Apparatus and method for sensing, measuring, recording and controlling light exposure to a sample - Patent Application 20070122997

Abstract

The present invention relates to an apparatus 15 and related methods, comprising the apparatus 15 including at least one interior space 16 and designed to contain at least one chemical and / or biological sample, or comprising at least one container 20 designed to contain at least one chemical and / or biological sample 28, and at least one illumination means 24 for illuminating the chemical and / or biological sample 28 in the interior space 16, the apparatus 15 further comprising or being provided with at least one light measurement unit 26 designed to measure the intensity of light transmitted through and / or scattered from the chemical and / or biological sample 28 in the interior space 16. The light measurement unit 26 is a type of detection device that detects light exposure of the chemical and / or biological sample 28 during the illumination process (e.g., optogenetic control, photoactivation, or photocatalysis), preferably in real time, to effectively control the illumination of the sample 28.

Description

[Technical Field]

[0001] The present invention relates to an apparatus comprising at least one internal space designed to contain at least one chemical and / or biological sample or to contain at least one container designed to contain at least one chemical and / or biological sample, and at least one illumination means for irradiating the chemical and / or biological sample in the internal space. The present invention also relates to a method for controlling light exposure to at least one chemical and / or biological sample, in which the sample is placed in the internal space of the illumination apparatus and illuminated by at least one illumination means emitting light comprising at least one biologically and / or chemically active wavelength. The present invention also relates to a method for calibrating an optogenetic illumination apparatus comprising at least one illumination means. [Background technology]

[0002] Optogenetics is a technology that combines light with genetically encoded light-sensitive proteins to control the behavior or biochemical processes of living cells and organisms. Optogenetic technology is increasingly being applied in many laboratories worldwide, and several technological developments have made it a booming field. For example, the exploration and combination of functional domains to create novel light-sensitive photoswitches that can control specific cellular behaviors has led to the creation of diverse tools with diverse functions [1,2]. However, despite advances in phototransduction technology, particularly at the microscopic level, enabling unprecedented control of in vitro and in vivo processes through illumination, standardized and useful laboratory or biomanufacturing equipment to leverage this promising technology for a broader range of cell culture-based applications has yet to be available on the market. To date, home-built devices have dominated the laboratory landscape, but there is a growing need for technically mature and user-optimized laboratory equipment to reproducibly and reliably harness this promising technology.

[0003] Olsen et al. (2014) describe a method for controlling gene expression dynamics with light by using an apparatus equipped with independently programmable blue, green, red, and far-red light-emitting diodes (LEDs) to illuminate 64 standard test tubes with each wavelength at a regulated intensity. This device allows for the transmission of optical signals to exponentially growing bacterial cultures in a shaker incubator. To this end, an array of individually controllable LEDs is placed below the test tubes and used to provide programmed dynamic light input to the bacterial cultures in the test tubes. Each culture tube is optically isolated by opaque polystyrene foam [3].

[0004] Gerhardt et al. (2016) describe a device that transmits two independent optical signals to each well of a 24-well culture plate. The device includes a printed circuit board (PCB) with a secure digital (SD) card reader, a microcontroller, three LED drivers, 48 solderless LED sockets, a power conditioning circuit, and other standard electronic components. A chassis houses the assembled PCB and 24-well plate. The LEDs are placed on the PCB, which is attached to a mounting plate positioned below the 24-well plate. The black-walled 24-well plate has a clear plastic bottom and is aligned and secured by a plate adapter. An adhesive film plate cover provides a sealed environment for each well. Laser-cut nitrile gaskets are placed at each interface above the PCB to reduce optical contamination. A lid is placed on top of the plate, and the whole assembly is secured with wing nuts. [4]

[0005] US Patent No. 2018 / 0016538 A1 discloses an apparatus, system, and method for an illumination optoplate configured to specifically illuminate wells in a cell culture plate. The apparatus includes a base and plate adapter configured for use with 96-well plates or other common culture plates, such as 6-, 12-, 24-, 48-, or 384-well plates. The culture plate is placed on top of the adapter, with various openings corresponding to the LED lighting fixtures in the adapter positioned directly beneath the corresponding wells in the tissue culture plate. The optoplate's low-profile design allows it to be used inside an incubator or under a microscope.

[0006] Zhao et al. (2018) describe the use of light panels placed around a small bioreactor to illuminate optogenetically engineered yeast cells and control cellular metabolism to specifically increase the yield of two alcohols.[5]

[0007] Steel et al. (2019) have developed an automated experimental platform (Chi-Bio) for biological research. In addition to continuous culture functions (turbidity control, heating, and stirring), the platform incorporates adjustable light output at various wavelengths and spectroscopy. It incorporates a UV LED for sterilization and a 650 nm laser for optical density measurement, as well as a seven-wavelength LED for optogenetic actuation or fluorescence excitation. Fluorescence emission can be measured using a chip-based spectrometer. This device can be used to employ fluorescence measurement for in silico feedback control of optogenetic light input to resolve nonlinearities in optogenetic fluorescent protein expression [6].

[0008] Wong et al. (2018) describe an extensible DIY framework (eVOLVER) that can be configured to perform high-throughput growth experiments in molecular evolution, systems biology, and microbiology. The system is equipped with an LED / photodiode sensor pair for optical density measurements at 900 nm, which can be converted to cell density. Furthermore, the device can be reconfigured to include an LED for optogenetics studies [7].

[0009] However, prior art devices are not designed or equipped to measure or monitor the actual light exposure of cell cultures. Therefore, recording of the actual light exposure of chemical and / or biological samples is not achieved. Furthermore, control of illumination is only possible by pre-adjusting the light source or using independent parameters such as cell density, and the effective irradiance cannot be adapted during cell processing. Therefore, because the actual light exposure of the cell cultures cannot be determined, prior art devices do not allow for control of the illumination of the cultures. Summary of the Invention

[0010] The present invention aims to provide an apparatus and associated method as originally specified that can illuminate a sample with controlled illumination in a reproducible and reliable manner.

[0011] This objective is achieved by the device as originally specified, which further comprises or is provided with at least one light measuring unit designed to measure the intensity of light transmitted through and / or scattered by the chemical and / or biological sample within the internal space. This means that the actual light exposure intensity of the sample can be determined and monitored, preferably in real time. This light measuring unit allows, for example, adjustment of the luminous flux (lumens, lm) and / or radiant flux (watts, W) of the illumination means, thereby precisely adjusting the light incidence and / or exposure of the sample, preferably in real time, for example, by feedback control. Feedback control can be performed as a function of the device, the vessel, or externally, for example, by a control device for the illumination means. Changes in cell number or concentration during processing, such as those caused by cell growth or medium addition, removal, or evaporation, can lead to changes in the light distribution within the vessel, which in turn changes the light exposure of the chemical and / or biological sample itself, which can be detected by the light measuring unit. Furthermore, chemical conditions such as pH and dissolved gas concentration can alter the distribution of light over time through changes in absorption at specific wavelengths due to interactions with components of the chemical and / or biological sample, such as medium components or the cells themselves. These measurements can be used to adjust the intensity of light emitted by the illumination means to compensate for changes in light scattering or transmission in the sample itself, with particular attention paid to the specific illumination wavelength employed. Furthermore, the measurements can also be used to adapt the operating conditions of the illumination means to changes in the effective light intensity emitted by the illumination means, for example, as a result of aging or environmental factors. Therefore, the device according to the present invention advantageously includes a light measurement unit as a kind of detection device for detecting the exposure of the chemical and / or biological sample during the illumination process (e.g., optogenetic control, photoactivation, or photocatalysis), preferably in real time. This allows for effective control of the illumination of the sample.

[0012] Because the effective light exposure of chemical and / or biological samples is affected by changes in the optical properties of the cell-bearing medium at the wavelengths of light used to control cellular or biochemical processes, measuring the effective light exposure and translating it into adjustments to light input intensity is particularly beneficial. Such changes in light effects can be caused, for example, by a complex interplay of increased light density and light scattering due to cell growth, the production of optically active metabolites, or chemical components in the medium changing their optical transmission properties (e.g., in response to changes in pH or dissolved gas concentrations). In many cases, it is beneficial to induce optogenetic control, photoactivation, or photocatalysis quantitatively, rather than just qualitatively, by inducing it in an on / off manner. The intensity of light reaching the reaction volume or cells determines the rate of photochemical reactions or the proportion of photoactive molecules, and therefore undergoes transitions such as photoactivation states directly. Therefore, it can be directly used to quantitatively control desired outcomes. In particular, the outcome of cellular responses using optogenetic control can be quantitatively controlled by the overall level of light exposure to the cells, particularly exposure time and intensity [2]. Therefore, for cells equipped with optogenetic light switches, the effective light exposure intensity is a key determinant for achieving the desired quantitative effect.

[0013] For example, the device according to the invention may consist of or be a container, a plurality of containers, a vessel, an enclosure, a box, a photoreactor, or a bioreactor for containing chemical and / or biological samples. The device is preferably designed with a light-tight body or other light-protecting features. At least one window for observing and / or illuminating the interior space may be disposed in the wall element and / or light-tight material.

[0014] The vessel can be, for example, a cell culture vessel or a component thereof, such as a multi-well plate, dish, lid, flask, culture bag, liner, bioreactor, or the like.

[0015] A light measurement unit is a light detection device designed and / or equipped to measure and / or record the intensity of light to which a chemical and / or biological sample is exposed. A light measurement unit according to the present invention is designed to detect and measure the amount (quantity) of light striking its light-receiving surface, similar to a light meter. For example, the light measurement unit may include at least one element selected from the group consisting of a photodiode, a light-dependent resistor, a light tube, a CMOS chip, and a solar cell. The light-dependent resistor may be, for example, a cadmium sulfide resistor with broad spectral sensitivity, which avoids the need for selecting a light intensity range with a nonlinear response curve, or a silicon-based resistor with specific sensitivity in the red and far-infrared spectrum. A light measurement unit according to the present invention does not include a spectrometer or other device that separates and measures spectral components of visible light, such as a device that can separate white light to measure individual color bands (spectra). However, the light measurement unit may also include at least one optical filter and / or at least one multiplexed detector element, preferably at least one light color / wavelength-selective photodiode. For example, the light measurement unit may be comprised of a photodiode or photoresistor combined with an optical filter to limit the spectral sensitivity of the detector to desired (e.g., chemically and / or biologically active) wavelengths. The light measurement unit may further include at least one optical recording device (e.g., memory) for recording light intensity data measured by the light measurement unit. Alternatively, or in addition, the light measurement unit may be coupled or connected to at least one external optical recording device (e.g., external memory) for recording light intensity data measured by the light measurement unit.

[0016] For example, the illumination means, the interior space and / or container, and the light measurement unit can be arranged in a straight line, with the interior space and / or container being positioned between the illumination means and the light measurement unit, which arrangement ensures that the light measurement unit captures light that has passed through the transparent or partially transparent chemical and / or biological sample.

[0017] Alternatively, a light measuring unit or light detection assembly consisting of at least two light measuring units may be arranged in relation to the illumination means at an angle approximately perpendicular to the interior space and / or container, or at an acute angle to the interior space and / or container, preferably less than 20°, more preferably less than 10°.

[0018] Relative to the illumination means, the light measurement unit may be positioned, for example, at or near 180° to the interior space and / or container (e.g., a transparent or partially transparent sample). Alternatively, or in addition, the light measurement unit may be positioned at an angle formed between the illumination means, the chemical and / or biological sample, and the light measurement unit. For example, at an angle of approximately 90°, the light measurement unit captures light scattered laterally within the chemical and / or biological sample. Alternatively, by forming an acute angle between the illumination means, the chemical and / or biological sample, and the light measurement unit, the light measurement unit captures light scattered backward within the chemical and / or biological sample. At an angle between 90° and 180°, the light measurement unit captures light scattered forward within the chemical and / or biological sample. At these intermediate angle positions, the light measurement unit captures a mixture of transmitted and scattered light.

[0019] In an advantageous embodiment of the invention, the light measuring unit comprises at least one light receiving surface, the illuminance [lux, lx] and / or irradiance [W / m 2 Thus, it is possible to measure the intensity of light emitted by the illumination means as it passes through and / or is scattered during passage through a chemical and / or biological sample (exposure over time).

[0020] In a further advantageous embodiment of the present invention, the device and / or the light measurement unit may comprise at least one optical filter element. That is, the device and / or the at least one light measurement unit may comprise different filters for detecting light of different wavelengths. Thus, the device according to the present invention may measure specific wavelengths using optical filters and / or multiple light measurement units, e.g., light color / wavelength selective photodiodes, for example, to measure the light intensity at chemically and / or biologically active wavelengths.

[0021] In another advantageous embodiment of the invention, two or more lighting means are provided, for example the lighting means may consist of two or more light emitting elements such as light emitting diodes (LEDs).

[0022] In another advantageous embodiment of the invention, the light measuring unit is part of a light detection assembly which consists of at least two light measuring units, for example the light detection assembly can consist of two or more photodiodes.

[0023] To hold at least one chemical and / or biological sample, the device or container may be comprised of two or more cavities designed to receive the sample(s).

[0024] At least one light measurement unit and at least one illumination means may be arranged in an aligned configuration. For example, if a container is provided that consists of two or more internal spaces or two or more cavities, each internal space or each cavity of the container can be arranged between the illumination means and the light measurement unit. This arrangement ensures that, if the internal space or cavity and the sample are transparent or partially transparent, each light measurement unit can capture light that has passed through the sample arranged between the aligned illumination means and the light measurement unit. Thus, the device according to the present invention can be arranged to maximize detection of light from the primary direction of the light source used to illuminate the sample. That is, the direction of maximum sensitivity of the light measurement unit(s) is at least approximately oriented toward the light source (illumination means). When the light measurement unit is aligned with a multi-sample container, e.g., a multi-well plate, the light measurement unit can detect the exposure of each individual sample.

[0025] In a preferred embodiment, at least one blind element is arranged between the aligned light measuring units and the lighting means, the blind element comprising at least one opening. The blind element captures only light from the respective light measuring unit aligned with the lighting means, as this concentrates the light beam and reduces light scattering. This can be achieved, if the appropriate geometry is taken into account, for example, by a perforated plate with or without a lens.

[0026] In another advantageous embodiment of the invention, the light measurement unit comprises or is coupled to at least one control element. The control element is preferably configured to control the illumination of the illumination means and / or the chemical and / or biological sample in the interior space or to measure and / or record the exposure dose of the chemical and / or biological sample in the interior space. The control element may comprise a circuit capable of recording or processing data regarding the exposure over time, while the light measurement unit detects the exposure of the chemical and / or biological sample, preferably in real time, during optogenetic control, photoactivation, or photocatalysis.

[0027] In a particularly advantageous embodiment of the present invention, the light measurement unit comprises or is coupled to at least one control device for adjusting the color and / or light transmittance of the switchable element. For example, the interior space can be at least partially enclosed by at least one wall element and protected from light intrusion by at least one light-blocking material, except for at least one window for observing and / or illuminating the interior space. The window can comprise at least one switchable element whose color and / or light transmittance can be switched. That is, the switchable element allows the window to be easily switched between a first state ("closed state") in which light is blocked from the interior space and at least a second state ("active state") in which light can enter and exit the interior space through the window in a controlled manner. Light exposure of chemical and / or biological samples in the interior space can be controlled by the switchable element, thereby avoiding unintended light exposure during "off phases" (i.e., when the sample is not illuminated or when the sample is being prepared, stored, or transported) and adjusting light exposure during "on phases" (i.e., when the sample is illuminated). The switchable element can be designed to change color and / or increase transmittance and / or transparency when switched from a first state to a second state. In the first state ("closed"), the element is energetically neutral and powered off, thus enabling non-wired light protection during transport or storage of the device. In the second state ("active"), a user or device can "open the shade" to allow visual inspection or electromagnetic irradiation of chemical and / or biological samples contained within the device's interior space. Outside of a specific environment where controlled illumination occurs, the window blocks light intrusion, or at least certain chemically or biologically active wavelengths, protecting the chemical and / or biological material from unintended illumination, such as from ambient light or sunlight exposure. Thus, such a switchable element allows for easily controlled protection of the interior space before and / or after illumination, even after removal or disassembly from the lighting device.It also allows for easy, controlled observation of the interior space before, during, and / or after illumination without disassembling the entire device. In advantageous embodiments, the controller may be configured to trigger such switchable elements to control light exposure to chemical and / or biological samples within the interior space, preferably via real-time feedback control.

[0028] In one advantageous embodiment of the present invention, the light measurement unit is configured with or connected to at least one feedback control system (circuit) and / or at least one analog control device to detect the light intensity and intensity difference of the illumination means, or the light intensity and intensity difference between at least one illumination means and at least one reference (predefined or internal). The feedback control system and / or analog control device can be used to regulate or adjust the intensity of the illumination means (e.g., the number of powered-on independent light sources (e.g., LEDs)) and / or the time schedule (e.g., pulse-width modulation of the light-emitting units and / or powering on with an on / off pulse or similar schedule). In this embodiment, the light intensity and intensity difference can be detected over time for light generated by the illumination means and transmitted through (transmitted by) the chemical and / or biological sample, or light generated by light scattering in the chemical and / or biological sample, depending on the spatial arrangement of the illumination means and the light metering unit relative to the chemical and / or biological sample. The transmittance and / or light scattering within the material and / or biological sample can be used by a control system to adjust the intensity and / or time schedule so that the effective average light exposure to any subvolume of the chemical and / or biological sample remains constant as optical properties such as absorbance characteristics or concentrations such as particle size or cell density change over time. In the case of bioreactors or other cell containers where the chemical and / or biological sample is shaken, moved, stirred, or otherwise agitated and continuously moving within the container, this adjustment of the emitted light intensity ensures that all subvolumes and / or cells within the sample are exposed to a constant average light intensity over time.

[0029] For example, the device according to the present invention can consist of or be a container, a plurality of containers, a vessel, an enclosure, a box, a photoreactor, or a bioreactor for containing chemical and / or biological samples. The device is preferably designed with a light-tight body or other light-protecting features. In a preferred embodiment, the illumination means and the light measurement unit are arranged between the (light-tight) body and the vessel. In another preferred embodiment, at least one window for observing and / or illuminating the interior space can be arranged in the wall element and / or the light-tight material. The device can be combined with a switchable element designed to change color and / or transmittance and / or transparency in response to a signal sent from the device that actively opens the window for optical access to the sample in a second state and closes the window in a first state. Desirably, the switching is achieved in response to an electrical signal applied by the device's electronics (e.g., at least one control unit). The switchable element is part of or attached to a light panel of the lighting means and / or is attached to the wall of a container, enclosure or box containing the chemical and / or biological sample itself (e.g., preferably the bottom or top of a cell culture plate, cell culture bag, flask, or wall of a bioreactor).

[0030] For example, the light measurement unit can detect light from a 360-degree solid angle, or it can include two detection units on a single plane that collect light from a half-space or a solid angle close to 180 degrees, ensuring light capture from two antipodal directions. Furthermore, the light measurement unit can include a hemispherical collector to increase sensitivity to light incident from an acute angle with the plane defined by the two detection units, or six detection units can be arranged in a cube to collect light from a half-space or achieve coverage of a solid angle close to 180 degrees, ensuring 360-degree or close to 360-degree detection. The light measurement unit may further include a detection unit that is a bioreactor and / or cell culture cabinet-compatible light meter, preferably sealed or lacquered to prevent liquids and moisture. In advantageous embodiments, the light measurement unit is autonomous in terms of energy supply or data collection (memory), and thus can independently detect light and transmit information wirelessly to an electronic device, eliminating the need for a wired connection. The light measurement unit may be powered by a preferably long-life internal battery, by energy transmitted electromagnetically in non-contact mode from the outside, and / or by light exposure alone, e.g., by a photodiode that converts light into electrical current, thereby providing energy to detect light exposure and record, process, or transmit data related to the exposure. The light measurement unit may further be equipped with a data storage unit for wireless operation and later data transfer to another system (e.g., a computer) for analysis.

[0031] A device according to the invention may contain multiple independent chemical and / or biological samples in separate containers or in separate regions of one or more containers (e.g., wells of a multiwell plate or spots of a microarray / biochip), where one switchable element and / or optical shutter controls the incidence of light to all samples simultaneously. Preferably, fewer switchable elements than samples control the incidence of light to the samples. Alternatively, the same number of switchable elements control the incidence of light to each sample individually.

[0032] This object is further achieved, as initially specified, by a method for controlling the exposure of at least one chemical and / or biological sample to light, wherein the intensity of light transmitted through or scattered by the chemical and / or biological sample in an internal space is measured by at least one light measuring unit which measures the intensity of light at biologically and / or chemically active wavelengths. According to the invention, the intensity to which the sample is actually exposed to light or the intensity of light transmitted or scattered by the sample is measured, preferably in real time. For this purpose, the at least one light measuring unit preferably measures the illuminance [lux (Lux, lx)] and / or irradiance [watts per square meter (W / m )] of its light receiving surface. 2The illuminating means is designed to measure the light intensity (lumens, lm) and / or radiant flux (watts, W) of the illumination means, which allows the intensity of light transmitted through or scattered within a chemical and / or biological sample to be determined (light exposure over time). Based on the light intensity detected by at least one light measuring unit, the luminous flux (lumens, lm) and / or radiant flux (watts, W) of the illumination means can be adjusted, thereby precisely controlling the light penetration into and / or exposure of the sample, preferably via feedback control. This allows the effects of absorbance and / or light scattering over time in biological / chemical samples to be compensated for by adjusting the luminous flux and / or radiant flux of the illumination means. These changes in light absorption and / or light scattering typically result from the ongoing cell culture process, which increases the concentration of live and dead cells. They can also result from changes in medium composition or pH over time, or from the addition of medium or additives, or the removal of medium, products, or cells during the cell culture process. The illumination itself can induce photochemical or photophysical changes in the sample, which require the adjustment of the luminous flux and / or radiant flux of the illumination means to adjust the average effective exposure of a representative subsample or cell within the sample, respectively. For example, if the absorbance and / or scattering of light emitted from the illumination means increases over time, e.g., as a result of increasing cell density, the light output of the illumination means can be increased, e.g., by increasing the number of powered light-emitting elements, changing the pulse-width modulation parameters of the light-emitting elements, or changing their on / off time schedules. Feedback control can be performed as a function of the device, the vessel, or externally, e.g., by a control device for the illumination means. Furthermore, the light intensity data measured by the light measurement unit can be recorded by at least one optical recording device (e.g., memory). The optical recording device can be an integrated part of the light measurement unit (e.g., as an internal memory) or can be coupled or connected to the light measurement unit (e.g., as an external memory).Therefore, an advantage of the method according to the present invention is that the effective light exposure of chemical and / or biological samples can be detected, recorded and analyzed in real time during the process of illumination (e.g., optogenetic control, photoactivation or photocatalysis), allowing for effective control of sample illumination.

[0033] In an advantageous embodiment of the method according to the invention, measuring the light intensity is determined by measuring the illuminance [lx] and / or the irradiance [W / m 2 ] at at least one light receiving surface of the light measuring unit, i.e. the intensity of the light emitted by the illumination means passing through and / or scattered as it passes through the chemical and / or biological sample can be determined.

[0034] In another advantageous embodiment of the method according to the invention, the light intensity is measured over time by at least one optical recording device, which may be an integrated part of the light measurement unit (e.g. as an internal memory) or may be coupled or connected to the light measurement unit (e.g. as an external memory) in order to allow recording and / or documentation of the light intensity during the illumination process.

[0035] In an advantageous embodiment of the method according to the invention, at least one illumination intensity profile and / or spectral characteristics (quality) are recorded in real time by an optical recording device, which can be used to record the actual intensity, wavelength characteristics or light dose of the intended illumination, as well as any unintended light contamination that occurs during the process (e.g. due to exposure to ambient light or a malfunction of the illumination means).

[0036] Preferably, the measured light intensity values are used to compensate or adjust in real time the intensity of the light emitted by the lighting means. For example, a fluctuation or change in at least one peak wavelength in the spectrum of the lighting means may be detected to detect aging or degradation of the lighting means, e.g., for initiating repairs or end-of-life notification. In such an embodiment, the intensity of the light emitted by the lighting means (e.g., luminous flux and / or radiant flux) may be automatically and / or electronically adjusted (recalibrated) in response to the detected fluctuation or change. Alternatively, if the aging or degradation exceeds a predetermined predefined value, this diagnosis may be reported to the system user or technical service.

[0037] The calibration method for an optogenetic lighting device, as originally defined, also achieves this objective by determining at least one measured value of at least one functional parameter of a lighting means, comparing it with at least one measured value of the same functional parameter of at least one other lighting means, a previously recorded value of the same lighting means, or at least one preset and / or standard value, and determining and documenting the difference values resulting from the comparison. Thus, "factory" differences in the light output of lighting means, such as light-emitting elements, and other variations resulting from their aging or other manufacturing or geometric deviations, can be equalized by a control system, for example, by adjusting or offsetting the individual currents and / or voltages of the light-emitting elements (e.g., LEDs) or by pulse-width modulation. This method can be employed, for example, by at least one control system (circuit) or at least one analog control device. The control system or analog device can perform offline (during a calibration routine when no sample or specimen is loaded) or real-time (during a procedure when the sample or specimen is illuminated) calibrations between individual lighting means or against preset or standard values within or independent of the lighting device. Desirably, this procedure is performed without any chemical and / or biological sample or specimen loaded and throughout the illumination process, allowing adjustments to be made for the transmittance and / or light scattering properties of the chemical and / or biological sample as they change over time.

[0038] In an advantageous embodiment of the method, the determination and comparison of the measurements of the functional parameters is performed offline, preferably during a calibration routine without a sample or specimen being loaded, or in real time during a procedure in which the sample or specimen is irradiated or irradiated.

[0039] As used herein, the terms "illumination" or "under illumination" refer to the application of light to a space, object, or sample, including, but not limited to, the active treatment of a space, object, or sample with light, or the passive exposure of a space, object, or sample to light (including visual inspection or analysis of the space, object, or sample).

[0040] As used in this document, "light" refers to electromagnetic radiation of all wavelengths, including visible and invisible light, gamma rays, X-rays, microwaves, and radio waves. Visible light has wavelengths in the 400-700 nanometer (nm) range, i.e., radiation between infrared and ultraviolet. Infrared (IR) radiation has longer wavelengths than visible light, ranging from 700 nanometers to 1 millimeter. Ultraviolet (UV) radiation has shorter wavelengths than visible light and longer than X-rays, ranging from 10 nm to 400 nm.

[0041] "Light intensity" or "luminous intensity" is used herein as an undefined (indefinite) generic term that refers to the amount or quantity of light, and includes specific radiometric and photometric values that define the amount of light (e.g., illuminance, irradiance, luminous flux, radiant flux, exposure dose, radiant exposure, etc.).

[0042] As used herein, "light effect" or "effective exposure" refers to the amount or intensity of light (light intensity) that actually strikes the surface of an object, cell, or molecule, i.e., the intensity to which the object, cell, or molecule is actually exposed under operating conditions.

[0043] As used herein, "color" refers to the physical property of a translucent material's differential transmittance for different wavelengths of the light spectrum, i.e., its wavelength selectivity, and also refers to light that has passed through the material and, as a result, has a shifted wavelength spectrum compared to the incident light.

[0044] As used herein, "transmittance" or "light transmittance" refers to the physical property of light passing through a material, without wavelength selectivity, similar to a neutral density filter. As used herein, "transmittance" includes both "transparency" and "translucency." Transparency is the physical property of allowing light to pass through a material with little or no scattering. Translucency (semi-transparency) is the physical property of allowing light to pass through a material, but the light is scattered due to changes in refractive index within or at the surface of the material. [Brief explanation of the drawings]

[0045] [Figure 1] FIG. 1 shows a schematic view (longitudinal section) of an exemplary embodiment of a device according to the invention, where the device is a multi-well plate. [Figure 2] FIG. 2 is a schematic diagram (longitudinal cross section) of another exemplary embodiment of a device according to the invention, in which a multiwell plate is placed within the device. [Figure 3] FIG. 3 is a schematic view (longitudinal section) of a further exemplary embodiment of the device according to the invention, comprising lighting means, in which a cell culture flask is placed in the device. [Figure 4] FIG. 4 shows a schematic view (longitudinal section) of a further exemplary embodiment of the device according to the invention, equipped with lighting and ventilation means, in which a multiwell plate is placed. [Figure 5] FIG. 5 shows a schematic view (longitudinal section) of a further exemplary embodiment of the device according to the invention, equipped with lighting and ventilation means, with a flask or bioreactor placed inside the device. [Figure 6]6 shows a schematic diagram (cross section) of a further exemplary embodiment of a device according to the invention, comprising illumination and light measurement means, which device is integrated into a bioreactor. DETAILED DESCRIPTION OF THE INVENTION

[0046] FIG. 1 shows an exemplary embodiment of a device 1 according to the present invention. The device 1 is composed of a number of cavities 2 ("wells"), each representing an internal space 3 capable of containing a chemical and / or biological sample 13. Each cavity 2 / internal space 3 is partially surrounded by a wall element 4, which is open at the top of each internal space 3. At the bottom of each internal space 3, the wall element 4 defines a window 5 for observing and / or illuminating the internal space 3. The chemical and / or biological sample 13 can be introduced into the internal space 3 through an opening 6. The opening 6 is covered by a lid 7 that extends to all cavities 2. To protect the internal space 3 from light intrusion, the wall element 4 and the lid 7 are made of a light-blocking material. Each window 5 is either permanently transparent or is composed of at least one switchable element 8 whose color and / or light transmittance are switchable. Each switchable element 8 is switchable between a first state (a "closed state") and one or more second states ("active states"). In the closed state, light is blocked from the interior space 3, whereas in the active state, light can enter and exit the interior space 3 in a controlled manner through the window 5. In this way, the switchable elements 8 allow control of light exposure to the chemical and / or biological sample 13 in the interior space 3 of each cavity 2, effectively avoiding unintended light exposure when the sample is not illuminated and / or when the device 1 is stored or transported. Furthermore, when the sample is illuminated, the light exposure to the chemical and / or biological sample 13 in the interior space 3 can be adjusted by the switchable elements 8. In an advantageous embodiment of the present invention, it is also possible to observe the chemical and / or biological sample 13 in the interior space 3 through the "open" window 5 by switching the corresponding switchable element 8 from the closed state to the active state. Illumination of the interior space 3 is provided by an external light bar or array 9 consisting of a number of illumination means 10 (e.g., LEDs), each of which is positioned below one window 5.

[0047] A light detection assembly 11 (sensor array) consisting of multiple light measurement units 12 is disposed on the lid 7 to measure the intensity of light passing through the interior spaces 3 containing the chemical and / or biological samples 13, with one light measurement unit 12 positioned above each of the five interior spaces 3. In such an embodiment, the light-blocking material of the lid 7 must be "porous," i.e., contain holes or transparent (or at least partially transparent) sections below each light measurement unit 12, so that light passing through the interior spaces 3 and the chemical and / or biological samples 13 can be detected. The light detection assembly 11 and / or the light measurement units 12 can be coupled to control elements, which can electronically adjust / adjust the color and / or light transmittance of the switchable element 8 and / or the light bar 9 and / or the illumination means 10. According to the present invention, the light intensity actually received by the chemical and / or biological sample 13 in each cavity 2 can be determined and monitored in real time. For this purpose, each light measuring unit 12 is designed to measure the illuminance and / or irradiance of its light receiving surface, thereby making it possible to determine the intensity of light emitted by the illumination means 10 that has passed through the chemical and / or biological sample 13. The illuminance and / or irradiance values measured by the light measuring units 12 are processed and used to adjust and / or adapt the luminous flux and / or radiant flux of the illumination means 10, thereby precisely adjusting the light incidence on and / or exposure of the sample in real time. Thus, the light measuring units 12 detect the light exposure of the chemical and / or biological sample 13 in the course of illumination (e.g., optogenetic control, photoactivation, or photocatalysis) in real time and effectively control the illumination of the sample.

[0048] The illumination means 10, the internal space 3 and the light measurement units 12 are aligned such that each internal space 3 / cavity 2 is located between one illumination means 10 and one light measurement unit 12, so that each light measurement unit 12 can reliably capture light that has passed through the chemical and / or biological sample 13 in each cavity 2.

[0049] FIG. 2 shows another exemplary embodiment of a device 15 according to the present invention. The device 15 includes a wall element 17 surrounding an interior space 16, the wall element 17 being made of a light-blocking material that protects the interior space 16 from light intrusion. At the bottom of the device 15, the wall element 17 further includes a window 18 for observing and / or illuminating the interior space 16. The window 18 includes a switchable element 19 with variable color and / or light transmittance. For example, the switchable element 19 may be a liquid crystal panel or the like. The switchable element 19 can be switched between a first state (a "closed state") and one or more second states (an "activated state"). In the closed state, light is blocked from the interior space 16, while in the activated state, light can enter and exit the interior space 16 through the window 18 in a controlled manner.

[0050] The container 20 is disposed within the interior space 16 of the device 15. The container 20 is designed to contain at least one chemical and / or biological sample 28, e.g., a suspension or liquid containing living cells. The container 20 may be a standard cell culture vessel consisting of multiple cavities 21 ("wells"), such as a 6-, 12-, 24-, or 96-well plate. The cavities 21 of the container 20 are covered with a lid 22. To allow light to enter the cavities, the container 20 is constructed of a transparent or at least partially transparent material. The switchable element 19 can control the light exposure of the chemical and / or biological sample 28 (cells) within the cavity 21 of the container 20, effectively avoiding unintended light exposure when the interior space 16 is not illuminated and / or when the device 15 is stored or transported. Furthermore, when the interior space 16 is illuminated from the outside, the switchable element 19 can regulate the light exposure of the chemical and / or biological sample 28 within the container 20. In an advantageous embodiment of the invention, it is also possible to observe the cells in the container 20 through the window 18 by switching the switchable element 19 from a closed state to an active state. Illumination of the interior space 16 is provided by an external light source, bar or array 23 consisting of at least one lighting means 24 (e.g., LEDs) arranged below the switchable element 19. The switchable element 19 is coupled to an electronic control unit (not shown) via contact elements 25 so that it can be easily switched between the closed and active states. If the switchable element 19 is made of an electrochromic material, the desired state transition can be induced by passing an electric current through the material via the contact elements 25.

[0051] At least one light measuring unit 26 is attached to the underside of the upper end of the wall element 17 within the interior space 16 to measure the intensity of light passing through the interior space 16. Either a single light measuring unit 26 or, as shown, a light detection assembly 27 (sensor array) consisting of multiple light measuring units 26 is provided. In this embodiment, the lid 22 must be constructed of a transparent or at least partially transparent material, or at least "porous," i.e., contain holes beneath each light measuring unit 26. This allows for detection of light passing through the cavity 21 and the chemical and / or biological sample 28. The light detection assembly 27 and / or light measuring unit 26 can be coupled to a control element, which can electronically adjust / adjust the color and / or light transmittance of the switchable element 19 and / or light bar 23 and / or lighting means 24. According to this invention, the actual light intensity received by the chemical and / or biological sample 28 in each cavity 21 can be determined and monitored in real time. For this purpose, each light measurement unit 26 is designed to measure the illuminance and / or irradiance of its light-receiving surface, thereby determining the intensity of light emitted by the illumination means 24 that has passed through the chemical and / or biological sample 28. The illuminance and / or irradiance values measured by the light measurement units 26 are processed and used to adjust and / or adapt the luminous flux and / or radiant flux of the illumination means 24, thereby precisely adjusting the light incidence on and / or exposure to the sample 28 in real time. Thus, the light measurement units 26 detect the light exposure of the chemical and / or biological sample during the illumination process (e.g., optogenetic control, photoactivation, or photocatalysis) in real time and effectively control the illumination of the sample 28. To ensure that each light measurement unit 26 can capture the light that has passed through the chemical and / or biological sample 28 in each cavity 21, the illumination means 24, the cavities 21, and the light measurement units 26 are aligned so that each cavity 21 is located between the illumination means 24 and one light measurement unit 26.

[0052] FIG. 3 illustrates a further exemplary embodiment of a device 30 according to the present invention. The device 30 comprises an interior space 31 surrounded by a wall element 32 made of a light-blocking material that protects the interior space 31 from light intrusion. In this advantageous embodiment, the wall element 32 includes two portions 33, 34 attached to each other by at least one interconnectable connecting structure 35, which define a light-tight, gas-permeable opening 36 that allows ventilation of the interior space 31 while preventing external light from entering the interior space 31. In this embodiment, the opening 36 is a serpentine channel. At the bottom of the device 30, the wall element 32 further comprises a window 37 for observing and / or illuminating the interior space 31. The window 37 comprises a switchable element 38 with variable color and / or light transmittance. For example, the switchable element 38 may be an LCD panel or the like. The switchable element 38 can be switched between a first state (a "closed state") and one or more second states ("activated states"). In the closed state, light is blocked from the interior space 31, whereas in the activated state, light can enter and exit the interior space 31 through the window 37 in a controlled manner.

[0053] The container 39 is disposed within the interior space 31 of the device 30. The container 39 is designed to contain at least one chemical and / or biological sample 45, e.g., a suspension or liquid containing living cells. The container 39 may be a standard cell culture flask made of an at least partially transparent or at least partially transparent material. The switchable element 38 allows for control of light exposure of the chemical and / or biological sample 45 (cells) within the container 39, effectively avoiding unintended light exposure when the interior space 31 is not illuminated and / or when the device 30 is stored or transported. Furthermore, when the interior space 31 is illuminated from the outside, the switchable element 38 allows for adjustment of light exposure of the chemical and / or biological sample 45 within the container 39. In an advantageous embodiment of the present invention, it is also possible to observe the cells within the container 39 through the window 37 by switching the switchable element 38 from a closed state to an active state. The device 30 is coupled to an external illumination unit 40, which consists of a light source, bar or array 41, a control element 42, and a power source 43. The light bar 41 consists of a plurality of lighting means 44 (e.g., LEDs) arranged under the switchable element 38 to illuminate the interior space 31. In this embodiment, the electrical connection between the external lighting unit 40 and the device 30 is established by at least one electrical contact unit 46, such as a spring contact or at least one pair of plug-and-socket matings, with at least two conductors establishing electrical contact. This allows electrical energy to be supplied from the power source 43 to elements installed in the device 30, such as the light measurement unit 47 and the interior space ventilation fan (not shown in FIG. 3 ). Furthermore, electrical signals can be transmitted from the light measurement unit 47 and other sensors to the control element 42, or from the control element 42 to the switchable element 38. In this embodiment, the electrical contact unit(s) 46 allow easy and reversible detachment of the top of the device 30 from the external lighting unit 40. The external lighting unit 40 serves as a docking station for the device 30, representing a portable light protection and illumination chamber.

[0054] A light measurement unit 47 is attached to the underside of the upper surface of the upper portion 33 of the wall element 32 within the interior space 31 to measure and record the intensity of light passing through the interior space 31 and thereby the container 39 and the chemical and / or biological sample 45 contained therein (e.g., a cell suspension or culture medium containing cells attached to and growing on the walls of the container 39). The switchable element 38 and / or the illumination means 44 can be controlled by the control element 42, while information from the light measurement unit 47 can be used by the control element 42 to determine the state of the switchable element 38 and / or the illumination means 44. The light measurement unit 47 measures the light exposure of the chemical and / or biological sample 45 in real time during the process of illumination (e.g., optogenetic control, photoactivation, or photocatalysis), thereby providing light intensity data to the control element 42, which can effectively control the illumination of the sample 45.

[0055] FIG. 4 illustrates a further exemplary embodiment of a device 60 according to the present invention. The device 60 includes a wall element 62 surrounding an interior space 61, the wall element 62 being made of a light-blocking material that prevents light from penetrating into the interior space 61. In this advantageous embodiment, the wall element 62 includes two sections 63, 64 attached to each other by at least one interconnectable connecting structure 65 that includes at least one light-tight but gas-permeable opening 66 that prevents external light from entering the interior space 61 while allowing passive ventilation of the interior space 61. In this embodiment, the opening 66 is a serpentine channel. A partition plate 67 is disposed within the interior space 61 and divides the interior space 61 into a lower interior space 68 and an upper interior space 69. The partition plate 67 is made of a light-blocking material and includes at least one or more windows 70 for observing and / or illuminating the upper interior space 69. Each window 70 comprises a switchable element 71 with variable color and / or light transmittance, which is positioned beneath or in the opening of the divider 67 in the lower interior space 68. For example, each switchable element 71 may comprise an optical layer made of an electrochromic material (e.g., tungsten trioxide) that converts non-absorbing molecules to a light-absorbing state and vice versa through a redox reaction. While a current can be applied to the material to induce these transitions, it is not required to maintain the material's state; thus, they have a memory effect. Thus, each switchable element 71 comprises an electrochromic optical layer that can be independently switched between an opaque and a transparent state by applying a lower voltage. In the opaque state, light is blocked from the upper interior space 69, whereas in the transparent state, light can enter and exit the upper interior space 69 in a controlled manner through the window 70.

[0056] Containers 72 are arranged on a divider plate 67 within the upper interior space 69 of the device 60. The containers 72 are designed to contain at least one chemical and / or biological sample 88, e.g., a suspension or liquid containing live cells. The containers 72 may be standard cell culture vessels, e.g., 24- or 96-well plates, consisting of multiple cavities 74 ("wells"). The cavities 74 of the containers 72 are covered by a lid 75. Illumination of the upper interior space 69 is provided by an internal light source assembly, bar, or array 76 consisting of multiple lighting means 77 (e.g., LEDs). The internal light source assembly 76 is arranged below the switchable element 71 within the lower interior space 68, and the lighting means 77 are aligned below the window 70. In an advantageous embodiment of the invention, the lighting means 77 are optically separated from each other by wall elements 89, which prevent light from non-aligned lighting means 77 from entering the window 70. In this way, it is possible to mutually and independently illuminate each cavity 74 and each chemical and / or biological sample 88 in the container 72 through only one illumination means 77. The light exposure of the chemical and / or biological sample (cells) 88 in each cavity 74 of the container 72 can be independently adjusted by the corresponding switchable element 71 when the upper interior space 69 is illuminated by the illumination means 77. In an advantageous embodiment of the invention, it is also possible to observe the cells in the container 72 with at least one camera (not shown) through the window 70 by switching the switchable element 71 from an opaque state to a transparent state.

[0057] To measure the intensity of light passing through the upper interior space 69, a light detection assembly 78 (sensor array) consisting of multiple light measurement units 79 is attached to the underside of the upper surface of the upper portion 63 of the wall element 62 within the upper interior space 69. A light blocking element 86 is arranged between the light detection bar 78 and the illumination means 77, and thus between the containers 72, and the light blocking element 86 is composed of multiple openings 87. The light blocking element 86 is thus a kind of perforated plate that allows light to pass through the openings 87. Because the light beam is focused at the openings 87 and light scattering is reduced, the light blocking element 86 ensures that light is captured only by the individual light measurement units 79 aligned with each cavity 74 of the container 72 and each illumination means 77.

[0058] The device 60 further includes a cooling unit 80 for passive or active cooling of the interior space 61 and a fan 81 for active ventilation of the upper interior space 69. The cooling unit 80 is located on the exterior of the device 60, above the upper portion 63 of the wall element 62. The cooling unit 80 can be a heat sink for passive cooling, such as a metal body with cooling fins, or an active cooling assembly, such as a thermoelectric element connected on one side to the upper or lower wall element 63 or 64 and on the other side to a heat sink. In additional embodiments, it can be connected to a water-based cooling system (not shown). This cooling unit maintains a desired temperature within the upper interior space 69 and prevents uncontrolled overheating due to heat sources, such as the light source assembly 76, located within or connected to the device 50. The fan 81 is located within a first vent 82 in the upper interior space 69, which is covered by a breathable first filter element 83 designed to prevent contamination of the interior space 61. At least one of the fan 81 and the filter element 83 is light-tight to protect the interior space 61 from light intrusion. For pressure compensation, a second vent 84 is located opposite the first vent 82. The second vent 84 is equipped with a second filter element 85 that is light-tight but air-permeable, designed to prevent contamination of the interior space 61. This active ventilation system makes it possible to maintain optimal conditions for culturing, for example, live cells, in the upper interior space 69, for example, when the device 60 is placed in a cell culture incubator that provides an atmospheric environment with controlled gas composition, temperature, and humidity.

[0059] FIG. 5 illustrates a further exemplary embodiment of a device 100 according to the present invention. The device 100 includes a wall element 102 surrounding an interior space 101, the wall element 102 being made of a light-blocking material that prevents light from penetrating into the interior space 101. In this advantageous embodiment, the wall element 102 includes two parts 103, 104 attached to each other by at least one interconnectable connecting structure 105 that define a light-tight, gas-permeable opening 106 that prevents external light from entering the interior space 101 while allowing ventilation of the interior space 101. In this embodiment, the opening 106 is a serpentine-shaped channel. At the bottom of the device 100, the wall element 102 further includes a window 107 for observing and / or illuminating the interior space 101. The window 107 includes a switchable element 108 with variable color and / or light transmittance. For example, the switchable element 108 may be a liquid crystal display panel or the like. The switchable element 108 can be switched between a first state (a "closed state") and one or more second states (an "activated state"): in the closed state, light is blocked from the interior space 101, whereas in the activated state, light can enter and exit the interior space 101 through the window 107 in a controlled manner.

[0060] The container 109 is disposed within the interior space 101 of the device 100. The container 109 is designed to contain at least one chemical and / or biological sample 110, e.g., a suspension or liquid containing living cells. The container 109 is a standard cell culture flask or bioreactor and is at least partially transparent or made of an at least partially transparent material. The switchable element 108 allows for control of light exposure of the chemical and / or biological sample 110 (cells) within the container 109, such that unintentional light exposure can be effectively avoided when the interior space 101 is not illuminated and / or when the device 100 is stored or transported. Furthermore, when the interior space 101 is illuminated from the outside, the switchable element 108 allows for adjustment of light exposure of the chemical and / or biological sample 110 within the container 109. In an advantageous embodiment of the present invention, it is also possible to observe cells within the container 109 through the window 107 by switching the switchable element 108 from a closed state to an active state. The device 100 is coupled to an external lighting unit 120 consisting of a light source, bar or array 121, a control element 122, and a power supply 123. The light source assembly 121 consists of a plurality of light emitting elements 124 (e.g., LEDs) positioned below the switchable element 108 to illuminate the interior space 101. In this embodiment, the electrical connection between the external lighting unit 120 and the device 100 is established by a contact 125 having at least two wires, such as a spring contact or a matching pair of contacts in a plug and socket.

[0061] A light measurement unit 111 is attached to the underside of the upper surface of the top portion 103 of the wall element 102 within the interior space 101 in order to measure and record the intensity of light passing through the interior space 101 and thus through the container 109 and the chemical and / or biological sample 110 contained therein (e.g., a cell suspension or culture medium containing cells growing attached to the wall of the container 109). A second light measurement unit 112 is attached to the wall element 102 in a configuration to measure the scattering of light in a direction perpendicular to the direction of light emitted by the light source assembly 121. The switchable element 108 and / or the lighting means 124 can be controlled by a control element 122, while information from the light measurement units 111 and / or 112 can be used by the control element 122 to determine the state of the switchable element 108 and / or the lighting means 124. Light measurement units 111 and / or 112 not only measure the light exposure of chemical and / or biological sample 45, but also measure in real time its optical properties, which change the light transmission of the chemical and / or biological sample itself during the course of illumination (e.g., optogenetic control, photoactivation, or photocatalysis). Control element 122 can receive and process this data and use this information to effectively control illumination means 124, and thereby control illumination of biological sample 110.

[0062] The device 100 further comprises a vent 125 equipped with a light-tight but air-permeable filter element 126 designed to avoid contamination of the interior space 101. This passive ventilation system allows optimal conditions to be maintained within the interior space 101 and / or container 109, for example for culturing living cells, such as when the device 100 is placed in a cell culture incubator that provides an atmospheric environment with controlled gas composition, temperature and / or humidity.

[0063] The device 110 can be mounted on a shaker (not shown) to allow for agitation of the chemical and / or biological sample 110 within the container 109 (e.g., a shaker flask). Alternatively, the device 110 can provide a means for connecting the container 109 or interior space 101 to an external source or additional measurement means (e.g., a medium supply line, connection to a biochemical or physical sensor (not shown)).

[0064] FIG. 6 illustrates a further exemplary embodiment of a device 130 according to the present invention. The device 130 comprises a carrier 134 equipped with a light-emitting element 135 that illuminates an interior space 133 that can accommodate a container, liner, or bag 132 for containing a biological or chemical sample, such as cultured cells in a medium. The carrier 134 is further surrounded and held by a light-tight container 131, such as a steel tank for a bioreactor, that prevents light from entering from outside and holds the carrier 134. The carrier 134 can be mechanically flexible to accommodate the shape formed between the light-tight container 131 and the container, liner, or bag 132. Alternatively, the carrier 134 can be attached to the light-tight container 131. The carrier 134 can also be composed of multiple panels connected to each other via hinges, allowing the carrier to adjust to the curvature of the interior wall of the light-tight container 131. The carrier 134 further comprises light-measuring units 137, 138, and 139 positioned at a fixed angle toward a light-emitting element 136 that is controlled independently of the other light-emitting elements 135. In this example, the light measuring unit 137 is disposed so that the angle formed between the light emitting element 136, the center of the internal space 133, and the light measuring unit 137 is approximately 180°. The light measuring unit 137 can be used to preliminarily measure the transmittance of light emitted from the light emitting element 136 and passing through the internal space 133. Another light measuring unit 138 is disposed at an angle of approximately 90° formed between the light emitting element 136 and the center of the internal space 133. The light measuring unit 138 can be used to preliminarily measure the side scattering of light emitted from the light emitting element 136 and passing through the internal space 133. A third light measuring unit 139 is disposed at a very small angle (preferentially less than 20°) formed between the light emitting element 136, the center of the internal space 133, and the light measuring unit 139. The light measuring unit 139 can be used to preliminarily measure the back scattering of light emitted from the light emitting element 136 and passing through the internal space 133.

[0065] Device 130 is coupled to external control element 140, which includes a power source (not shown) for receiving data from light measurement units 137, 138, and 139 and processing the data to control the light output of light-emitting element 135. Light-emitting elements 135 and / or 136 can be controlled by control element 140, which can use information from light measurement units 137 and / or 138 and / or 139 to determine the state of light-emitting elements 135 and / or 136. Light measurement units 137 and / or 138 and / or 139 measure in real time the light exposure, more specifically the transmission and / or scattering, of the chemical and / or biological sample within interior space 133 and container, liner, or bag 132, as well as its optical properties, which change the light transmission of the chemical and / or biological sample itself during the course of illumination (e.g., optogenetic control, photoactivation, or photocatalysis, etc.) in real time. The control element 140 can receive and process this data and use it to effectively control the light emitting elements 135, 136, thereby controlling the illumination of the interior space 133 and the sample within the container, liner, or bag 132.

[0066] [References] 1. Anonym: Method of the Year 2010, Nature Methods VOL. 8 NO. 1, JANUARY 2011, 1-1, published online 20 December 2010, doi:10.1038 / nmeth.f.321. 2. Nicole A. Repina, Alyssa Rosenbloom, Abhirup Mukherjee, David V. Schaffer & Ravi S. Kane: AT LIGHT SPEED: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior, Annu Rev Chem Biomol Eng. 2017 June 07; 8: 13-39. doi:10.1146 / annurevchembioeng-060816-101254 3. Evan J. Olson, Lucas A. Hartsough, Brian P. Landry, Raghav Shroff & Jeffrey J. Tabor: Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals, Nature Methods VOL.11 NO.4, APRIL 2014, 449. 4. Karl P. Gerhardt, Evan J. Olson, Sebastian M. Castillo-Hair, Lucas A. Hartsough, Brian P. Landry, Felix Ekness, Rayka Yokoo, Eric J. Gomez, Prabha Ramakrishnan, Junghae Suh, David F. Savage & Jeffrey J. Tabor: An open-hardware platform for optogenetics and photobiology, Scientific Reports 6:35363, DOI: 10.1038 / srep35363. 5. Evan M. Zhao, Yanfei Zhang, Justin Mehl, Helen Park, Makoto A. Lalwani, Jared E. Toettcher, Jose L. Avalos: Optogenetic regulation of engineered cellular metabolism for microbial chemical production, Nature 555, March 2018, 683-687, DIO 10.1038 / nature26141 6. Harrison Steel, Robert Habgood, Ciaran Kelly, Antonis Papachristodoulou, Chi.Bio: An open-source automated experimental platform for biological science research, doi: https: / / doi.org / 10.1101 / 796516 7. Brandon G. Wong, Christopher P. Mancuso, Szilvia Kiriakov, Caleb J. Bashor, Ahmad S. Khalil, Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER, Nat Biotechnol. 2018 August ; 36(7): 614-623. doi:10.1038 / nbt.415

Claims

1. designed to hold at least one chemical and / or biological sample (13, 28, 45, 88, 110) or having at least one interior space (3, 16, 31, 101, 133) or having at least one container (20, 39, 72, 109, 132) designed to hold at least one chemical and / or biological sample (13, 28, 45, 88, 110); and at least one illumination means (10, 24, 44, 77, 124, 135, 136) for illuminating said chemical and / or biological sample (13, 28, 45, 88, 110) in said internal space (3, 16, 31, 61, 101, 133), which is designed to 10. The device further comprises or is equipped with at least one light measuring unit (12, 26, 47, 79, 111, 112, 137, 138, 139) designed to measure the intensity of light that has passed through and / or been scattered by the chemical and / or biological sample (13, 28, 45, 88, 110) in the interior space (3, 16, 31, 61, 101, 133).

2. the light metering unit (12, 26, 47, 79, 111, 112, 137, 138, 139) has at least one light receiving surface and is designed to measure the illuminance [lx] and / or irradiance [W / m2] of the light receiving surface; 2. The device of claim 1 .

3. 3. The device according to claim 1 or 2, characterized in that the device (1, 15, 30, 60, 100, 130) and / or the light metering unit (12, 26, 47, 79, 111, 112, 137, 138, 139) comprises at least one light filter element.

4. 4. A device according to claim 1, 2 or 3, characterized in that two or more lighting means (10, 24, 44, 77, 124, 135, 136) are provided.

5. 5. Apparatus according to any one of claims 1 to 4, characterized in that the optical metering unit (12, 26, 79) is part of an optical detection assembly (11, 27, 78) comprising at least two optical metering units (12, 26, 79).

6. 6. The device according to any one of claims 1 to 5, wherein the device (1) or the container (20, 72) has two or more cavities (2, 21, 74) designed to hold the at least one chemical and / or biological sample (13, 28, 88).

7. 6. Apparatus according to claims 4 and 5, characterized in that at least one said light measuring unit (12, 26, 79) and at least one said illumination means (10, 24, 77) are arranged in an aligned arrangement.

8. 8. The device according to claim 7, characterized in that at least one concealing element (86) is arranged between the aligned light measuring units (12, 26, 79) and the lighting means (10, 24, 77), the concealing element (86) having at least one opening (87).

9. Device according to any one of the preceding claims, characterized in that the optical metering unit (47, 111, 112, 137, 138, 139) comprises or is coupled to at least one control element (42, 122, 140).

10. 10. The device according to any one of claims 1 to 9, wherein the optical metering unit (12, 26, 47, 79, 111, 112, 137, 138, 139) comprises or is connected to at least one feedback control system and / or at least one analogue control device.

11. 1. A method for controlling exposure of at least one chemical and / or biological sample to light, wherein said sample is placed in an interior space of an illumination device and is illuminated by at least one illumination means emitting light having at least one biologically and / or chemically active wavelength, and the intensity of light transmitted through or scattered by said chemical and / or biological sample in the interior space is measured by at least one light measurement unit measuring said light intensity at said biologically and / or chemically active wavelength. A method characterized by:

12. The step of measuring the light intensity may include measuring the illuminance [lx] and / or irradiance [W / m ２ 12. The method of claim 11, comprising measuring:

13. 13. The method of claim 11 or 12, wherein the light intensity is measured over time by at least one optical recording device.

14. 14. The method of claim 13, wherein at least one illumination intensity profile and / or spectral characteristic is recorded in real time by the optical recording device.

15. A method for calibrating an optogenetic lighting device having at least one lighting means, comprising determining at least one measured value of at least one functional parameter of said lighting means, comparing said measured value with at least one measured value of said same functional parameter of at least one other lighting means, with a previously recorded value of said same lighting means, or with at least one preset and / or standard value, and determining and documenting a difference value resulting from said comparison. A method characterized by:

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