at the optical bidirectional port, at the optical output port.The light output can be via a light guide, which may, for example, have an optical connector such as those known from the telecommunications industry. The optical coupler unit can be implemented, for example, by planar coupler structures in a photonic circuit. Preferably, the coupling strength depends on the propagation direction of the light. The optical coupler unit can, for example, be implemented by an (optical) power divider combined with an optical diode. The optical diode is located at the optical input and / or the optical output terminal.

[0040] In an advantageous further development of the biotechnological analysis module, the selectivity of the optical coupler unit is based on the polarization of the light. For example, light of a specific polarization direction, which can be supplied to the optical, bidirectional port, is output at the optical output port. Light with this polarization direction that can be supplied to the optical, bidirectional port cannot be output at the optical input port.

[0041] In an advanced version of the biotechnological analysis module, the optical coupler unit is configured to output light supplied to the optical, bidirectional port at the optical output port, depending on its wavelength. Specifically, the selectivity of the optical coupler unit is achieved through optical filters at the optical input and / or output ports, which transmit only light of specific wavelengths. This is particularly advantageous when the light supplied to the optical input port and the light supplied to the optical, bidirectional port have different wavelengths. This is utilized, for example, in fluorescence spectroscopy. The light used to excite the sample, with a first wavelength, is supplied to the optical coupler unit at the optical input port and then directed to the sample within the sample volume via the optical, bidirectional port of the optical coupler unit.The fluorescence light emitted by the sample within the sample volume, with a second wavelength different from the first, is received at the optical, bidirectional port and output at the optical output port.

[0042] In a continuing education module of biotechnological analysis, the optical waveguide arrangement comprises a first and a second optical waveguide. The first optical waveguide is configured to couple light into the sample volume. The second optical waveguide is configured to receive light from the sample volume. The first and second optical waveguides are arranged such that a line-of-sight connection exists between them through the sample volume. Alternatively, the second optical waveguide is arranged outside of a line-of-sight connection through the sample volume to the first optical waveguide. A line-of-sight connection describes a situation where light can propagate directly along the line of communication. The line-of-sight connection can also be created by inserted optical elements, such as mirrors.In this case, the direction of light propagation along the arrangement is determined according to the laws of (geometric) optics. This determined line is the line-of-sight connection. Arranging the first and second optical waveguides such that a line-of-sight connection exists between them is particularly advantageous when performing transmission measurements. For example, the optical density of the sample can be determined using the Lambert-Beer law via a transmission measurement. The determined optical density is used to measure the concentration of an analyte in a solution. For example, nutrient or cell concentrations in the sample volume can be determined in this way.Positioning the second optical waveguide outside the line-of-sight connection through the sample volume to the first optical waveguide is particularly advantageous when low-intensity light is emitted from the sample volume and received by the second optical waveguide. The absence of the line-of-sight connection prevents the light coupled into the sample volume from the first optical waveguide from being directly coupled into the second optical waveguide, thus improving the signal-to-noise ratio of, for example, scattered light measurements. Scattered light measurements include, in particular, Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS), reflection measurements, and fluorescence measurements.

[0043] A temperature control element is included in a further development module of the biotechnological analysis module. This element is designed to regulate the temperature of the sample within the sample volume and / or a fluid within the reactor. A temperature control element is particularly useful because many reactions and reaction equilibria are temperature-dependent. For example, the temperature control element can also be used to regulate time-varying temperature profiles. The temperature control element includes, for instance, a heating resistor. This resistor can be advantageously positioned on or within the photonic circuit. Alternatively or additionally, the use of a Peltier element is provided, which also enables cooling.In addition to an actuating element such as a heating resistor and / or a Peltier element, the temperature control element advantageously comprises a temperature sensor and a controller to adjust the temperature of the sample in the sample volume or of the fluid in the reactor to a predetermined setpoint using the actuating element. A temperature-dependent resistor, such as a standardized PT100 or PT1000 element, is particularly suitable as a temperature sensor. P or PI controllers are preferably used as the controller.

[0044] In a further development of the biotechnological analysis module, the temperature control unit is specifically designed to adjust the bioreactor temperature to a physiological temperature. This is particularly advantageous, for example, when using biological processes such as enzymatic reactions, as these exhibit optimal reaction rates primarily within physiological temperature ranges. Specifically, this physiological temperature range extends from +20°C to +50°C, particularly from +25°C to +45°C, and especially from +35°C to +40°C.

[0045] In a further development of the biotechnological analysis module, the photonic circuit comprises at least one light source, which is configured to generate the light and couple it into the optical waveguide assembly. Alternatively or additionally, the photonic circuit comprises at least one photodetector, which is connected to the optical waveguide assembly. The photodetector is configured to convert the light coupled into the optical waveguide assembly into an electrical signal. The light source is preferably in the form of a laser or a light-emitting diode (LED). The integration of the light source into the photonic circuit and its direct connection to the optical waveguide assembly are particularly advantageous because, for the user of the biotechnological analysis module, the need to connect an external light source eliminates the need for manual operation.The photodetector is preferably implemented in the form of a photodiode. Light power can be determined very easily using a photodetector integrated into the photonic circuit. For example, many spectroscopy methods for identifying specific molecules require the measurement of light power using a photodetector. The photodetector can be combined with a wavelength-dependent element to determine the light power at specific spectral components. Lasers and / or LEDs as well as photodiodes can be easily fabricated in semiconductor substrates such as GaAs, InGaAs, or InGaAsP using known manufacturing processes. For spectroscopic applications, the light source can be implemented as a frequency-stabilized laser. Various resonators can be incorporated into the light source for frequency stabilization. In particular, the light source can be monofrequency and tunable, i.e.,The wavelength of the emitted light can be variable. A laser diode design is particularly advantageous, as the emitted wavelength can be varied by current and temperature. The wavelength-dependent element can, for example, be in the form of a grating and / or filter.

[0046] In a further development of the biotechnological analysis module, the photonic circuit comprises an electronic measuring unit in the form of an electrical sensor and / or an electrochemical sensor and / or an electrode. The electrical measuring unit is arranged on the first part of the surface of the photonic circuit so that it can be brought into physical contact with the sample within the sample volume. In one embodiment, the electrical sensor can, for example, be implemented as a temperature-dependent resistor, allowing the temperature of the fluid in the sample volume to be determined. The use of standardized PT100 or PT1000 elements is particularly advantageous for this purpose. In another embodiment, the electrical resistance or electrical conductivity of the fluid in the sample volume can be determined by the electrical sensor.Conductivity, for example, provides information about the ion concentration, cell concentration, or pH value. In another embodiment, the electrical sensor can be used to measure capacitance. The measured electrical capacitance provides information about the live cell concentration, for example. In a further embodiment, the electrochemical sensor can include a detection element. The detection element is designed to bind a specific analyte and output an electrical signal depending on the binding state. The binding state describes whether an analyte is bound and, optionally, how many analytes are bound. This also enables, in particular, concentration measurements of analytes. The detection element can, for example, include antibodies, aptamers, and / or polymers.

[0047] In a further development module of the biotechnological analysis module, the photonic circuit includes an analog-to-digital converter (ADC). The ADC is designed to convert a measurement signal from the electrical measuring unit and / or the electrical signal from the photodetector into a digital signal. Converting analog measurement signals into digital signals is particularly advantageous when the measurement data is processed and recorded by a central control unit. For example, the digitized data can be archived for quality assurance purposes, enabling the tracking of processes after the synthesis of reaction products in the reactor. For this purpose, the central control unit can include a computer or another suitable storage device.

[0048] In a further training module of the biotechnological analysis module, the optical waveguide arrangement comprises an optical multiplexer unit and / or an optical demultiplexer unit. The optical multiplexer unit is configured to split the light from one optical waveguide into several outgoing optical waveguides and optionally to adjust the intensity of the light in the multiple outgoing optical waveguides. Alternatively or additionally, the optical demultiplexer unit is configured to combine the light from several incoming optical waveguides into a single outgoing optical waveguide and / or to transmit the light from at least one optical waveguide from several incoming optical waveguides, but not from all of them, into the single outgoing optical waveguide.The use of an optical multiplexer unit is particularly advantageous because, in this case, the optical wave array of the biotechnological analysis module only requires one connection for coupling in light from a single light source. The light can be coupled out and used at the multiple outgoing optical waveguides without the need for multiple light sources. The light power in each of the multiple outgoing optical waveguides can be switched on or off, for example, via an optical switch. The single optical waveguide can be distributed evenly or at specific intensity ratios to the multiple outgoing optical waveguides using a power divider. The light at the multiple outgoing optical waveguides can, for example, be used to actuate the valves of the valve unit to create a pumping action.The optical demultiplexer unit can, for example, be implemented as a combiner. The use of optical switches in the multiple incoming optical fibers is particularly advantageous for directing only light from individual incoming optical fibers to the individual outgoing optical fiber. In one embodiment, the optical demultiplexer unit can be used to direct the light from various fluorescence measurements to a single outgoing optical fiber connected to a spectrometer. In this case, the demultiplexer unit is configured to sequentially direct the light from the various individual incoming optical fibers to the single outgoing optical fiber and the spectrometer connected to it.

[0049] An interface unit is provided in an advanced version of the biotechnological analysis module. The interface unit is designed to receive light from outside the biotechnological analysis module and couple it into the optical fiber assembly, and / or to receive light from the optical fiber assembly and transmit it outside the biotechnological analysis module. Alternatively or additionally, the interface unit is designed to receive fluids from outside the biotechnological analysis module and direct them into the at least one microfluidic channel, and / or to receive fluids via the at least one microfluidic channel and direct them outside the biotechnological analysis module.Alternatively or additionally, the interface unit is designed to receive electrical signals from outside the biotechnological analysis module and transmit them to the photonic circuit, and / or to receive electrical signals from the photonic circuit and transmit them outside the biotechnological analysis module. For example, the interface unit can be configured as an optical and / or electrical connector system. In particular, the use of PC / FC or PC / APC connections for optical fibers is advantageous because these can be manufactured industrially at low cost. A particular advantage in this case is that optical signals from the photonic circuit in the biotechnological analysis module can be transmitted directly to external analytical instruments, such as a fiber-coupled spectrometer, via optical fibers without the need for complex adjustments.For example, an interface unit with a fiber optic connection can be advantageously used to easily guide light from an external fiber laser to the photonic circuit of the biotechnological analysis module and couple it into the optical fiber array. Electrical signals received by the photonic circuit and transmitted externally can include analog signals such as voltages and / or photodiode currents, and / or digital signals such as output signals from ADCs. Electrical signals received externally and fed to the photonic circuit can include, in particular, power and voltage supplies used to operate sensors, valves, lasers, and / or photodiodes. These electrical signals can also include digital signals used to adjust valve controls or other operating parameters of the biotechnological analysis module.The interface unit can, for example, be configured to receive nutrient solutions from an external source and convey them to the reactor and / or storage volume via at least one microfluidic channel. The interface unit is particularly advantageous if it can receive reaction products from the reactor via at least one microfluidic channel and convey them externally. In this case, the interface unit can be used, for example, to extract synthesized molecules from the fluid. The interface unit can also be specifically configured to receive fluids from the reactor and convey them to the sample volume.

[0050] In an advantageous further development of the biotechnological analysis module, the interface unit is designed to receive gases from outside the biotechnological analysis module and direct them to the reactor.

[0051] In a further advantageous development of the biotechnological analysis module, the interface unit includes a pneumatic control connection. This pneumatic control connection is designed to be subjected to positive or negative pressure from outside the biotechnological analysis module and to transmit this pressure to the pneumatic control input of the valve unit.

[0052] In an advantageous further development of the biotechnological analysis module, the optical waveguide arrangement of the photonic circuit is free of superimposed layers of solder mask.

[0053] The biotechnological analysis system according to the invention comprises a first and at least one second biotechnological analysis module according to the invention. Furthermore, a common carrier module is provided, wherein the first and the at least one second biotechnological analysis module are arranged on the common carrier module. A central control and / or evaluation device is provided. The central control and / or evaluation device is configured to receive first measurement signals for the sample to be analyzed from the first biotechnological analysis module and second measurement signals for the sample to be analyzed from the at least one second biotechnological analysis module. The arrangement of the first biotechnological analysis module and the at least one second biotechnological analysis module on a common carrier module is particularly advantageous for facilitating the scalability of the system while maintaining a compact design.The central control and / or evaluation unit can be implemented, for example, as a computer, a microcontroller, and / or an FPGA with a memory unit. Combinations of these implementation options are also conceivable. The measurement signals can advantageously be transmitted to the central control and / or evaluation unit via the interface unit. Both analog and digital signals can be transmitted. For example, analog signals can be acquired, digitized, and stored by the central control and / or evaluation unit. It is also conceivable that an ADC in the biotechnological analysis module digitizes measurement signals and transmits them as digital data via the interface unit to the central control and / or evaluation unit, where they are received and processed.

[0054] In an advantageous further development of the biotechnological analysis system, the central control and / or evaluation device is configured to further process received measurement signals, store received measurement signals, determine operating parameters for the individual biotechnological analysis modules based on received measurement signals and transmit them to these modules, and / or correlate various received measurement signals with one another. For example, the central control and / or evaluation device can receive measurement signals containing information about temperature and then adjust the temperature control element to increase or decrease the temperature. The received measurement signals can also contain information about nutrient content.In this case, the central control and / or evaluation device can, for example, be designed to control the biotechnological analysis module in such a way that nutrients are supplied to the reactor from the storage volume when a minimum nutrient content is undershot.

[0055] In a further development of the biotechnological analysis system, at least one microfluidic channel of the first biotechnological analysis module is connected to at least one microfluidic channel of at least one second biotechnological analysis module, thus enabling fluid exchange between the reactor of the first biotechnological analysis module and the reactor of the second biotechnological analysis module. This connection can be established via the carrier module or directly between the first analysis module and the second biotechnological analysis module. Connecting the first and second biotechnological analysis modules via their respective microfluidic channels is advantageous, for example, when the biotechnological analysis system simulates a physiological reaction chain or a reaction cycle.Here, a first reaction step is carried out in the first biotechnological analysis module. In at least one second biotechnological analysis module, the reaction product from the reactor of the first biotechnological analysis module is transferred to the reactor of the second biotechnological analysis module via at least one microfluidic channel. There, it serves as the reactant for a second reaction step. Such an implementation is particularly advantageous for building "organ-on-a-chip" systems. For example, metabolic processes of pharmaceutical substances can be simulated along various organs such as the liver and kidneys, thereby saving costs in the development and testing of pharmaceuticals.

[0056] In a further development of the biotechnological analysis system, the first biotechnological analysis module is attached to the carrier module via a detachable plug-in and / or snap-in connection and / or magnetic connection. At least one second biotechnological analysis module is also attached to the carrier module via a detachable plug-in and / or snap-in connection and / or magnetic connection. The use of a detachable connection is particularly advantageous because it allows the biotechnological analysis module to be removed from the carrier module, especially after successful measurement or completion of the synthesis in the reactor, and a new biotechnological analysis module to be inserted. This is particularly advantageous if, for reasons of purity, the biotechnological analysis modules must first undergo extensive cleaning and / or sterilization after use, or are disposed of as single-use products.

[0057] In a further development of the biotechnological analysis system, at least one second biotechnological analysis module can be removed from the carrier module without interrupting the operation of the first biotechnological analysis module. The ability to replace a single biotechnological analysis module without interrupting the operation of other biotechnological analysis modules within the biotechnological analysis system is particularly advantageous for achieving maximum operational capability. This reduces operating costs, especially in automated operation.

[0058] In a further development of the biotechnological analysis system, a light source is provided. The light source is connected to an optical fiber array in the carrier module, wherein the optical fiber array of the carrier module is configured to transmit light from the light source sequentially or in parallel to the optical fiber arrays of the first and at least one second biotechnological analysis module. Alternatively, the light source is connected to the optical fiber array of the first biotechnological analysis module. The optical fiber array is configured to forward the light received from the light source to the optical fiber array of the respective adjacent, at least one second, biotechnological analysis module.

[0059] A spectrometer is provided in a further development of the biotechnological analysis system. The spectrometer is connected to an optical fiber array in the carrier module. This optical fiber array is configured to receive light from the optical fiber array of the first biotechnological analysis module and from at least one second biotechnological analysis module and to transmit it sequentially to the spectrometer. Advantageously, optical fibers with standard connectors from the telecommunications industry can be used to connect the light source to the optical fiber array of the carrier module, resulting in particularly low manufacturing costs.

[0060] In a further advantageous development of the biotechnological analysis system, a spectrometer is provided. The spectrometer is connected to an optical fiber array in the carrier module. This optical fiber array is configured to receive light from the optical fiber array of the first biotechnological analysis module and from at least one second biotechnological analysis module and transmit it in parallel to the spectrometer. Parallel transmission is advantageous when a large number of samples are being analyzed, for which a negative result is expected. If a positive result is detected in the sample analyzed in parallel, the samples can subsequently be analyzed individually (sequentially) to determine which sample is positive. Parallel analysis saves costs when the probability of a positive result is very low.This is the case, for example, when monitoring reactions to unwanted impurities in the reactor.

[0061] In a further development of the biotechnological analysis system, the first biotechnological analysis module and at least one second biotechnological analysis module include an interface unit. The carrier module has an interface unit corresponding to the respective interface unit of the biotechnological analysis module. If the carrier module includes an interface unit, this is particularly advantageous for enabling the easy exchange of the biotechnological analysis modules.

[0062] In an advantageous further development of the biotechnological analysis module, it is designed in a standardized size, particularly in the form of a microtiter plate or a cell culture plate. This allows for easy integration of the biotechnological analysis module into systems with existing infrastructure. In particular, the use of pipetting robots or microscopes is greatly facilitated. Scalability of a biotechnological analysis system according to the invention is also simplified when the biotechnological analysis module is designed in a standard form.

[0063] In an advantageous advanced training, the biotechnological analysis system comprises more than 2, 4, 8, 16, 32, 64, 128, 256 or more than 512 biotechnological analysis modules.

[0064] The invention is described below by way of example only, with reference to the drawings. The drawings show: Fig. 1: an embodiment of a biotechnological analysis module according to the invention with a spaced-apart reactor; Fig. 2: an embodiment of a biotechnological analysis module according to the invention with a reactor, wherein the reactor is part of the assembly; Fig. 3: a microfluidic system with a first and a second microfluidic channel and a membrane; Fig. 4: a valve unit with several valves; Fig. 5: a spectroscopy unit with an optical coupler; Fig. 6: a spectroscope with an integrated light source; and Fig. 7: an embodiment of a biotechnological analysis system according to the invention.

[0065] Fig. Figure 1 shows an embodiment of the biotechnological analysis module 1 according to the invention, comprising a spaced-apart reactor 2. A reactor volume 3 of the reactor 2 is enclosed by a reactor base 4 and at least one reactor wall 5. The reactor 2 also includes a mixing device 6, which is designed to mix the reactor volume 3. This device may be a stirring rod 7. The reactor 2 also includes a reactor cover 8 in which a membrane 9 is embedded. Gas and / or fluid exchange is possible through the membrane 9. For example, oxygen, nitrogen, and / or carbon dioxide can be supplied to the reactor 2 through the membrane 9. It is also conceivable that gases can escape from the reactor 2 through the membrane 9 to prevent the formation of overpressure in the reactor 2.

[0066] A system 10 consisting of a microfluidic system 11 and a photonic circuit 12 comprises at least one microfluidic channel 13 and a sample volume 14. The sample to be analyzed from reactor 2 can be introduced into the sample volume 14 via a first connection 15 from reactor 2 to sample volume 14. In the illustrated embodiment, the analyzed sample can be returned to reactor 2 via a second connection 16. The first connection 15 from reactor 2 to sample volume 14 and the second connection 16 can be part of an interface unit 33 (see Fig. 7, or in Fig. 1 designated as interface unit (fluidic connection) 33c).

[0067] At least one microfluidic channel 13 is arranged on the sample volume 14, so that an inflow and / or outflow of a fluid is possible.

[0068] The photonic circuit 12 has a surface oriented towards the sample to be analyzed, wherein a first part 70 of the surface can be brought into contact with the sample to be analyzed, thereby limiting the sample volume 14 on one side. Furthermore, a second part 71 of the surface is connected to the microfluidic system 11.

[0069] In the illustrated embodiment, fluid exchange with the reactor 2 is enabled via the at least one microfluidic channel 13. A particular advantage is that the sample to be analyzed can be fed from the reactor 2 to the sample volume 14 via the at least one microfluidic channel 13, and the analyzed sample can also be fed back to the reactor 2 via the microfluidic channel 13. This ensures that sensitive reaction equilibria in the reactor 2 are not disturbed and the volume of the fluid contained in the reactor 2 is maintained.

[0070] In the embodiment shown here, the at least one microfluidic channel 13 is free of a pump. The sample to be analyzed is taken from the reactor volume 3, for example by means of a pipetting robot, and then flows through the at least one microfluidic channel 13 to the sample volume 14 by means of gravitational and / or capillary forces.

[0071] It is also conceivable that a sample is taken from reactor 2 using a pump (not shown). This pump can be located outside the microfluidic system 11, but within the first connection 15 of reactor 2 to the sample volume 14. Alternatively, the pump can be part of the microfluidic system 11 and, in particular, be located in the at least one microfluidic channel 13.

[0072] The sample volume 14 is separated from the substrate 18 of the photonic circuit 12 by a protective layer 17. The protective layer 17 is transparent to both the light coupled into the sample volume 14 via an optical waveguide arrangement 19 and the light coupled out of the sample volume 14. The protective layer 17 can also be chemically inert with respect to the sample. This prevents detachment from the substrate 18 of the photonic circuit 12 and contamination of the sample volume 14. If the substrate 18 consists of silicon, for example, the protective layer 17 can be produced by oxidizing the substrate 18 to silicon dioxide. Silicon dioxide is transparent to many wavelengths and also inert to many solutions.

[0073] Optical connections are shown with dashed lines in the figures. In the illustrated embodiment, the optical waveguide arrangement 19 comprises a first optical waveguide 20 and a second optical waveguide 21. The first optical waveguide 20 is configured to couple the light, which is coupled into the sample volume 14 at its first end via the input port 22. The second optical waveguide 21 is configured to couple the light, which is coupled into the sample volume 14, at its second end via the output port 23. The input port 22 and the output port 23 can be part of the interface unit 33 (see Fig. 7, or in Fig. 1 designated as interface unit (optical connection) 33a).

[0074] For example, light can be coupled into the sample volume 14 via the first optical waveguide 20, exciting molecules in the sample volume 14. Fluorescence light produced by the de-excitation of the molecules is coupled into the second optical waveguide 21 and output at the output terminal 23. The output light can be connected to a spectrometer 57 (see Fig. 5 and Fig. 7) are transferred and analyzed there. The molecules can be uniquely identified by their characteristic spectral distribution.

[0075] An electrical measuring unit 24 is provided. The electrical measuring unit 24 is arranged on a first part 70 of the surface of the photonic circuit 12 such that the electrical measuring unit 24 can be brought into physical contact with the sample in the sample volume 14. The electrical measuring unit 24 is connected to an electrical output terminal 26 via an electrical line 25. The electrical output terminal 26 can be part of the interface unit 33 (see Fig. 7, or in Fig. 1 designated as interface unit (electrical connection) 33b).

[0076] The electrical measuring unit 24 could, for example, be a temperature sensor. This could be, in particular, in the form of a PT100 or a PT1000 element.

[0077] The microfluidic system 11 comprises a storage volume 27 containing a nutrient or reagent solution 28. The storage volume 27 is connected to the sample volume 14 via at least one microfluidic channel 13. A valve unit 29 is provided in the section of the microfluidic channel 13 that connects the storage volume 27 to the sample volume 14. The valve unit 29 is configured to adjust the flow rate of the nutrient or reagent solution 28 from the storage volume 27 into the sample volume 14 as a function of a control signal applied to the control input 30. In this example, the control signal is an electrical signal supplied to the control input 30 via an electrical control line 31. The electrical control line 31 receives the electrical control signal at an electrical control terminal 32. The electrical control terminal 32 can be part of the interface unit 33 (see Fig. 7, or in Fig. 1 designated as interface unit (electrical connection) 33b).

[0078] In the Fig. In the embodiment shown in Figure 1, the storage volume 27 preferably comprises a reagent solution 28, which can be supplied to the sample volume 14 via the at least one microfluidic channel 13. The supply of the reagents allows specific detection reactions to be generated in the sample volume 14. The reaction products of these detection reactions can then be detected, for example, by spectroscopic methods. For instance, Raman spectroscopy can be used for this purpose. In this case, light of a first wavelength would be coupled into the sample volume 14 via the first optical waveguide 20. The emitted light of a second wavelength is coupled into the second optical waveguide 21 and measured by means of a spectrometer 57 (see Figure 1). Fig. 5 and Fig. 7) analyzed. Typically, the emitted light is lower energy, meaning it has a longer wavelength than the light used for excitation. The emitted light is characteristic of certain molecules, which is why these can be identified based on the spectral distribution of the emitted light.

[0079] It is also conceivable that the storage volume 27 comprises a nutrient solution 28, which can be supplied to the reactor volume 3 via at least one microfluidic channel 13 and the second connection 16. The nutrient solution 28 could, in particular, be a glucose-containing solution used to supply bacteria or other animal cells with energy.

[0080] In the embodiment shown here, the nutrient or reagent solution 28 flows by gravity from the storage volume 27 through the at least one microfluidic channel 13 into the sample volume 14. Accordingly, the valve unit 29 preferably comprises only a single valve 41 (see Fig. 4) Alternatively or additionally, the valve unit 29 can also be configured to produce a directed pumping action by alternately switching several valves 41, 42, 43 (see Fig. 4) to achieve.

[0081] The Fig. Figure 2 shows a further embodiment of the biotechnological analysis module 1 according to the invention. In contrast to the embodiment shown in Figure 2, the following embodiment is shown in Figure 2: Fig. 1 is in Fig. 2 the reactor 2 is not spaced apart from the assembly 10 consisting of the microfluidic system 11 and the photonic circuit 12, but is part of the assembly 10.

[0082] A lower part of reactor 2 comprises sample volume 14. In other words, sample volume 14 is a part of reactor volume 3.

[0083] It is also conceivable that reactor 2 is part of the assembly 10, but sample volume 14 is not part of reactor volume 3. In such an embodiment, reactor 2 would, for example, be arranged on the surface of the microfluidic system 11. The at least one microfluidic channel 13 would connect reactor 2 to sample volume 14 for fluid exchange.

[0084] In the Fig. In the embodiment shown in Figure 2, at least one microfluidic channel 13 is arranged on the reactor 2. Nutrient or reagent solutions 28, for example, can be supplied through the at least one microfluidic channel 13 from a storage volume 27 (in Fig. (2 not shown) can be supplied to reactor 2. A fluid can also be withdrawn from reactor 2 through at least one microfluidic channel 13. The withdrawn fluid can, for example, be supplied to another sample volume 14. This is particularly advantageous if the withdrawn fluid is to be analyzed without the influence of the reaction dynamics in reactor 2. The arrangement of the sample volume 14 as part of the reactor volume 3 is particularly advantageous to ensure continuous monitoring of the reaction dynamics (in-situ measurement) in reactor 2. A combination of the two aforementioned possibilities is conceivable.

[0085] The assembly 10 includes a temperature control element 34, which is designed to adjust the temperature in the sample volume 14 and / or the fluid in the reactor 2. The temperature control element 34 can be, for example, a heating resistor or a Peltier element. The temperature can be adjusted by applying an electric current. The electric current can be applied to an electrical temperature control input 35 and is supplied to the temperature control element 34 via an electrical supply line 36.

[0086] The use of the temperature control element 34 is particularly advantageous when the temperature of the sample and / or the fluid in the reactor 2 is controlled by the electrical measuring unit 24 (in Fig. (2 not shown) is determined and the current applied to the electrical temperature control input 35 is adjusted by means of a controller so that the temperature of the sample and / or the fluid in reactor 2 corresponds to a predetermined setpoint. P or PI controllers are preferably used as controllers.

[0087] The Fig. Figure 3 shows an embodiment of the biotechnological analysis module 1, wherein the microfluidic system 11 comprises at least a first microfluidic channel 37 and a second microfluidic channel 38. The first microfluidic channel 37 and the second microfluidic channel 38 are separated from each other by a membrane 39. The membrane 39 is designed to prevent, for example, certain particles and / or molecules, from passing from the first microfluidic channel 37 into the second microfluidic channel 38, for example, by reverse osmosis.

[0088] The second microfluidic channel 38 is connected to the sample volume 14 via at least one microfluidic channel 13.

[0089] The assembly 10 comprises the microfluidic system 11 and the photonic circuit 12. The photonic circuit 12 includes the substrate 18. The substrate 18 can be, for example, silicon or gallium arsenide. The substrate 18 can also consist of silicon or gallium arsenide.

[0090] The photonic circuit 12 comprises an optical waveguide arrangement 19 with a first optical waveguide 20 and a second optical waveguide 21. The first optical waveguide 20 is connected at one end to the input terminal 22 and at its second end is arranged at the sample volume 14 such that light from the first optical waveguide 20 can be coupled into the sample volume 14.

[0091] The second optical waveguide 21 is arranged on the sample volume 14 such that light from the sample volume 14 can be coupled into the second optical waveguide 21. The coupled-in light can be output at the output terminal 23.

[0092] The input port 22 and the output port 23 can be part of the interface unit 33 (see Fig. 7) be, in particular part of the interface unit (optical connector) 33a. The interface unit (optical connector) 33a may, for example, be a fiber optic connector from the telecommunications industry.

[0093] The photonic circuit 12 and the sample volume 14 are separated from each other by a protective layer 17. The protective layer 17 is transparent to the wavelengths of light that are coupled into the sample volume 14 via the first optical waveguide 20 and coupled from the sample volume 14 into the second optical waveguide 21. Additionally, the protective layer 17 is preferably chemically inert to the fluid in the sample volume 14. For example, on a silicon substrate 18, the protective layer 17 can be produced by oxidizing the first part 70 of the surface to silicon dioxide.

[0094] In a first usage example of the in Fig. In the embodiment of the biotechnological analysis module 1 shown in Figure 3, the first microfluidic channel 37 can be connected to the reactor 2. This connection of the first microfluidic channel 37 to the reactor 2 (not shown) can, for example, be made by the interface unit 33 in the case of a spaced-apart reactor 2 (see Figure 3). Fig. 7) take place, in particular through the interface unit (fluidic connection) 33c. It is also conceivable that a fluid is extracted from reactor 2 by means of a pipetting robot and supplied to the first microfluidic channel 37.

[0095] The first microfluidic channel 37 can be referred to as the inlet channel in this case. Certain substances / molecules may be dissolved in the fluid taken from reactor 2 and fed into the first microfluidic channel 37, which can diffuse through membrane 39 into the second microfluidic channel 38. The second microfluidic channel 38 can be referred to as the filtrate channel in this case.

[0096] The second microfluidic channel 38 can have a connection to the sample volume 14 as well as to the storage volume 27. The nutrient or reagent solution 28 can advantageously be a pure buffer solution. It is also conceivable that it is a pure solvent, in particular water. The use of a buffer solution or a pure solvent is particularly advantageous because the filtrate channel, i.e., the second microfluidic channel 38, is then free of unwanted substances / molecules. The use of a buffer solution is particularly advantageous if, for example, certain ion concentrations in the feed and filtrate channels should not differ. If the ion concentration in the feed and filtrate channels is identical for the specific ions, no osmotic pressure arises for these ions.

[0097] By separating the first microfluidic channel 37 from the second microfluidic channel 38 using membrane 39, a targeted enrichment of specific substances / molecules in the second microfluidic channel 38 can be achieved, since unwanted substances / molecules cannot pass from the first microfluidic channel 37 into the second microfluidic channel 38. For example, membrane 39 is designed to allow only substances or molecules up to a certain size to pass through.

[0098] By enriching the desired substances / molecules and / or removing the undesired substances / molecules in the second microfluidic channel 38, which is connected to the sample volume 14 via at least one microfluidic channel 13, the signal-to-noise ratio can be increased during sample analysis. In particular, during spectroscopic analysis, light from the first optical waveguide 20 can be coupled into the sample volume 14 for excitation. The resulting fluorescence light in the sample volume 14 is coupled into the second optical waveguide 21 and can be output via the output port 23. The light output at the output port 23 can, for example, be measured with a spectrometer 57 (see Fig. 5 and Fig. 7) be analyzed to detect specific molecules.

[0099] By removing unwanted substances / molecules and thereby enriching the desired substances / molecules in the sample volume 14, the signal-to-noise ratio in the spectroscopic analysis is advantageously increased.

[0100] In a second usage example of the in Fig. In the embodiment of the biotechnological analysis module 1 shown in Figure 3, the first microfluidic channel 37 is connected, for example, to the storage volume 27. The storage volume 27 contains a nutrient or reagent solution 28. The second microfluidic channel 38 is connected, for example, to the reactor 2.

[0101] Membrane 39 can be configured, in particular, to allow nutrients, which are supplied to membrane 39 from storage volume 27 via the first microfluidic channel 37, to pass into the second microfluidic channel 38. Furthermore, membrane 39 can be configured to allow reaction products from reactor 2, which are supplied to membrane 39 from reactor 2 via the second microfluidic channel 38, to pass into the first microfluidic channel 37.

[0102] This allows for cross-flow filtration. Undesired reaction products are removed from reactor volume 3, and reactants can be added.

[0103] The selectivity of the membrane 39 can be determined, for example, by a pressure difference between the first microfluidic channel 37 and the second microfluidic channel 38, by osmotic pressure and / or the particle size.

[0104] For example, reactor 2 could be a bioreactor. The fluid supplied via the second microfluidic channel 38 of membrane 39 and the sample volume 14 can, for example, be purified of unwanted metabolic end products by allowing these products to pass through membrane 39 into the first microfluidic channel 37. Larger components in the fluid, such as macronutrients and / or cells, are prevented by membrane 39 from entering the first microfluidic channel 37.

[0105] The nutrient or reagent solution 28 from the storage volume 27 can be guided via the first microfluidic channel 37 to the membrane 39 and through it into the second microfluidic channel 38. This allows the reactor 2 to be continuously supplied with nutrients / reagents. Advantageously, this ensures a constant concentration of nutrients / reagents in the reactor 2.

[0106] The photonic circuit 12 of the biotechnological analysis module 1 can be used in this application example to monitor the filtration process. For example, as described in the previous application example, the concentration of certain substances / molecules can be determined using spectroscopy. It is also conceivable that the first optical waveguide 20 and the second optical waveguide 21 are arranged on the sample volume 14 in such a way that the measurement of an optical density is enabled. The optical density can be used, in particular, to determine the biomass in the reactor 2.

[0107] The Fig. Figure 4 shows an embodiment of the valve unit 40. The microfluidic system 11 comprises the valve unit 40. The valve unit 40 is arranged on the at least one microfluidic channel 13. The valve unit 40 is configured to adjust the flow through the at least one microfluidic channel 13.

[0108] In the example shown, the valve unit 40 comprises a first valve 41, a second valve 42, and a third valve 43. Furthermore, the valve unit 40 includes a control input 44. In the example shown, the control input 44 is configured as an optical control connection. The control connection is connected to the optical fiber assembly 19.

[0109] The first valve 41 comprises a first control input 45, wherein the first control input 45 is connected to a first control optical waveguide 46. The cross-section of the section 47 of the at least one microfluidic channel 13, which forms the first valve 41, is variable depending on the light power applied to the first control input 45.

[0110] The second valve 42 and the third valve 43 also each include a control input, wherein the control input is connected to a respective control optical waveguide in order to change the cross-section of the at least one microfluidic channel 13 at the respective section depending on the applied light power.

[0111] The first valve 41 comprises an expansion volume 48, which is connected to the first control optical waveguide 46 via the first control input 45. At the interface with the section 47 of the at least one microfluidic channel 13, the expansion volume 48 is bounded by a diaphragm 49.

[0112] The expansion volume 48 is filled, for example, with a fluid that preferably has a high coefficient of thermal expansion. When light power is applied to the first control input 45 via the first control optical waveguide 46, the fluid in the expansion volume 48 heats up and expands. This causes the membrane 49 to bulge and reduces the cross-section of section 47 of the at least one microfluidic channel 13. In particular, the expansion of the expansion volume 48 can be controlled depending on the light power applied to the first control input 45. The flow through the at least one microfluidic channel 13 can also be completely stopped.

[0113] It is also conceivable that, due to the heating of the fluid, a portion of it transitions into a gaseous state, resulting in a disproportionate expansion. The term "disproportionate" here refers to the volume change expected from expansion alone, according to the coefficient of thermal expansion, without a change in the state of matter.

[0114] A particular advantage is that the expansion of the expansion volume 48, and thus the position of the first valve 41, is reversible. If no more light power is supplied to the expansion volume 48 via the first control input 45, it cools down and the valve opens. The heat is preferably dissipated via the substrate 18 of the photonic circuit 12.

[0115] However, it is also conceivable that applying light power to the first control input 45 causes a non-reversible phase transition in the expansion volume 48. For example, the first valve 41 can be closed once by the applied light power triggering a non-reversible chemical reaction that produces a gas in the expansion volume 48. The gas formation significantly increases the volume, and the first valve 41 closes.

[0116] In the example shown, the first valve 41 is closed, the second valve 42 is open, and the third valve 43 is closed.

[0117] The optical control of the valves 41, 42, 43 is effected via the control input 44, the optical fiber assembly 19, and an optical multiplexer unit 50. The optical fiber assembly 19 is connected to the control input 44. Light can be coupled into the optical fiber assembly 19 at the control input 44. The optical multiplexer unit 50 is configured to distribute the light coupled into the control input 44 to the various control optical fibers 46 of the valves 41, 42, 43. In the example shown, the optical multiplexer unit 50 comprises three switching modules 51a, 51b, 51c.

[0118] The first switching module 51a is connected to the control input 44 via the optical fiber arrangement 19. In a first operating state, the first switching module 51a is configured to forward the light coupled to the control input 44 to the second switching module 51b. In a second operating state, the first switching module 51a is configured to continue forwarding the light coupled to the control input 44 to the second switching module 51b, whereby a portion of the light power received by the control input 44 is directed to the first control optical fiber 46.

[0119] For example, the first and second operating states of the switching module 51a can be selected by an electrical signal.

[0120] In the Fig. In position 4, the first switching module 51a is in its second operating state. A portion of the light power received by the control input 44 is directed to the first control optical fiber 46. This closes the first valve 41. The remaining light power is directed to the second switching module 51b.

[0121] The second switching module 51b receives light power from the first switching module 51a and, in a first operating state, forwards it to the third switching module 51c. In a second operating state, the second switching module 51b is configured to forward a portion of the received light power to the control optical fiber, which is connected to the control input of the second valve 42. Simultaneously, in the second operating state, the second switching module 51b is configured to forward the remaining portion of the light power to the third switching module 51c. In the Fig. In the configuration shown in Figure 4, the second switching module 51b is in its first operating state.

[0122] The third switching module 51c, and in this case the last switching module 51c, is configured to receive light power from the second switching module 51b. In a first operating state, the third switching module 51c is configured not to direct the received light power to the control optical waveguide, which is connected to the control input of the third valve 43. In a second operating state, the third switching module 51c is configured to direct a portion of the received light power to the control optical waveguide, which is connected to the control input of the third valve 43. In the Fig. In the configuration shown in Figure 4, the third switching module 51c is in its second operating state.

[0123] By periodically changing the operating states of the switching modules 51a, 51b, 51c, a directed pumping action can be generated along the at least one microfluidic channel 13 by alternately opening and closing the valves 41, 42, 43. The fluid can be transported in both directions.

[0124] The Fig. Figure 5 shows the spectroscopy on the biotechnological analysis module 1 with an optical coupler unit 52. In the illustrated embodiment, the optical coupler unit 52 is not part of the assembly 10, but is arranged at a distance from it. It is also conceivable that the optical coupler unit 52 is part of the photonic circuit 12.

[0125] The optical coupler unit 52 comprises an optical input port 53, an optical output port 54, and an optical bidirectional port 55. The optical input port 53 is connected to a light source 56, so that light emitted by the light source 56 can be supplied to the optical coupler unit 52. Preferably, the light source 56 is configured as a laser. The connection between the light source 56 and the optical coupler unit 52 can be made, for example, by means of optical fibers.

[0126] The optical output port 54 is connected, for example, to the spectrometer 57.

[0127] The optical, bidirectional connection 55 is connected to the first optical waveguide 20 of the optical waveguide arrangement 19 via the input connection 22 of the photonic circuit 12. The light from the light source 56 coupled into the optical input connection 53 can thus be coupled into the sample volume 14.

[0128] Light from the sample volume 14 can be coupled into the first optical waveguide 20 and supplied via the optical waveguide arrangement 19 and the input connection 22 to the bidirectional connection 55 of the optical coupler unit 52.

[0129] The optical coupler unit 52 is configured to output the light received at the optical, bidirectional port 55 at the optical output port 54. Thus, the light coupled from the sample volume 14 into the first optical waveguide 20 can be analyzed using the spectrometer 57.

[0130] The described arrangement is particularly advantageous for carrying out reflection measurements.

[0131] The second optical waveguide 21 of the optical waveguide arrangement 19 is in Fig. The second optical waveguide 21 is arranged outside the line-of-sight 58 of the first optical waveguide 20. This means that light coupled out of the first optical waveguide 20 cannot be directly coupled into the second optical waveguide 21. The arrangement of the second optical waveguide 21 outside the line-of-sight 58 is particularly advantageous when scattered and / or fluorescence light from the sample volume 14 is coupled into the second optical waveguide 21, since in this case the light coupled into the sample volume 14 from the first optical waveguide 20 does not reduce the signal-to-noise ratio.

[0132] The photonic circuit 12 comprises a photodetector 59. The photodetector 59 is connected to the second optical waveguide 21, such that light coupled from the sample volume 14 into the second optical waveguide 21 is directed to the photodetector 59. The photodetector 59 is configured to convert the received light into an electrical output signal 60. The electrical output signal 60 contains information about the luminous power of the light received by the photodetector 59. Preferably, the photodetector 59 is configured as a photodiode. The photodiode can, for example, be produced in the semiconductor substrate 18 by local doping. The electrical output signal 60 can be a photodiode current or an electrical voltage after the photodiode current has been converted into a voltage by means of a transimpedance amplifier (TIA).

[0133] The photonic circuit 12 further comprises an analog-to-digital converter (ADC) 61. In the illustrated embodiment, the ADC 61 receives the electrical output signal 60, preferably in the form of a voltage. The ADC 61 is configured to convert the received measurement signal (in this case, the electrical output signal 60) into a digital signal 62 and output it as a digital signal 62. The digital signal 62 can be, for example, transmitted via the interface unit 33 (see Figure 3). Fig. 7), in particular via the interface unit (electrical connection) 33b. It is conceivable that the digital signal 62 could be output to an external storage module 69 (see Fig. 7) is sent to be recorded there. The external storage module 69 can be part of the central control and / or evaluation device 65 (see Fig. 7) be.

[0134] The Fig. Figure 6 shows a spectroscopy system with an integrated light source 56. The photonic circuit 12 comprises a light source 56, preferably in the form of a laser. The laser can, for example, be produced in the semiconductor substrate 18 by local doping. The light emitted by the light source 56 is coupled into the sample volume 14 via the optical waveguide arrangement 19, in particular the first optical waveguide 20. The second optical waveguide 21 of the optical waveguide arrangement 19 is arranged in the line-of-sight connection 58 of the first optical waveguide 20. The light coupled into the sample volume 14 from the first optical waveguide 20 propagates along the line-of-sight connection 58 and is scattered and absorbed in the process. The light coupled into the second optical waveguide 21 therefore typically has a lower intensity than the light coupled into the sample volume 14.The ratio of the two intensities in the first optical waveguide 20 and the second optical waveguide 21 is a measure of the optical density in the sample volume 14 and provides information about the biomass in the sample volume 14, for example.

[0135] The intensity of the light coupled into the second optical waveguide 21 can be determined, for example, via the photodetector 59. The photonic circuit 12 also includes the photodetector 59. The photodetector 59 receives the light coupled into the second optical waveguide 21 and converts it into the electrical output signal 60. The photonic circuit 12 also includes the ADC 61, which receives the electrical output signal 60 and converts it into a digital signal 62. The digital signal 62 can be accessed via the interface unit 33 (see Fig. 7), in particular via the interface unit (electrical connection) 33b, to the central control and / or evaluation device 65 (see Fig. 7) be transmitted. The central control and / or evaluation device 65 can in particular be configured to determine the optical density in the sample volume 14 using the digital signal 62.

[0136] The Fig. Figure 7 shows an embodiment of a biotechnological analysis system 100 according to the invention. The biotechnological analysis system 100 comprises a first biotechnological analysis module 1 and at least one second biotechnological analysis module 63. The biotechnological analysis system 100 further comprises a common carrier module 64 and the central control and / or evaluation device 65. The central control and / or evaluation device 65 is configured to receive first measurement signals for the sample to be analyzed from the first biotechnological analysis module 1. Furthermore, the central control and / or evaluation device 65 is configured to receive second measurement signals for the sample to be analyzed from the at least one second biotechnological analysis module 63.

[0137] The first biotechnological analysis module 1 and the common carrier module 64 are detachably plugged together. The optical fiber assembly 19 of the first biotechnological analysis module 1 is connected to an optical fiber assembly 66 on the carrier module 64 via the interface unit 33. The optical fiber assembly 19 of at least one second biotechnological analysis module 63 is also connected to the optical fiber assembly 66 on the carrier module 64. The interface unit (optical connection) 33a can be implemented, in particular, as a PC / FC or PC / APC connection, as is known from the telecommunications industry.

[0138] The optical waveguide arrangement 66 on the carrier module 64 is configured to transmit light from the light source 56 sequentially or in parallel to the optical waveguide arrangements 19 of the first and at least one second biotechnological analysis module 1, 63. For this purpose, the carrier module 64 can include an optical multiplexer unit 50 (see Fig. 4, not in Fig. 7 shown).

[0139] For example, the light from the light source 56 is transmitted to the optical waveguide arrangement 66 on the carrier module 64 by means of the optical coupler unit 52.

[0140] The light signals transmitted from one and / or at least one second biotechnological analysis module 1, 63 via its optical waveguide arrangement 19 and the interface unit 33, in particular the interface unit (optical connection) 33a, to the optical waveguide arrangement 66 on the carrier module 64 are transmitted to the optical, bidirectional connection 55 of the optical coupler unit 52. The transmitted light signals are output by the optical coupler unit 52 at the optical output connection 54.

[0141] The optical output port 54 is connected to the spectrometer 57. The spectrometer 57 is configured to generate measurement signals from the received light signals and transmit these to the central control and / or evaluation unit 65. The central control and / or evaluation unit 65 is configured to receive the measurement signals, assign them to the individual biotechnological analysis modules 1, 63, and store them in the storage module 69.

[0142] The carrier module 64 includes a corresponding interface unit for the interface unit 33 of the biotechnological analysis module 1, 63. The interface unit 33 and the corresponding interface unit are designed to exchange optical signals, electrical signals and / or fluids between the carrier module 64 and the biotechnological analysis modules 1, 63.

[0143] The central control and / or evaluation device 65 is configured to receive measurement signals from the individual biotechnological analysis modules 1, 63 via the carrier module 64. For example, the central control and / or evaluation device can be configured to receive, process, and store the digital signal 62 from an ADC 61. The received and, if applicable, processed measurement signal can be used by the central control and / or evaluation device 65 to determine settings for controlling the individual biotechnological analysis modules 1, 63. These settings can be transmitted to the biotechnological analysis modules 1, 63 via electrical or optical signals and / or fluid flows through the carrier module 64.

[0144] The carrier module 64 comprises an electrical network 67 (solid line) and a fluid system 68 (dotted line). Electrical signals can be exchanged between the central control and / or evaluation unit 65 and the individual biotechnological analysis modules 1, 63 via the electrical network 67. For this purpose, the electrical network 67 is connected to the corresponding interface units. Fluids can be exchanged between the individual biotechnological analysis modules 1, 63 and / or the central control and / or evaluation unit 65 via the fluid system 68. For this purpose, the fluid system 68 is connected to the corresponding interface unit. In this case, a fluid reservoir can be arranged in the central control and / or evaluation unit 65, from which the individual biotechnological analysis modules 1, 63 are supplied with fluid.

[0145] For example, the nutrient content can be determined by the central control and / or evaluation device 65 from the received electrical and optical measurement signals. The central control and / or evaluation device 65 transmits parameters to the corresponding biotechnological analysis module 1, 63, which control the supply of nutrients from the storage volume 27 into the reactor 2. In particular, light signals or electrical signals can be used for this purpose, which control the valves 41, 42, 43 of the valve unit 40.

[0146] It is particularly conceivable that a control loop is formed by the central control and / or evaluation device 65, with which process parameters of the reactor 2 are set to a specific target value.

[0147] The central control and / or evaluation device 65 can include the storage module 69, on which the received and / or processed measurement signals and / or the determined settings are stored.

[0148] The invention is not limited to the described embodiments. Within the scope of the invention, all described and / or drawn features can be combined with one another as desired. Reference symbol list 1 Biotechnological Analysis Module 2 reactors 3 Reactor volume 4 Reactor floor 5 Reactor wall 6 Mixing device 7 Stirring rod 8 Reactor ceiling 9 Membran 10. Combination of the microfluidic system and the photonic circuit 11 Microfluidic system 12 Photonic circuit 13 Microfluidic channel 14 Sample volume 15 First connection of the reactor to the sample volume 16 Second connection 17 Protective layer 18 Substrat 19 Optical fiber arrangement 20 First optical fiber 21 Second optical fiber 22 Input connection 23 Output port 24 Electrical measuring unit 25 Electrical wiring 26 Electrical output connection 27 storage volume 28 Nutrient or reagent solution 29 Valve unit 30 Tax receipt 31 Electrical control line 32 Electrical control connection 33 Interface unit 33a Interface unit (optical connection) 33b Interface unit (electrical connection) 33c Interface Unit (fluidic connection) 34 Temperature control element 35 Electrical temperature control input 36 Electrical supply line 37 First microfluidic channel 38 Second microfluidic channel 39 Membran 40 valve unit 41 First valve 42 Second valve 43 Third valve 44 Control input 45 First tax receipt 46 First control optical fiber 47 Section of at least one microfluidic channel 48 Expansion volume 49 Membran 50 Optical Multiplexer Unit 51a First switching module 51b Second switching module 51c Third switching module 52 Optical coupler unit 53 Optical input connector 54 Optical output connector 55 Optical, bidirectional connection 56 Light source 57 spectrometers 58 line-of-sight connection 59 Photodetector 60 Electrical output signal 61 Analog-to-Digital Converters (ADCs) 62 Digital Signal 63 At least a second biotechnological analysis module 64 Carrier module 65 Central control and / or evaluation device 66 Optical fiber arrangement on the carrier module 67 Electrical network 68 Fluid system 69 memory module 70 First part of the surface of the photonic circuit 71 Second part of the surface of the photonic circuit 100 Biotechnological Analysis System

Claims

[1] Biotechnological analysis module (1) for analyzing a sample, wherein the biotechnological analysis module (1) comprises a reactor (2) and a composite (10) of a microfluidic system (11) and a photonic circuit (12) having the following features: - the photonic circuit (12) has a surface that is directed towards the sample to be analyzed, wherein a first part (70) of the surface can be brought into contact with the sample to be analyzed and wherein a second part (71) of the surface is connected to the microfluidic system (11); - the first part (70) of the surface of the photonic circuit (12) together with the microfluidic system (11) encloses a sample volume (14) which is connected to the reactor (2), making it possible to introduce the sample to be analyzed from the reactor (2) into the sample volume (14); - the microfluidic system (11) comprises at least one microfluidic channel (13) which is connected to the sample volume (14) and / or the reactor (2) for the supply and / or removal of a fluid; - the photonic circuit (12) comprises an optical waveguide arrangement (19) with one optical waveguide (20, 21) or several optical waveguides (20, 21); - the optical waveguide arrangement (19) is: a) arranged on the enclosed sample volume (14) such that light from the optical waveguide arrangement (19) can be coupled into the enclosed sample volume (14) and / or that light from the enclosed sample volume (14) can be coupled into the optical waveguide arrangement (19); and / or b) arranged on the at least one microfluidic channel (13) in such a way that light which can be transmitted via the optical waveguide arrangement (19) can be used to control the flow rate of the amount of fluid flowing in the at least one microfluidic channel (13). [2] Biotechnological analysis module (1) according to claim 1, characterized by the following characteristic: - the reactor (2) is designed to control and / or monitor biochemical reactions and / or bioprocesses. [3] Biotechnological analysis module (1) according to claim 1 or 2, characterized by the following characteristics: - the reactor (2) is part of the system (10) consisting of the microfluidic system (11) and the photonic circuit (12); or - the reactor (2) is arranged at a distance from the assembly (10) of the microfluidic system (11) and the photonic circuit (12), wherein the reactor (2) is connected to the at least one microfluidic channel (13) for the exchange of fluid between reactor (2) and sample volume (14). [4] Biotechnological analysis module (1) according to claim 3, characterized by the following characteristics: - a lower region of the reactor (2), wherein the reactor (2) is part of the assembly (10), comprises the sample volume (14), wherein a bottom of the reactor (2) is formed by at least the first part (70) of the surface of the photonic circuit (12); or - the reactor (2), which is part of the complex (10), is: a) arranged on a surface of the microfluidic system (11); or b) enclosed within the microfluidic system (11); and wherein the at least one microfluidic channel (13) connects the reactor (2) to the sample volume (14) for fluid exchange. [5] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the photonic circuit (12) comprises one or more of the following materials: a) Silicon and / or silicon dioxide; b) GaAs and / or GaAsP and / or InGaAsP; c) Lithium niobate; - the microfluidic system (11) comprises one or more of the following materials: a) Plastic; b) Ceramics; c) Glass ceramics; d) Glass. [6] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristic: - the second part (71) of the surface of the photonic circuit (12) is metallurgically connected to the microfluidic system (11). [7] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the second part (71) of the surface of the photonic circuit (12) is bonded to the microfluidic system (11); or - the microfluidic system (11) is a 3D printed part and is applied to the second part (71) of the surface of the photonic circuit (12) by an additive manufacturing process; or - the microfluidic system (11) is an injection-molded part and is applied to the second part (71) of the surface of the photonic circuit (12) by injection molding. [8] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristic: - a protective layer (17) is provided and applied to the first part (70) of the surface of the photonic circuit (12) to separate the photonic circuit (12) from the sample volume (14). [9] Biotechnological analysis module (1) according to claim 8, characterized by the following characteristics: - the protective layer (17) is transparent to the wavelength of the light which can be coupled into and / or out of the sample volume (14) from the optical waveguide arrangement (19); and / or - the protective layer (17) is chemically inert to the fluid and the sample. [10] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the microfluidic system (11) comprises at least one first and one second microfluidic channel (37, 38), wherein the first and the second microfluidic channel (37, 38) are separated from each other by a membrane (39); and - the membrane (39) is designed to prevent certain particles and / or molecules from passing from the first microfluidic channel (37) into the second microfluidic channel (38). [11] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the microfluidic system (11) comprises at least one storage volume (27), in which a fluid in the form of a nutrient solution or a reagent solution (28) can be introduced; - at least one storage volume (27) is connected to the reactor (2) and / or the sample volume (14) via at least one microfluidic channel (13). [12] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristic: - the microfluidic system (11) comprises a valve unit (40) with at least one first valve (41), wherein the at least one first valve (41) is arranged in the at least one microfluidic channel (13) and is configured to control the flow through the at least one microfluidic channel (13). [13] Biotechnological analysis module (1) according to claim 12, characterized by the following characteristic: - the valve unit (40) comprises a pneumatic control inlet, wherein the pneumatic control inlet is designed to be subjected to an overpressure or underpressure and wherein the flow through the at least one microfluidic channel (13) is adjustable depending on the applied pressure. [14] Biotechnological analysis module (1) according to claim 12, characterized by the following characteristic: - the valve unit (40) comprises a control input (44), wherein the control input (44) is connected to at least one first control optical waveguide (46) of the optical waveguide arrangement (19) of the photonic circuit (12) or to an electrical control line of the photonic circuit (12), and wherein the flow through the at least one microfluidic channel (13) is adjustable depending on the control signal applied to the control input (44). [15] Biotechnological analysis module (1) according to claim 14, characterized by the following characteristic: - the at least one first valve (41) is formed by a section (47) of the at least one microfluidic channel (13), the cross-section of which can be changed depending on the applied light power from the at least one first control optical waveguide (46) or the applied electrical power at the control input (44). [16] Biotechnological analysis module (1) according to any one of claims 12 to 15, characterized by the following characteristic: - the valve unit (40) comprises at least a second valve (42) which is arranged in the at least one microfluidic channel (13) next to the at least one first valve (41), wherein a directed transport of the fluid in the at least one microfluidic channel (13) can be generated by alternating switching of the first and second valve (41, 42). [17] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - an optical coupler unit (52) is provided with an optical input port (53), an optical output port (54) and an optical, bidirectional port (55); - the optical waveguide arrangement (19) includes a first optical waveguide (20); - the first optical waveguide (20) is connected at its first end to the optical, bidirectional connection (55); - the first optical waveguide (20) is connected at its second end to the sample volume (14); - the optical coupler unit (52) is designed to output light which can be supplied to the optical coupler unit (52) at the optical input port (53) at the optical, bidirectional port (55), and to output light emitted from the sample volume (14) which can be supplied to the optical coupler unit (52) at the optical, bidirectional port (55) at the optical output port (54). [18] Biotechnological analysis module (1) according to claim 17, characterized by the following characteristic: - the optical coupler unit (52) is designed to output the light supplied at the optical, bidirectional connection (55) at the optical output connection (54) depending on its wavelength. [19] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the optical waveguide arrangement (19) comprises a first optical waveguide (20) and a second optical waveguide (21); - the first optical waveguide (20) is designed to couple light into the sample volume (14); - the second optical waveguide (21) is designed to receive light from the sample volume (14); - the first and the second optical waveguide (20, 21) are arranged relative to each other such that: a) a line-of-sight connection (58) exists between the first and the second optical waveguides (20, 21) through the sample volume (14); or b) the second optical waveguide (21) is arranged outside a line-of-sight connection (58) through the sample volume (14) to the first optical waveguide (20). [20] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - a temperature control element (34) is provided; - the temperature control element (34) is designed to adjust the temperature of the sample in the sample volume (14) and / or of the fluid in the reactor (2). [21] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the photonic circuit (12) comprises at least one light source (56), wherein the light source (56) is configured to generate the light and couple it into the optical waveguide arrangement (19); and / or - the photonic circuit (12) comprises at least one photodetector (59), wherein the photodetector (59) is connected to the optical waveguide arrangement (19) and is configured to convert the light coupled into the optical waveguide arrangement (19) into an electrical signal. [22] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the photonic circuit (12) comprises an electrical measuring unit in the form of an electrical sensor and / or an electrochemical sensor and / or an electrode; - the electrical measuring unit is arranged on the first part (70) of the surface of the photonic circuit (12) so that the electrical measuring unit can be brought into physical contact with the sample in the sample volume (14). [23] Biotechnological analysis module (1) according to claim 21 or 22, characterized by the following characteristics: - the photonic circuit (12) includes an analog-to-digital converter (ADC) (61); - the ADC (61) is designed to convert a measurement signal from the electrical measuring unit and / or the electrical signal from the photodetector (59) into a digital signal (62). [24] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - the optical waveguide arrangement (19) comprises an optical multiplexer unit (50) and / or an optical demultiplexer unit; - the optical multiplexer unit (50) is configured to split the light from one optical waveguide into several outgoing optical waveguides and to adjust the intensity of the light in the several outgoing optical waveguides; and / or the optical demultiplexer unit is configured to: a) to combine the light from several incoming optical waveguides into a single outgoing optical waveguide; and / or b) to transmit the light from at least one optical waveguide from several incoming optical waveguides, but not from all of the several optical waveguides, to the individual outgoing optical waveguide. [25] Biotechnological analysis module (1) according to any one of the preceding claims, characterized by the following characteristics: - an interface unit (33) is provided; - the interface unit (33) is designed to transmit light: a) to receive from outside the biotechnological analysis module (1) and couple into the optical waveguide arrangement (19); and / or b) to receive from the optical fiber arrangement (19) and transmit it outside the biotechnological analysis module (1); and / or - the interface unit (33) is designed to: a) to take up from outside the biotechnological analysis module (1) and direct it into the at least one microfluidic channel (13); and / or b) to receive via at least one microfluidic channel (13) and direct it outside the biotechnological analysis module (1); and / or - the interface unit (33) is designed to transmit electrical signals: a) to receive from outside the biotechnological analysis module (1) and to transmit it to the photonic circuit (12); and / or b) to be received by the photonic circuit (12) and transmitted outside the biotechnological analysis module (1). [26] Biotechnological analysis system (100) comprising a first and at least one second biotechnological analysis module (1, 63), wherein the first and the at least one second biotechnological analysis module (1, 63) are constructed according to one of the preceding claims, characterized by the following characteristics: - a common carrier module (64) is provided, wherein the first and at least one second biotechnological analysis module (1, 63) are arranged on the common carrier module (64); - a central control and / or evaluation device (65) is provided; - the central control and / or evaluation device (65) is designed to receive first measurement signals for the sample to be analyzed from the first biotechnological analysis module (1) and to receive second measurement signals for the sample to be analyzed from the at least second biotechnological analysis module (63). [27] Biotechnological analysis system (100) according to claim 26, characterized by the following characteristic: - the at least one microfluidic channel (13) of the first biotechnological analysis module (1) is connected to the at least one microfluidic channel (13) of the at least one second biotechnological analysis module (63), so that an exchange of fluids between the reactor (2) of the first biotechnological analysis module (1) and the reactor (2) of the at least one second biotechnological analysis module (63) is possible. [28] Biotechnological analysis system (100) according to claim 26 or 27, characterized by the following characteristics: - the first biotechnological analysis module (1) is attached to the carrier module (64) via a detachable plug and / or snap connection and / or a magnetic connection; - at least one second biotechnological analysis module (63) is attached to the carrier module (64) via a detachable plug and / or snap connection and / or magnetic connection. [29] Biotechnological analysis system (100) according to claim 28, characterized by the following characteristic: - at least one second biotechnological analysis module (63) can be removed from the carrier module (64) without interrupting the operation of the first biotechnological analysis module (1). [30] Biotechnological analysis system (100) according to one of claims 26 to 29, characterized by the following characteristics: - a light source (56) is provided; - the light source (56) is: a) connected to an optical waveguide arrangement (66) in the carrier module (64), wherein the optical waveguide arrangement (66) of the carrier module (64) is configured to transmit light from the light source (56) sequentially or in parallel to the optical waveguide arrangements (19) of the first and of at least one second biotechnological analysis module (63); or b) connected to the optical waveguide arrangement (19) of the first biotechnological analysis module (1), wherein the optical waveguide arrangement (19) is configured to transmit the light received from the light source (56) to the optical waveguide arrangement (19) of the respective adjacent, at least one second biotechnological analysis module (63). [31] Biotechnological analysis system (100) according to one of claims 26 to 30, characterized by the following characteristics: - a spectrometer (57) is provided; - the spectrometer (57) is connected to an optical waveguide arrangement (66) in the carrier module (64), wherein the optical waveguide arrangement (66) of the carrier module (64) is configured to receive light from the optical waveguide arrangements (19) of the first biotechnological analysis module (1) and of at least one second biotechnological analysis module (63) and to transmit it sequentially to the spectrometer (57). [32] Biotechnological analysis system (100) according to one of claims 26 to 31, wherein the first biotechnological analysis module (1) and the at least one second biotechnological analysis module (63) comprise an interface unit (33) according to claim 25, wherein the carrier module (64) has an interface unit corresponding to the respective interface unit (33).

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