Modular sensor devices and systems for in vitro aerosol exposure

Abstract

A sensor device for an aerosol exposure system for in vitro exposure of cell cultures to a test atmosphere is described. The sensor device comprises a measurement compartment configured to receive a receptor element of an electrochemical sensor for detecting one or more components of the test atmosphere. The sensor device further comprises a receptor support disposed at an end of the measurement compartment and configured to support the receptor element of the electrochemical sensor. The sensor device further comprises a transducer element operably coupleable to the receptor element and configured to provide an electronically processable signal indicative of one or more components in the test atmosphere.

Description

[Technical field]

[0001] The present disclosure relates generally to sensor devices and systems for in vitro exposure systems, specifically in vitro aerosol exposure systems. Specifically, the present disclosure relates to sensor devices for aerosol exposure systems that expose cell cultures or surrogates thereof to a test atmosphere in vitro. Additionally, the present disclosure relates to aerosol exposure systems that include one or more of such sensor devices, the use of such sensor devices or exposure systems, and methods for determining the in vitro exposure of surrogates of cell cultures. [Background technology]

[0002] In the development and safety evaluation of products, such as consumer products that contain one or more inhalable substances that may be intentionally inhaled, such as aerosol generators, vaporizers, e-cigarettes, or inhalants, or consumer products that contain one or more inhalable substances that may be unintentionally inhaled, such as air fresheners or deodorant sprays, as well as inhaled environmental and occupational substances, such as internal combustion engine exhaust, spray paint, or kitchen smoke, in vitro methods using in vitro exposure systems are increasingly employed. Typically, these methods rely on exposing specific cells, such as cell cultures of human respiratory epithelial cells, to the substance under investigation. The actual exposure is usually followed by subsequent biological or biochemical analyses, such as cell integrity, transcriptional activity, ciliary motility, oxidative stress, formation of DNA adducts, to evaluate the safety or risk of the substance or ingredient under investigation.

[0003] The substance under investigation may refer herein to a test atmosphere that includes one or more components. The test atmosphere or substance under investigation may be or include a gas, a gas mixture, or a suspension of a liquid, or solid particles in a gas matrix, commonly referred to as an aerosol or aerosol particles. Any gaseous or solid component of the test atmosphere may be referred to herein as a component or constituent of the test atmosphere.

[0004] Typically, in vitro exposure to the test atmosphere is performed at an air-liquid interface ("ALI"), i.e., a configuration in which the cell culture forms a barrier between a liquid or gelatinous compartment, where nutrients and water are provided, and the air space, where the test atmosphere is provided. Another method is the immersion mode exposure, where a part of the test atmosphere is dissolved in a liquid or gelatinous matrix, for example, with which the cell culture is covered for exposure. This method may not be well suited for testing gases or aerosols, since the process of trapping such components of the test atmosphere in a liquid or gelatinous matrix may interfere with their physicochemical properties and thus their biological activity. Also, the conditions under which the interaction occurs between the submerged cell culture and the test atmosphere may not be physiologically representative of a typical environment for cells, such as the respiratory system, which may further affect the results obtained in the submerged exposure experiment or application.

[0005] On the other hand, ALI exposures, experiments, or applications are typically carried out in an aerosol exposure system that allows the cell culture to be contacted with the test atmosphere under controlled conditions. The aerosol exposure system typically comprises an exposure chamber into which the cell culture can be placed and into which the test atmosphere can be flowed in a controlled manner, e.g., with respect to flow rate and / or composition of the test atmosphere.

[0006] In vitro exposure at the ALI is often performed using so-called transwell cell culture inserts, which may be modified in geometry but generally feature a cylindrical or slightly conical beaker, usually made of polystyrene. The bottom of the beaker is usually composed of a porous membrane, e.g. a PET membrane. These are available in a variety of standardized size formats that accommodate 24, 12, and 6-well cell culture plates. For cell culture, the inserts can be placed in individual wells of a cell culture plate of the adapted format, containing the appropriate cell culture medium. A cell suspension can be added to each insert, and the cells will settle, grow, and form a continuous epithelial layer over time. In ALI applications, the medium can be removed from the insert, e.g., once a continuous epithelial layer is obtained. After switching from submerged culture to ALI culture, the cells are usually in contact with the surrounding air on the apical side or in the beaker, and on the basal side with the cell culture plate, the pores of the porous membrane of the insert, and the cell culture medium. Usually, the complete insert is moved into the exposure chamber of the exposure system for exposure to the test atmosphere.

[0007] In vitro exposure experiments or applications usually aim to quantify the dose associated with a test atmosphere or one or more components thereof. This can include, for example, determining measurements that correlate with the dose. As used herein, the dose associated with one or more components can refer to one or both of an administered dose and a delivered dose. Here, an administered dose may refer to the mass of one or more components of the test atmosphere provided to an exposure chamber, or the mass of one or more cell cultures contained therein. On the other hand, a delivered dose may refer to the mass of one or more components of the test atmosphere that deposits or diffuses into a test system, such as a biological test system or a sensor device described herein, during exposure.

[0008] The administered dose can typically be controlled during the exposure experiment, for example by controlling the volumetric flow rate of the test atmosphere through the exposure chamber and the exposure time, and can be calculated based on one or more of these parameters, and based on the composition of the test atmosphere, which should preferably be known.

[0009] The delivered dose may be only a portion of the administered dose and may result from or be attributed to mass transfer from the administered dose onto and / or into the cell culture. The rate of this mass transfer may be complex and may be a function of various parameters, e.g., particle size, flow rate, molecular weight in the case of aerosols, and the volatility of the test atmosphere components, as well as their potential solubility in the liquid film or layer of the cell culture. Thus, the mass transfer rate may vary for different test atmospheres and different components of a particular test atmosphere, and may depend on the experimental design, the cell culture itself, and the functional principle and design of the exposure system used. As a result, it is often not possible to infer the delivered dose from the administered dose, and it may be difficult to calculate or determine the delivered dose or other reliable measurements that correlate with it with sufficient accuracy and precision.

[0010] The biological or biochemical response to exposure, typically assessed in an in vitro exposure application or experiment, is usually primarily attributable to the delivered dose, since only components of the test atmosphere that contribute to the delivered dose may chemically and / or physically interact with the cell culture. Therefore, to accurately assess the biological and / or biochemical response of cells in an aerosol exposure application or experiment, it may be preferable to accurately determine the delivered dose and / or their associated measurements.

[0011] Measuring the delivered dose during in vitro exposure to an inhalable test substance or test atmosphere is generally performed by monitoring the deposition of the test atmosphere throughout the exposure, also referred to as online monitoring. Alternatively, in so-called post-mortem quantification, the mass of the deposited material and / or one or more components deposited on the exposed liquid or gelatinous substrate or on the exposed support structure can be determined after the actual exposure to the test atmosphere.

[0012] Online monitoring typically relies on a quartz crystal microbalance ("QCM"), which can be placed in one or several of the exposure chambers or wells of a multi-well plate in place of the cell culture. QCMs are low-cost, easy to operate, and can measure, for example, 1 cm 2Although highly sensitive down to nanograms per sieve, it can be difficult to quantitatively measure the test atmosphere delivery to the cell culture. For example, the QCM may only report the overall mass deposition, which may be a limiting factor in certain applications, e.g., when a specific component of the test atmosphere needs to be determined or measured. If all components of the test atmosphere, their mass fractions in the test atmosphere, and deposition rates are known, it is possible to theoretically estimate or calculate the mass deposition of the components of interest from the total mass deposition reported by the QCM. In practice, however, test atmospheres are generally not revealed in such detail. Very complex mixtures may consist of thousands of components, as is the case for example with combustion products. Many of them are unknown, and their contribution to the total mass of the test atmosphere, and even the rate at which they deposit on the QCM, may differ by orders of magnitude. In such cases, it may be nearly impossible to derive the exact mass deposition of individual components from the overall mass deposition reported by the QCM. Furthermore, the physical principle of mass detection by QCM relies on vibrational coupling between the liquid crystal and the deposited mass. This coupling depends on the viscoelastic properties of the deposited material and is quantitative only for solid materials. However, within the liquid layer, the vibrations typically dampen as the distance from the QCM surface increases. As the thickness of the deposition layer increases, the sensitivity decreases to detect additional deposited mass, resulting in an underestimation of mass deposition. Furthermore, the surface properties of the QCM may not be physically or chemically representative of the cell culture surface. For example, highly volatile test atmosphere components may diffuse efficiently into the cell culture, but if they diffuse onto the surface of the QCM, they may re-evaporate and go undetected as deposited mass. Finally, integration of QCMs into existing aerosol exposure systems can be difficult.

[0013] Compared to online monitoring, post-hoc determination of the delivered dose or measurements correlating therewith can provide a high level of selectivity and sensitivity. Post-hoc determination may include, for example, chromatography, optical spectroscopy, or mass spectrometry combined with microscopy, which may be used after exposing the cell culture or a suitable surrogate thereof in the test atmosphere to accurately determine the actual delivered dose. If the test atmosphere component of interest is a solid particle or a component of a solid particle, microscopy may be used to determine the dose. Depending on the particle size, optical or electron microscopy may be applied to determine the deposited dose, for example, based on the number of particles measured per area, as well as the particle size distribution, particle morphology and / or estimates on the particle surface area. Such types of post-hoc measurements and analyses can provide high selectivity and sensitivity, but can be time-consuming and dependent on the availability of expensive equipment, for example, electron microscopes or mass spectrometers, as well as highly specialized staff to operate these instruments.

[0014] It may therefore be desirable to introduce improved sensor devices for aerosol exposure systems for in vitro exposure of cell cultures to test atmospheres, and / or for in vitro exposure of surrogates of such cell cultures.

[0015] This is achieved by the subject matter of the independent claims. Optional features are provided by the dependent claims and the following description. Summary of the Invention

[0016] Aspects of the present disclosure relate to sensor devices for in vitro aerosol exposure systems, aerosol exposure systems having one or more sensor devices, uses of such sensor devices and / or aerosol exposure systems, and methods for determining in vitro exposure of a surrogate of a cell culture to a test atmosphere. Any disclosure provided herein above and below with reference to one aspect of the present disclosure applies equally to the other aspects of the present disclosure.

[0017] According to one aspect of the disclosure, a sensor device for an aerosol exposure system for in vitro exposure of a cell culture and / or a surrogate of a cell culture to a test atmosphere is provided. Here, surrogate may refer to a structure or configuration that mimics, replicates, and / or resembles a cell culture or a surface thereof. The sensor device comprises a measurement compartment configured to receive a receptor element of an electrochemical sensor for detecting one or more components of the test atmosphere. The sensor device further comprises a receptor support disposed at an end of the measurement compartment and configured to support, carry, and / or hold the receptor element of the electrochemical sensor. The sensor device further comprises a transducer element operably coupleable to the receptor element and configured to generate an electronically processable signal indicative of one or more components in the test atmosphere.

[0018] A sensor device according to the present disclosure may refer to or denote a structure carrying one or more transducer elements that can be coupled to one or more receptor elements of one or more electrochemical sensors. Note that any reference above and below to a single transducer element, receptor element, and / or electrochemical sensor includes multiple transducer elements, receptor elements, and / or electrochemical sensors.

[0019] A sensor device according to the present disclosure can be inserted, for example, into an aerosol exposure system and / or an exposure chamber of an exposure system, and can determine and / or measure, for example, the exposure of the sensor device to one or more components of a test atmosphere. If desired, the sensor device can be configured to quantify the exposure of the sensor device to one or more components of the test atmosphere, for example, based on determining a dose associated with, or a measurement correlated with, the one or more components of the test atmosphere.

[0020] The sensor device of the present disclosure may in particular make it possible to provide a low-cost, low-complexity and universally applicable sensor device, tool or system for in vitro testing, determination and / or quantification of one or more components of a test atmosphere, such as one or more inhalable substances, particles, molecules or other components of a test atmosphere. Thus, the sensor device according to the present disclosure may in particular address, or at least mitigate or overcome, one or more of the shortcomings of conventional devices and systems used to measure or quantify exposure to a test atmosphere or its components, as explained above.

[0021] For example, the sensor device described herein can be applied or utilized to quantify exposure, particularly in aerosol exposure applications, for example, to determine an in vitro dose associated with the test atmosphere and / or one or more components thereof under investigation. This can include determining the administered dose, the delivered dose, and / or one or more measurements correlating with one or more of the aforementioned doses. However, it is emphasized that the utilization or application of the sensor device of the present disclosure is not limited to the determination of the dose or measurements associated therewith. In other words, the sensor device of the present disclosure is not limited to the actual determination of the dose, dose value, or measurements correlating therewith, but can be usefully used to generally analyze or evaluate potential effects resulting from or associated with the exposure of a cell culture or sensor device to a test atmosphere in an aerosol exposure system. However, without being limited thereto, the sensor device according to the present disclosure can enable simple, affordable, broadly applicable, sensitive, and / or selective measurement and / or determination of the dose administered and / or delivered, particularly in in vitro exposure, based on or using one or more receptor elements of one or more electrochemical sensors.

[0022] In the context of the present disclosure, a test atmosphere may generally refer to a test substance or medium that includes one or more gaseous, solid, and / or liquid components that can be detected, sensed, analyzed, recognized, and / or investigated by a sensor device. The test atmosphere may be or include a gas, a mixture of gases, or a suspension of particles, or an aerosol in liquid and / or solid form in a gas matrix. Any gaseous, fluid, liquid, and / or solid components of the test atmosphere, such as gas molecules, aerosols, solid particles, or liquid particles, may be referred to herein as components or constituents of the test atmosphere and can be detected using the sensor device of the present disclosure. It is noted that the test atmosphere may include any number of components of one or more types that can be sensed or detected by the sensor device of the present disclosure.

[0023] As used herein, a receptor element may generally refer to the sensing element of an electrochemical sensor, which may be configured to physically and / or chemically interact with one or more components of the test atmosphere to be sensed or interrogated. For example, the receptor element may include biologically derived materials and / or biomimetic components configured to bind, recognize, and / or otherwise interact with one or more components of the test atmosphere. In non-limiting examples, the receptor element may include at least one of a molecularly imprinted polymer, an antibody, a receptor protein, and an enzyme configured to interact with one or more components in the test atmosphere.

[0024] The sensor device of the present disclosure can be advantageously used in conjunction with one or more receptor elements of one or more types of one or more electrochemical sensors. For example, the one or more receptor elements may be at least partially inserted into the measurement compartment of the sensor device. Alternatively or additionally, the one or more receptor elements of the one or more electrochemical sensors may be pre-mounted within the sensor device. Thus, as further described below, the sensor device of the present disclosure may include one or more receptor elements and / or may be configured to receive one or more receptor elements of one or more electrochemical sensors.

[0025] At least one transducer element of the sensor device can be functionally coupled to at least one receptor element. For example, the transducer element and the receptor element can be physically, chemically, and / or mechanically coupled such that the receptor element or a component thereof interacts with one or more of the components of the test atmosphere to provide a signal that can be detected by the transducer element and / or converted into an electronically processable signal by the transducer element. Thus, the transducer element of the sensor device of the present disclosure can be configured to detect an interaction between the receptor element and one or more components in the test atmosphere and convert the detected interaction into an electronically processable signal. Such detection of the interaction may include detection of the occurrence of the interaction per unit time, as appropriate. Thus, the electronically processable signal can be indicative of the occurrence or rate of occurrence of an interaction between one or more receptor elements and one or more components.

[0026] In one example, the interaction of the receptor element with one or more components of the test atmosphere may induce a configurational change, a structural change, a compositional change, a positional change, a change in chemical properties, a change in physical properties, and / or a change in another property or characteristic of the receptor element, which may be detectable by the transducer element. In a non-limiting example, the interaction between the receptor element and one or more components may induce a modification and / or a fluctuation in an electric field in the vicinity of the receptor element, which can be sensed and / or used by the transducer element to generate an electronically processable signal. Depending on the type of electrochemical sensor and / or receptor element used, other detection principles, e.g., optical, piezoelectric, chemical, and / or chemiluminescence-based signals induced by the interaction of the receptor element and one or more components, may also be used to detect one or more components and generate an electronically processable signal.

[0027] As used herein, an electronically processable signal may refer to an electronic signal that can be processed by a processing circuit, for example, a processing circuit of a sensor device or an aerosol exposure system. An electronically processable signal may indicate and / or include information related to the presence of one or more components in the test atmosphere, for example, detected using a transducer element based on detecting an interaction of one or more components with a receptor element. If desired, an electronically processable signal may indicate and / or include a dose associated with one or more components, a delivered dose, an administered dose, a measurement value correlating with the dose, a measurement value correlating with the administered dose, a measurement value correlating with the delivered dose, information related to the concentration of the component in the test atmosphere, and / or other information associated with or allowing exposure to be quantified or characterized.

[0028] As used herein, a measurement compartment can refer to an at least partially closed volume, vessel, or container of any shape and volume configured to at least partially surround, receive, and / or support a receptor element of an electrochemical sensor. The measurement compartment may have one or more open sides, e.g., opposite the side where the receptor support is located, for inserting or removing a receptor element into or from the measurement compartment. If desired, the measurement compartment may be closable, e.g., by a cover or lid.

[0029] A receptor support may generally refer to a support structure or support, e.g., a solid support structure, configured to carry and / or hold a receptor element. In particular, a receptor support may be configured to position, fix, and / or position a receptor element, a transducer element, and / or an electrochemical sensor within the measurement compartment, e.g., at a predetermined position or height within the measurement compartment.

[0030] In the following, various aspects and related advantages of the sensor device described herein are exemplarily summarized.The sensor device of the present disclosure can provide a structure that allows the receptor element or electrochemical sensor to be reliably, easily and reproducibly positioned in the exposure chamber of the aerosol exposure system, and allows the sensor device to be exposed to a test atmosphere containing one or more test components, such as one or more aerosols, under conditions that are the same or substantially the same as the conditions under which the cell culture is exposed to the aerosol exposure system.Therefore, the measurement value and / or electronically processable signal of the sensor device can accurately reflect and / or quantify the exposure to the cell culture.

[0031] For this purpose, the sensor device comprises a transducer element that may be functionally and / or operably coupled to one or more receptor elements of one or more electrochemical sensors, for example, based on contacting the receptor element disposed on a receptor support of the sensor device with the transducer element. The sensor device having a receptor support can be designed such that the receptor element present on the receptor support is in functional contact with the transducer element. Furthermore, the sensor device can be designed or configured such that it can be placed in an exposure chamber of an in vitro aerosol exposure system.

[0032] In one embodiment, the sensor device can be designed or configured, for example, when carrying the receptor element on the receptor support and when present in an exposure chamber of an in vitro aerosol exposure system, such that the position of the receptor element and / or its surface relative to the flow of the test atmosphere in the exposure chamber is equivalent and / or corresponds to the position of the cell culture surface during an exposure experiment in the same aerosol exposure system or chamber. Alternatively or additionally, the sensor device can be designed or configured, when carrying the receptor element and when present in an exposure chamber of an in vitro aerosol exposure system, such that the test atmosphere flow conditions in the exposure chamber are identical or substantially correspond to the test atmosphere flow conditions when the cell culture is present. For example, the sensor device can be configured or designed, when carrying the receptor and when inserted into an in vitro aerosol exposure system, such that the spatial geometry of the measurement compartment containing the receptor element substantially matches or is identical to the spatial geometry of the cavity that the cell culture faces during in vitro aerosol exposure.

[0033] In exemplary and non-limiting embodiments, the sensor device may correspond in size, shape, and / or material to a standardized cell culture insert, such as a standardized 24, 12, or 6-well transwell cell culture insert. Thus, the sensor device may be embodied as a replica or replica of a 6, 12, or 24-well cell culture insert.

[0034] Optionally, the sensor device can be configured or designed such that the transducer element and / or one or more receptor elements disposed within and / or on the sensor device can be connected to a power source, processing circuitry, processing device, or other devices or components of the sensor device or aerosol exposure system, particularly without interfering with the functional properties of the aerosol exposure system. Thus, the sensor device of the present disclosure may be compatible with existing in vitro aerosol exposure systems currently in use. The sensor device described herein is easy to handle and can be reproducibly placed in the exposure chamber of an aerosol exposure system, and can reproduce the flow pattern of the aerosol on the exposed cell culture, as well as the adsorption and electrostatic properties of a standard transwell insert. Optionally, the receptor element may provide a surface that is physically and / or chemically similar to the surface of the cell culture, such that the aerosol deposition rate on the receptor element can be very similar to the aerosol deposition rate on the exposed cell culture. This can allow for accurate determination of the dose delivered or administered in the aerosol exposure.

[0035] The sensor device of the present disclosure, as described above, can provide various advantages when compared to conventional systems utilizing QCMs for the detection of components of a test atmosphere and the quantification of exposure of cell cultures to the test atmosphere. Specifically, the use of an electrochemical sensor and a corresponding receptor element allows for a much broader spectrum of potential compounds or components of interest that can be detected and provides high selectivity, especially when a molecularly imprinted polymer or antibody is used as the receptor element. Furthermore, the electrochemical sensor can be made in a very small size, with a thickness well below one millimeter. Thus, the incorporation of the electrochemical sensor or the corresponding receptor element into the exposure chamber can realize any in vitro aerosol exposure system without the need to redesign either the system or the sensor device. Thus, the sensor device according to the present disclosure can be manufactured in large quantities and at low cost, while providing immediate readout or readout within minutes, and does not require typically expensive equipment, which makes it very time- and cost-efficient. Furthermore, the sensor device of the present disclosure is simple to operate and may not require highly qualified personnel, for example, compared to post-mortem analysis using highly sophisticated measurement equipment, such as electron microscopes.

[0036] In one embodiment, the measurement compartment of the sensor device can define an interior space of the sensor device, specifically a cylindrical interior space, configured to at least partially surround the receptor element of the electrochemical sensor along its periphery. Thus, the measurement compartment can form an interior space configured to at least partially, specifically completely contain and / or surround the receptor element along its periphery. If necessary, at least a part of the transducer element and / or at least a part of the receptor support can also be included or located within the measurement compartment. Such a configuration of the measurement compartment can allow the sensor device to closely mimic the configuration of cell cultures in standardized containers for aerosol exposure experiments, thereby allowing exposure to be accurately determined and, if necessary, quantified.

[0037] In one embodiment, the receptor support may define a bottom wall of the interior space of the sensor device. In other words, the receptor support may be arranged at an end or side of the measurement compartment, which end or side constitutes the bottom wall of the measurement compartment. For example, the measurement compartment may include an elongated body, e.g. a cylindrical body, and the receptor support may be arranged at a bottom end of the body of the measurement compartment.

[0038] Optionally, a top end of the measurement compartment opposite the bottom end may be open, allowing for insertion or removal of a receptor element or other component therein. Further, if desired, the top end may be closed by a lid or cover to protect the interior of the measurement compartment, e.g., to house the sensor device. It should be noted that directions such as "up" and "down" are intended to indicate different portions or ends of the measurement compartment, specifically when the sensor device is placed in an upright position relative to the Earth's gravitational field as intended for use.

[0039] According to one embodiment, the measurement compartment and the receptor support are coupled to each other to form a cavity of the sensor device, the cavity being configured to hold a substrate that mimics the surface of a cell culture, e.g., a cell culture medium, in particular a liquid and / or gelatinous cell culture medium, or another liquid, gelatinous, polymeric and / or porous material that mimics the surface of a cell culture. In other words, the receptor support and the measurement compartment form a container or cavity that defines an interior space of the measurement compartment, which can be configured to contain a substrate, e.g., a liquid or gelatinous substrate, that mimics or resembles the surface of a cell culture or its cell culture medium. Thus, the cavity formed by the measurement compartment and the receptor support may provide a substantially liquid-tight or gas-tight seal between the interior space of the cavity and the surroundings of the sensor device. In such a configuration, the surface of a real cell culture can be substantially similar, mimicked and / or replicated by the measurement compartment, the receptor support and the substrate, such that the measurements and / or electronically processable signals of the sensor device allow the exposure of the cell culture to be accurately determined and, if necessary, quantified.

[0040] In one embodiment, the receptor support and the measurement compartment may be integrally formed. In other words, the receptor support and the measurement compartment may be formed as a single piece, for example from the same material. Such a design may improve the overall robustness of the sensor device. Also, the manufacturing process may be simplified and manufacturing costs may be reduced.

[0041] In another embodiment, the receptor support may be fixedly attached to the end of the measurement section, for example, the receptor support may be glued, welded, soldered, or otherwise fixedly attached to the end of the measurement section, for example using a mechanical connection, such as a clamp, bolt, or screw connection.

[0042] In an exemplary embodiment, the measurement compartment and / or the sensor device are sized, shaped and formed to correspond to the interior space of the exposure chamber and / or the well of the culture plate, specifically a 6, 12 or 24 well cell culture plate, such that at least a portion of the measurement chamber is positionable within the exposure chamber and / or within the well of the cell culture plate. As explained above, aerosol exposure experiments are typically performed using 6, 12 or 24 well cell culture plates, where some or a subset of the wells contain the cell cultures and some or a subset of the wells contain the sensors or are used to determine the exposure. Forming the measurement compartment to approximately match the interior space of a multi-well cell culture plate ensures that the sensor device is at least partially inserted within the well of the cell culture plate, such that the measurement compartment and other components disposed therein, such as the receptor support, receptor element and / or gelatinous or liquid substrate, can accurately mimic the cell cultures disposed within the other wells of the cell culture plate, thereby ensuring accurate determination or quantification of the exposure of the cell cultures.

[0043] In one embodiment, the measurement compartment and / or the sensor device may be sized, shaped and formed to correspond to the interior space of the exposure chamber and / or the well of the culture plate, in particular a 6, 12 or 24 well cell culture plate, such that the receptor support and / or the receptor element of the electrochemical sensor can be placed at a predetermined position in the exposure chamber and / or in the well of the cell culture plate. A predetermined position in the exposure chamber and / or in the well of the cell culture plate may refer to a position where the outer surface of the sensor device in the measurement chamber, e.g. the surface of a gelatinous or liquid substrate covering the receptor element, is approximately coincident with or identical to the surface of the cell culture, the overlay of the cell culture or the cell culture medium covering the cell culture. Positioning the receptor support and therefore the receptor element in this way may ensure that the sensor device is exposed to the test atmosphere in a substantially identical manner to a cell culture placed in another well.

[0044] According to one embodiment, the receptor support may be arranged and / or configured to position the receptor element relative to the transducer element such that functional contact can be established between the transducer element and the receptor element of the electrochemical sensor. As used herein, functional contact refers to or includes the relative positioning of the transducer element and the receptor element, allowing for sensing of an interaction between the receptor element and one or more components of the test atmosphere. For example, the receptor support may be configured to position the receptor element near, adjacent, or in direct contact with the transducer element such that a signal generated by the receptor element upon interaction with one or more components of the test atmosphere can be sensed or detected by the transducer element and converted into an electronically processable signal. For example, interaction of the receptor element with one or more components may result in a chemical, electrical, electrostatic, or detectable signal, and the receptor support may be configured to position the receptor element sufficiently close to the transducer element to allow such a signal to be detected by the transducer element.

[0045] In one embodiment, at least a portion of the transducer element may be integrated and / or embedded in the receptor support. Such a configuration may improve the mechanical robustness of the sensor device. It may also ensure accurate relative positioning of the transducer element, receptor support, and, if necessary, receptor element, thereby improving the accuracy of exposure detection.

[0046] Alternatively or additionally, at least some of the transducer elements may be attached to a side of the receptor support facing the interior space defined by the measurement compartment. For example, at least some of the transducer elements may be arranged on a bottom side or wall of the measurement compartment. If desired, at least some of the transducer elements may be arranged within the measurement compartment. For example, at least some of the transducer elements may be arranged on an inner surface of the measurement compartment. This may allow for improved sensitivity of the sensor device, since the transducer elements collect signals generated near their position within the measurement compartment.

[0047] In an exemplary embodiment, the transducer element may comprise an electrode array arranged on the side of the receptor support facing the measurement compartment. The electrode array may then comprise a working electrode, a counter electrode and a reference electrode. However, the array may also comprise more than three electrodes. For example, the electrode array may be arranged on the inner surface of the bottom wall or side of the measurement compartment, with the inner surface facing the interior space of the measurement compartment. The electrode array may be in direct contact with the interior space of the measurement compartment or may be covered by a layer of material for protection.

[0048] In general, the transducer elements and / or electrode arrays may be configured to detect and / or sense the occurrence of an interaction or interaction between the receptor elements and one or more components of the test atmosphere based on detection of a change, modification, or variation in the electric field surrounding the electrode array. As an example, the electrode array may be powered to generate an electric field around a portion of the transducer elements. An interaction between the receptor elements and the components may, for example, induce a structural or other change in the receptor elements, which may locally distort the electric field around the electrode array or change the ionic composition. The modification or distortion of the electric field may then be sensed by the transducer elements, and an electronically processable signal may be generated in response. Thus, the electrical signal detected by the transducer elements in response to the interaction is the electronically processable signal. Alternatively, the electronically processable signal may be generated based on the signal detected by the transducer elements in response to the interaction, which may include, for example, amplification of the signal detected by the transducer elements.

[0049] In yet another example, the sensor device comprises at least one receptor element of an electrochemical sensor. The receptor element may thus be pre-attached to the sensor device, for example to provide a ready-to-use sensor device. If necessary, the sensor device may be activated before use, for example by providing a liquid and / or gelatinous matrix in the measurement compartment mimicking a cell culture.

[0050] As described above, the receptor element of the electrochemical sensor may be configured to physically and / or chemically interact with one or more components of the test atmosphere. For example, interaction of the receptor element with one or more components of the test atmosphere may induce a configurational change, a structural change, a compositional change, a positional change, a change in chemical properties, a change in physical properties, and / or a change in another property or characteristic of the receptor element, which may be detectable by the transducer element. Furthermore, the transducer element may be configured to detect an interaction between the receptor element and one or more components in the test atmosphere and convert the detected interaction into an electronically processable signal. This may include processing and / or amplification of the signal detected by the transducer element in response to the occurrence of an interaction between the receptor element and one or more components, as necessary.

[0051] In one embodiment, the transducer elements may be configured to transmit electronically processable signals to a signal processor. The transducer elements may be communicatively and / or operatively coupled to a signal processor (also referred to herein as a processor) to transmit electronically processable signals to the signal processor, where the coupling may be a wired or wireless coupling.

[0052] The signal processor may be part of the sensor device. Alternatively or additionally, the signal processor may be part of the aerosol exposure system. In general, the signal processor may include a processing circuit having one or more processors for data processing. The processing circuit may also include other components, such as an amplifier circuit for amplifying the signal received at the transducer element in response to the interaction between the receptor element and one or more components.

[0053] In non-limiting examples, the measurement compartment and / or receptor support may include one or more of glass, polystyrene, polyethylene terephthalate, polydimethylsiloxane, stainless steel, polyetheretherketone, Teflon, and silicon. Other materials or material compositions may also be used. Such materials may be particularly advantageous as they are non-reactive or inert and may not adversely affect or influence the actual measurement.

[0054] In yet another embodiment, the receptor element can include at least one of a molecularly imprinted polymer, an antibody, a receptor protein, and an enzyme configured to interact with one or more components in the test atmosphere. For example, the receptor element can include a layer of at least one of a molecularly imprinted polymer, an antibody, a receptor protein, and an enzyme configured to interact with one or more components in the test atmosphere. Such receptor elements can provide high selectivity and high sensitivity for detecting one or more components in the test atmosphere. Thus, aerosol exposure can be reliably and accurately determined, and optionally quantified, based on, for example, a dose, an administered dose, a measurement correlated with the dose, and / or a delivered dose determination.

[0055] Moreover, such receptor elements can be made very small in size, well below a millimeter in thickness, and thus the incorporation of an electrochemical sensor or a corresponding receptor element into an exposure chamber can be implemented in any in vitro aerosol exposure system without the need to redesign either the system or the sensor.

[0056] In yet another embodiment, the sensor device may further comprise a layer of liquid and / or gelatinous matrix at least partially covering the molecularly imprinted polymer, the antibody, the receptor protein, and / or the enzyme. If necessary, the layer of liquid and / or gelatinous matrix may provide a physical and chemical environment that may be suitable for the functioning of the receptor element and / or the transducer element. For example, if a conductive bridge between the working electrode and the counter electrode is to be established, the matrix layer may be conductive and may be adjusted with respect to its electrical properties. Alternatively or additionally, the layer of liquid and / or gelatinous matrix may provide a physical and chemical environment similar to the surface of a cell culture cultivated at the ALI. For example, the matrix layer may be adjusted with respect to solvent polarity, surface tension, and / or pH value.

[0057] If necessary, the substrate layer is considered as part of the receptor element of the sensor device and the dimensions of the sensor device must take into account the thickness of this liquid layer, so that the position of the surface of the receptor element can be matched with the position of the surface of the cell culture relative to the geometry of the exposure chamber, as is exemplarily described in detail with reference to FIG. 2.

[0058] In general, the type and number of receptor elements can be selected according to the actual application or the component or components to be investigated. Since the same or different types of receptor elements or multiple receptor elements can be selected, the sensor device described herein can constitute a modular sensor system for an in vitro aerosol exposure system. Also, at least a part of the sensor device can be reused multiple times, for example, with different receptor elements.

[0059] In an exemplary embodiment, the receptor element includes multiple molecularly imprinted polymers, antibodies, receptor proteins, and / or enzymes of different types, each type configured to interact with a different type of component in the test atmosphere. The use of different types of receptor elements to detect different types of components may enable detection of a wide range of components with high selectivity and sensitivity.

[0060] In one embodiment, the transducer element and / or the receptor support may be configured to directly contact at least a portion of the receptor element. For example, the receptor element and / or its material may be directly deposited on at least a portion of the receptor support, for example, based on pipetting the receptor material into the measurement compartment and other deposition techniques. By contacting the receptor element with the transducer element, the interaction between the receptor element and one or more components can be reliably detected with high accuracy and precision. Thus, the sensitivity of the sensor device can be improved.

[0061] In yet another exemplary embodiment, the sensor device may further comprise an interface for coupling the sensor device to a power source and / or for coupling the sensor device to a processor or signal processor, where the power source and / or processor may be part of the sensor device or may be part of the aerosol exposure system. The interface may be configured for electrically coupling the sensor device to the power source and / or for communicatively coupling the sensor device to the processor. One or both of the electronic coupling and the communicative coupling may be wired or wireless. Wireless electronic coupling may include, for example, inductive coupling and / or capacitive coupling.

[0062] In one embodiment, the interface may be configured for independent readout of signals of multiple receptor elements and / or transducer elements. Thus, the interface may be communicatively coupled to multiple transducer elements and / or receptor elements of the same or different types to separately obtain multiple measurement signals, each signal corresponding to one or a subset of the receptor / transducer elements of the multiple receptor / transducer elements. The multiple measurement signals may then form an electronically processable signal. Alternatively, each of the independent measurement signals may be an electronically processable signal. In particular, the independent readout may improve the selectivity of the sensor device. Also, the spectrum of detectable components may be broadened.

[0063] According to one embodiment, the interface may be configured for one or more of inductive, electronic, capacitive, and optical coupling. Any one or more of the aforementioned couplings may be used to couple the sensor device to a power source and / or processing device.

[0064] In yet another embodiment, the sensor device further comprises one or more leads or wires in contact with the transducer elements for electrical supply and / or for transmitting electronically processable signals to the processor. Using leads or wires for power supply and communication or for transmitting electronically processable signals may allow for a mechanically robust connection to be established.

[0065] In an exemplary embodiment, one or more leads or wires may extend from the transducer element along a wall, in particular an outer wall, of the measurement compartment towards another end of the measurement compartment. The other end of the measurement compartment may refer to a top end of the measurement compartment, which is located opposite a bottom end of the measurement compartment, where a receptor support may be located. The leads or wires may be located on a surface of the measurement compartment, for example on an outer surface of the body of the measurement compartment, which faces away from the interior space of the measurement compartment. If necessary, the leads may be covered by an insulating material for protection. Alternatively or additionally, at least a part of the leads may extend through the wall of the measurement compartment. For example, the leads may be at least partially embedded or embedded in the outer wall of the measurement compartment or its body.

[0066] In yet another embodiment, the sensor device further comprises a holder configured to accommodate at least a portion of the measurement compartment, in particular the measurement compartment may be disposed in the holder after exposure to the test atmosphere, e.g. for a post-mortem readout.

[0067] Optionally, the holder may comprise an interface configured to establish an electronic connection with the transducer element when the measurement section is accommodated within the holder. In particular, an electronic coupling between the transducer element and a power source may be established. Alternatively or additionally, a communicative coupling may be established between the transducer element and a processing device.

[0068] Furthermore, if desired, the holder may comprise, for example on its surface, one or more guides formed corresponding to one of the guides disposed on the surface of the measurement section, such that the measurement section may be inserted into the holder in a predefined orientation and the leads of the measurement section may coincide with an interface of the holder. Generally, such a configuration and design may simplify handling and operation of the sensor device.

[0069] In non-limiting examples, the transducer element may include one or more of gold, platinum, and glassy carbon. In particular, one or more electrodes of the transducer element may include one or more of the aforementioned materials, as these materials may be considered to be highly conductive but chemically non-reactive materials. Other materials may also be used, but preferably the material does not alter or affect the physical and chemical environment of the transducer element or a receptor element disposed in close proximity thereto.

[0070] According to one embodiment, the transducer elements may be configured for one or more of voltametric, amperometric, and impediometric readouts. Alternatively or additionally, electronically processable signals may be read from the transducer elements by a processing device, for example based on the voltametric, amperometric, and / or impediometric readouts.

[0071] In one embodiment, the sensor device further comprises a processing unit configured to process the electronically processable signals generated by the transducer elements into a measurement value correlating with a dose associated with one or more components of the test atmosphere, wherein the measurement value correlating with the dose may refer to a physical quantity indicative of and / or a dose associated with the one or more components and / or proportional to the dose. Thus, the processing unit can be configured to quantify the exposure based on processing the electronically processable signals and calculating the exposure or the dose associated with the one or more components.

[0072] The processing device can be configured to determine and / or calculate an administered dose indicative of the mass of one or more components of the test atmosphere delivered to an exposure chamber of the aerosol exposure system. The processing device may, as appropriate, take into account one or more parameters related to the exposure and / or the one or more components to calculate the administered dose.

[0073] Alternatively or additionally, the processing device can be configured to determine and / or calculate a delivered dose indicative of the mass of one or more components of the test atmosphere deposited on and / or transferred into the receiver element. As explained above, the delivered dose may provide reliable information regarding the response, e.g., biological or biochemical response, of the cell culture to one or more components of the test atmosphere.

[0074] Optionally, the processing device may be configured to determine a measurement that correlates with dose, e.g., correlates with administered dose and / or delivered dose, based on one or more of the particle size of one or more components, the deposition rate of one or more components, the molecular weight of one or more components, the volatility of one or more components, the solubility of one or more components, the volumetric flow rate through the exposure chamber, the exposure time, and the composition of the test atmosphere. Given one or more of the aforementioned parameters related to exposure and / or one or more components, the measurement that correlates with dose may be able to be calculated with precision and accuracy.

[0075] Further, if desired, the processing device may be configured to determine a biochemical and / or biological response of the receptor element to the one or more components. Such biochemical and / or biological response may be determined based on a determined measurement that correlates with dose, in particular based on an administered dose. Determining the biological and / or biochemical response may assess the safety of the one or more components to the respective cell culture or cells thereof, and thus potentially to humans, for example if the one or more components under investigation are inhalable substances.

[0076] In one example, the processing device may be configured for online monitoring and / or post-mortem analysis of in vitro exposure of the cell culture to the test atmosphere. For example, the processing device may read or receive one or more electronically processable signals from the transducer elements during exposure, thereby allowing for online monitoring of the exposure in real-time or near real-time. Alternatively or additionally, the processing device may read out the transducer elements after exposure, and the corresponding electronically processable signals may be indicative of any interactions between the receptor elements and one or more components that occurred during exposure.

[0077] A further aspect of the present disclosure relates to an aerosol exposure system for in vitro exposure of cell cultures to a test atmosphere. Any disclosures given above and below with reference to a sensor device apply equally to the aerosol exposure system and vice versa. The system comprises one or more sensor devices as described above and below. The system further comprises a processing device or signal processing device for processing electronically processable signals generated by the one or more sensor devices. Here, the processing device may be operatively and / or communicatively coupled to at least one sensor device.

[0078] In one example, the exposure system may comprise a 6, 12, or 24 cell culture plate, where some or a subset of the wells may contain cell cultures, and one or more wells may comprise one or more sensor devices, as described hereinabove and below. The cell culture plate may be placed in an exposure chamber of the exposure system and exposed to a test atmosphere. Because the one or more sensor devices mimic or resemble the cell cultures in terms of location, exposure geometry, physical properties, and / or chemical properties, electronically processable signals collected from the one or more sensor devices allow for accurate determination or calculation of the exposure of the cell cultures, which may include quantification of the exposure, if desired, for example, based on determining a measurement that correlates with a dose.

[0079] In one embodiment, the system may further comprise an exposure trumpet for directing a flow of the test atmosphere into the measurement compartment of the one or more sensor devices. The flow of the test atmosphere may be controlled in terms of flow rate, volumetric flow rate, and / or spatial exposure using the trumpet, thereby allowing the exposure to occur under controlled and / or reproducible conditions.

[0080] In an example embodiment, the processing unit may be configured for independent readout of multiple sensor devices of the system. For example, multiple sensor devices of the same or different types may be utilized, e.g., using different types of receptor elements. The use of multiple sensor devices that can be read out independently may enable the detection of a wide range of different constituents, particularly when using different types of sensor devices, e.g., having different types of receptor elements.

[0081] Another aspect of the present disclosure relates to the use of the sensor device described above and below and / or the aerosol exposure system described above and below for determining and / or quantifying the exposure of a cell culture to a test atmosphere, particularly for dose assessment.

[0082] According to another aspect of the present disclosure, there is provided a method for determining in vitro exposure of a surrogate of a cell culture, e.g., a liquid and / or gelatinous cell culture medium, to a test atmosphere containing one or more components of interest. The method includes: - providing a sensor device as described above and below; - placing a receptor element of an electrochemical sensor in a measurement compartment of a sensor device; - exposing the sensor device and the receptor element to a test atmosphere; - generating, using a transducer element of the sensor device, an electronically processable signal indicative of one or more components of the test atmosphere.

[0083] The method can optionally include determining a dose and / or a dose-correlated measurement associated with one or more components of the test atmosphere based on processing the generated signal with a processor of the sensor device or a processor of the aerosol exposure system. EXAMPLES

[0084] The following provides a non-exhaustive list of non-limiting examples, any one or more of the features of which may be combined with any one or more features of another example, embodiment, or aspect described herein.

[0085] Example 1: 1. A sensor device for an aerosol exposure system for in vitro exposure of a cell culture to a test atmosphere, the sensor device comprising: a measurement compartment configured to receive a receptor element of an electrochemical sensor for detecting one or more components of the test atmosphere; a receptor support disposed at an end of the measurement compartment and configured to support a receptor element of the electrochemical sensor; a transducer element operably couplable to the receptor element and configured to provide an electronically processable signal indicative of one or more components in the test atmosphere. Example 2: The sensor device of Example 1, wherein the measurement compartment defines an interior space of the sensor device, in particular a cylindrical interior space, configured to circumferentially at least partially surround the receptor element of the electrochemical sensor. Example 3: The sensor device of example 2, wherein the receptor support defines a bottom wall of an interior space of the sensor device. Example 4: A sensor device described in any one of Examples 1 to 3, wherein the measurement compartment and the receptor support together form a cavity of the sensor device, and the cavity is configured to hold a substrate that mimics the surface of a cell culture, such as a cell culture medium, in particular a liquid and / or gelatinous cell culture medium, or another liquid, gelatinous, polymeric and / or porous material that mimics the surface of a cell culture. Example 5: A sensor device according to any one of Examples 1 to 4, wherein the receptor support and the measurement compartment are integrally formed. Example 6: A sensor device according to any one of the preceding embodiments, wherein the receptor support is fixedly attached to an end of the measurement compartment. Example 7: A sensor device described in any one of Examples 1 to 6, wherein the measurement compartment and / or sensor device are sized, shaped and formed to correspond to the interior space of the exposure chamber and / or well of a culture plate, specifically a 6, 12 or 24 well cell culture plate, such that at least a portion of the measurement chamber is positionable within the exposure chamber and / or well of the cell culture plate. Example 8: A sensor device described in any one of Examples 1 to 7, wherein the measurement compartment and / or sensor device are sized, shaped and formed to correspond to the interior space of the exposure chamber and / or well of a culture plate, specifically a 6, 12 or 24 well cell culture plate, such that the receptor support and / or receptor element of the electrochemical sensor can be positioned at a predetermined position within the exposure chamber and / or well of the cell culture plate. Example 9: A sensor device described in any one of Examples 1 to 8, wherein the receptor support is arranged and / or configured to position the receptor element relative to the transducer element, thereby establishing functional contact between the transducer element and the receptor element of the electrochemical sensor. Example 10: A sensor device according to any one of the preceding embodiments, wherein at least a portion of the transducer element is integrated into and / or embedded within the receptor support. Example 11: A sensor device according to any one of the preceding embodiments, wherein at least a part of the transducer element is attached to a side of the receptor support facing the interior space defined by the measurement compartment. Example 12: A sensor device according to any one of the preceding embodiments, wherein the transducer element comprises an electrode array arranged on a side of the receptor support facing the measurement compartment, the array preferably comprising a working electrode, a counter electrode and a reference electrode. Example 13: The sensor device according to any one of Examples 1 to 12, further comprising at least one receptor element of an electrochemical sensor. Example 14: The sensor device according to any one of Examples 1 to 13, wherein the receptor element of the electrochemical sensor is configured to physically and / or chemically interact with one or more components of the test atmosphere. Example 15: A sensor device described in any one of Examples 1 to 14, wherein the transducer element is configured to detect an interaction between the receptor element and one or more components in the test atmosphere and convert the detected interaction into an electronically processable signal. Example 16: The sensor device of Example 15, wherein the transducer element is configured to transmit an electronically processable signal to a signal processor. Example 17: 17. The sensor device of any one of Examples 1 to 16, wherein the measurement compartment and / or receptor support comprises one or more of glass, polystyrene, polyethylene terephthalate, polydimethylsiloxane, stainless steel, polyetheretherketone, Teflon, silicon. Example 18: A sensor device described in any one of Examples 1 to 17, wherein the receptor element comprises at least one of a molecular imprinted polymer, an antibody, a receptor protein, and an enzyme configured to interact with one or more components in the test atmosphere, and preferably the receptor element comprises a layer of at least one of a molecular imprinted polymer, an antibody, a receptor protein, and an enzyme configured to interact with one or more components in the test atmosphere. Example 19: The sensor device of Example 18, further comprising a layer of liquid and / or gelatinous matrix at least partially covering the molecularly imprinted polymer, antibody, receptor protein, and / or enzyme. Example 20: A sensor device described in any one of Examples 1 to 19, wherein the receptor element comprises a plurality of molecular imprinted polymers, antibodies, receptor proteins, and / or enzymes of various types, each type configured to interact with a different type of component in the test atmosphere. Example 21: 21. The sensor device of any one of Examples 1-20, wherein the transducer element and / or the receptor support is configured to directly contact at least a portion of the receptor element. Example 22: The sensor device of any one of Examples 1 to 21, wherein the receptor element and / or material is deposited directly onto at least a portion of the receptor support. Example 23: The sensor device of any one of Examples 1-22, wherein the one or more components in the test atmosphere include an inhalable substance. Example 24: The sensor device of any one of Examples 1 to 23, further comprising an interface for coupling the sensor device to a power source and / or a processing device. Example 25: 25. The sensor device of example 24, wherein the interface is configured for independent readout of signals of multiple receptor elements. Example 26: A sensor device described in any one of Examples 24 and 25, wherein the interface is configured for one or more of inductive coupling, electronic coupling, electrostatic coupling, and optical coupling. Example 27: A sensor device described in any one of Examples 1 to 26, further comprising one or more leads contacting the transducer element for electrical supply and / or for transmitting an electronically processable signal to a processing device. Example 28: 28. A sensor device as described in Example 27, wherein one or more lead wires extend from the transducer element along a wall, particularly an outer wall, of the measurement compartment toward another end of the measurement compartment. Example 29: The sensor device according to any one of Examples 1 to 28, further comprising a holder configured to accommodate at least a portion of the measurement compartment. Example 30: 30. The sensor device of example 29, wherein the holder comprises an interface configured to establish an electronic connection with the transducer element when the measurement compartment is accommodated within the holder. Example 31: The sensor device of any one of Examples 1-30, wherein the transducer element comprises one or more of gold, platinum, and glassy carbon. Example 32: A sensor device according to any one of Examples 1 to 31, wherein the transducer element is configured for one or more of voltammetric, amperometric, and / or impediometric readout. Example 33: A sensor device described in any one of Examples 1 to 32, further comprising a processing device configured to process an electronically processable signal generated by the transducer element into a measurement value correlating with a dose associated with one or more components of the test atmosphere. Example 34: The sensor device of Example 33, wherein the processing device is configured to determine an administered dose indicative of the mass of one or more components of the test atmosphere supplied to the exposure chamber of the aerosol exposure system. Example 35: The sensor device of Example 33 or 34, wherein the processing device is configured to determine a delivered dose indicative of the mass of one or more components of the test atmosphere deposited on and / or transferred into the receptor element. Example 36: The sensor device of any one of Examples 33 to 35, wherein the processing unit is configured to determine a measurement value that correlates to the dose based on one or more of the following: particle size of one or more components, deposition rate of one or more components, molecular weight of one or more components, volatility of one or more components, solubility of one or more components, volumetric flow rate through the exposure chamber, exposure duration, and composition of the test atmosphere. Example 37: The sensor device of any one of Examples 33-36, wherein the processing unit is configured to determine a biochemical response of the receptor element to the one or more components. Example 38: The sensor device of any one of Examples 33 to 37, wherein the processing unit is configured for online monitoring and / or post-analysis of in vitro exposure of the cell culture to the test atmosphere. Example 39: 1. An aerosol exposure system for in vitro exposure of a cell culture to a test atmosphere, the system comprising: One or more sensor devices according to any one of Examples 1 to 38; and a processing device for processing electronically processable signals generated by one or more sensor devices. Example 40: The system of Example 39, further comprising an exposure trumpet for directing a flow of the test atmosphere into the measurement compartment of the one or more sensor devices. Example 41: A system described in any one of Examples 39 and 40, wherein the processing device is configured for independent readout of multiple sensor devices of the system. Example 42: Use of a sensor device as described in any one of Examples 1 to 38 or a system as described in any one of Examples 39 to 41 for determining the exposure of a cell culture to a test atmosphere, in particular for dose assessment. Example 43: 1. A method for determining in vitro exposure of a surrogate of a cell culture (e.g., liquid and / or gelatinous cell culture medium) to a test atmosphere containing one or more components of interest, the method comprising: Providing a sensor device according to any one of Examples 1 to 38; placing a receptor element of an electrochemical sensor within a measurement compartment of a sensor device; exposing the sensor device and the receptor element to a test atmosphere; and generating, with a transducer element of the sensor device, an electronically processable signal indicative of one or more components of the test atmosphere. Example 44: The method of example 43, further comprising determining a dose associated with one or more components of the test atmosphere based on processing the signal generated with the sensor device or a processing device of the aerosol exposure system. [Brief description of the drawings]

[0086] The embodiments will now be further described with reference to the following figures:

[0087] [Figure 1] FIG. 1 shows a perspective view of a sensor device for an aerosol exposure system. [Diagram 2] FIG. 2 shows a cell culture insert compared to a sensor device for an aerosol exposure system. [Diagram 3] FIG. 3 shows the aerosol exposure system. [Figure 4] FIG. 4 shows a flow chart illustrating a method for determining the in vitro exposure of a cell culture surrogate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0088] The figures are only schematic and are not to true scale. As a rule, identical or similar parts, elements and / or steps are given identical or similar reference signs in the figures.

[0089] FIG. 1 shows a perspective view of a sensor device 100 for an aerosol exposure system 500 (see FIG. 3) according to one embodiment.

[0090] The sensor device 102 comprises a measurement compartment 102 for at least partially receiving, containing and / or surrounding a receptor element (209, see FIG. 2) of a biochemical sensor that can be placed within the measurement compartment 102 to determine exposure. The measurement compartment 102 comprises an open or top end 105, through which the receptor element 209 and optionally other components can be inserted or removed from the measurement compartment 102. The measurement compartment 102 further comprises a generally cylindrical body 101 forming or defining an interior space 107 within which the receptor element 209 can be placed to measure exposure to a test atmosphere.

[0091] Located at a bottom end 103 opposite the top end 105 relative to the longitudinal axis of the measurement compartment 102 or sensor device 100 is a receptor support 104 configured to support, hold, and / or position a receptor element 209 within an interior space 107 of the measurement compartment 102. The receptor support 104 may define a bottom wall 109 or surface 109 of the measurement compartment 102.

[0092] 1, the receptor support 104 is integrally formed with the body 101 of the measurement section 102. Alternatively, the receptor support 104 may be fixedly attached to the body 101 by a suitable connection, for example a clamp connection, a screw connection, an adhesive bond, welding or soldering.

[0093] The sensor device 100 further comprises a transducer element 106. In the embodiment of Fig. 1, the transducer element 106 comprises an array 110 of three electrodes 110a, 110b, 110c, specifically a counter electrode 110b, a reference electrode 110a, and a working electrode 110c. In the embodiment shown in Fig. 1, the electrodes may be planar or flat electrodes, and the counter electrode 110b may be located at the center of the array 110, while the working electrode 110c and the reference electrode 110a may be located around a portion of the circumference of the counter electrode 110b to provide a highly sensitive electrode array 110.

[0094] The transducer elements 106 of the embodiment of FIG. 1 are disposed on a bottom wall 109 of the measurement compartment 102 defined or formed by the receptor support 104. For example, the transducer elements 106 may be disposed on an inner surface of the bottom wall 109 facing the interior space 107 of the measurement compartment 102. The transducer elements 106 and / or the array 110 of electrodes 110a-c may be printed or glued onto the inner surface of the bottom wall 109, for example. If necessary, the electrode array 110 may be covered by a layer of protective material. The transducer elements 106 and / or the electrode array 110 may comprise one or more of gold, platinum, and glassy carbon.

[0095] The sensor device 102 further comprises a plurality of leads 112, with each of the electrodes 110a-c coupled to at least one of the leads 112. The leads 112 extend from the electrode array 110 and / or the bottom wall 109 towards the top end 105 or a rim at the top end 105, where the leads 112 are configured to electrically couple the sensor device 100 to a power source 118 and / or communicatively couple the sensor device 100 or the transducer element 106 to a processing device 120 configured to process one or more electronically processable signals generated by the transducer element 106 in response to an interaction of the receptor element 209 with one or more components in the test atmosphere, as described in more detail above and below. The power source 118 and / or the processing device 120 may be part of the sensor device 100 or may be part of an aerosol exposure system 500 to which the sensor device 100 can be connected.

[0096] To actually couple the sensor device 100 to a power source 118 and a processing unit 120 , the leads 112 of the sensor device 100 couple to or form an interface 114 of the sensor device 100 that is located at the top end 105 of the sensor device 100 .

[0097] In the following, various aspects of the sensor device 100 are described and summarized. The sensor device 100 and / or the measurement compartment 102 may refer to a solid structure whose size, shape, and materials may replicate or mimic a standardized 24-well, 12-well, or 6-well cell culture insert. The electrode array 110 may be disposed inside or on the surface of the bottom wall 109 of the measurement compartment 102, which may be referred to as a transwell replica. The array 110 comprises a working electrode 110c, a counter electrode 110b, and a reference electrode 110a. The electrode array 110 may be part of a transducer element 106 that may be coupled to a receptor element 209 of an electrochemical sensor. The receptor element 209 of the electrochemical sensor, e.g., a molecularly imprinted polymer or other receptor element, may be deposited directly on the electrodes 110a-c. The leads 112 may be present in or on the side walls of the measurement compartment 102 or its body 101. The leads 112 can lead to the measurement compartment 102 or to the top end 105 or edge of the sensor device 100. An interface 114, or means for establishing an electrical connection to a power source 118 and / or a processing unit 120, such as a potentiostat, galvanostat, and / or impedance analyzer, is provided at the top end 105 of the sensor device 100. Optionally, a receptor element 209 of an electrochemical sensor may be located within the measurement compartment 102.

[0098] The receptor elements 209 may preferably be in direct contact with the electrode array 110 and / or the transducer elements 106. Optionally, the receptor elements 209 may include a thin functional layer, such as a layer of a molecularly imprinted polymer, an immobilized antibody, an immobilized enzyme, a protein, or other material as described herein.

[0099] Further, if desired, the sensor device 100 may comprise a holder (not shown) for subsequent readout. For example, the holder may be configured to at least partially accommodate the measurement section 102 after exposure. The holder may comprise electrical connectors or interfaces, such that upon insertion of the measurement section 102, a connection may be established between the transducer elements 106, the interface 114, and / or the leads 112, and, if desired, the power supply 118, and / or the processing unit 120. The holder may be shaped to correspond to the measurement section 102, such that the measurement section 102 fits snugly within the holder. If desired, the holder may comprise one or more guides configured to engage with one or more correspondingly shaped guide elements or guides located on the measurement section 102 or on its outer surface, such that the orientation of the measurement section 102 may be aligned with the electrical connections or interfaces present, for example by default, on the holder.

[0100] The measurement section 102 can be made of any suitable material, such as glass, polystyrene, polyethylene terephthalate, and polydimethylsiloxane. Depending on the material selected, it can be manufactured by machining, additive manufacturing, or injection molding, and, if desired, at least a portion of the transducer element 106 may be embedded in the measurement section 102 or in its walls.

[0101] The electrodes 110a-c and leads 112 can be made from any suitable material compatible with electrochemical applications, such as gold, platinum, and glassy carbon, and may be attached by any practicable method, such as by gluing individual electrodes 110a-c or leads 112 or the complete electrode lead array 110, 112 on the bottom wall 109 of the measurement compartment 102, for example by screen printing.

[0102] The receptor element 209 may be deposited within the measurement zone 102, for example by a user, onto the electrodes 110a-c, allowing for modular and custom tuning of the selectivity of the sensor device 100. In such an example, the sensor device 100 may comprise the measurement zone 102, the transducer element 106, the receptor support 104, and leads 112 and / or interface 114 as required.

[0103] In another configuration, the sensor device 100 may be ready for use and the receptor element 209 may be present and in operative communication with the transducer element 106. In such a case, the analytes or components of interest of the test atmosphere to be detected by the sensor device 100 may be predefined.

[0104] The receptor element 209 can be deposited on the receptor support 104 by any suitable method, including manual deposition, for example by pipetting, optionally followed by thermal or UV curing. Other deposition techniques may include spraying, printing, spin coating, and electropolymerization.

[0105] The receptor element 209 may be, for example, a bioreceptor, such as a nucleic acid, antibody, protein or enzyme based receptor, or a molecularly imprinted polymer (MIP). The readout may be, for example, voltammetric, amperometric, or impediometric. The particular sensor parameters, such as sensitivity, selectivity, and dynamic range, may depend on the analyte or component of interest, i.e., the component of interest of the test atmosphere under investigation.

[0106] For example, one or more types of receptor elements 209 may be present simultaneously in the same measurement zone 102 if several test atmosphere components are targeted simultaneously within the zone 102. Separate electrical connections 112, 114 may be made to each receptor element 209 as well as to a single receptor element 209.

[0107] In use, one or more measurement compartments 102 may be placed in one or more exposure chambers of the aerosol exposure system 500 (see FIG. 3), and the system 500 may be closed and operated as during a normal aerosol exposure experiment. When the system 500 comprises several exposure chambers, the chambers not occupied by sensors may be used for cell culture exposure, since the presence of sensors in other chambers does not interfere with system function.

[0108] Furthermore, the sensor device may operate in two different modes of operation: the exposure system 500 allows for electrical connections to the sensor device 100 in the exposure system 500 during exposure, allowing real-time or online measurements of deposition of the test atmosphere to be performed. Alternatively, a post-mortem readout can be performed, for example if the exposure system 500 does not allow for electrical connections to be provided in the exposure chamber. After exposure is complete, the sensor device 100 or measurement section 102 including the receptor element 209 and the test atmosphere components deposited on and / or within it during exposure can be removed from the system 500 and connected to the power source 118 and the processing device 120 to measure the mass of deposition of the test atmosphere components of interest.

[0109] For this purpose the holder in which the measurement compartment 102 can be placed as required can be placed in a closed container in which the physical and chemical conditions can be controlled in order to provide optimal conditions for the readout and to avoid the occurrence of artefacts and contamination: for example a protective atmosphere can be formed or the temperature can be kept within an optimal range for the sensor.

[0110] In summary, the sensor device 100 described herein preferably comprises a physical receptor support 104, which allows the receptor element 209 to be positioned within the aerosol exposure system 500 at a location equivalent to that of a cell culture during in vitro exposure to, for example, an inhalable test substance, as well as a means or interface 114 for connecting the sensor device 100 to a processing device 120, which allows the sensor output or electronically processable signal to be converted into a result that can be read and interpreted by a human. The receptor support 104 may comprise a portion of the transducer element 104 or transducer element 106. If desired, the sensor device 100 may comprise a receptor element 209 disposed on the support 104 and / or transducer element 106, as described in more detail with reference to FIG. 2.

[0111] Figure 2 shows a standard cell culture insert 201 on the left side of the figure in comparison with a sensor device 100 for an aerosol exposure system proposed herein and shown on the right side of Figure 2. Unless otherwise stated, the sensor device 100 of Figure 2 includes the same elements, features, and functions as the sensor device 100 of Figure 1.

[0112] In the exemplary embodiment of the sensor device 100 shown in Fig. 2, a solid receptor support 104 may be placed at the bottom end 103 of the measurement compartment 102, on which a receptor element 209 of the electrochemical sensor may be deposited. The receptor support 104 may form the bottom wall 109 of the measurement compartment 102, on which in a standard transwell cell culture insert 201 a porous membrane 205 is placed. The form of the sensor device 100 may correspond to the 6, 12 or 24 well form of a standard transwell cell culture insert 201.

[0113] Depending on the surface properties and function principle of the receptor element 209, a thin layer 210 of a suitable liquid and / or gelatinous substrate 211 may be deposited on top of the receptor element 209. Preferably, this layer 210 may provide a physical and chemical environment that may be suitable for the function of the sensor device 100, e.g., providing a conductive bridge 110a-c between the working and counter electrodes. Furthermore, the layer 210 may resemble the surface of a cell culture cultivated at the ALI, e.g., with respect to solvent polarity, surface tension, and / or pH. In this case, the layer 210 may be considered as part of the receptor element 209, and the dimensions of the measurement compartment 102 must take into account the thickness Δh of this liquid layer 210, the thickness of the receptor element 209, the thickness of the receptor support 104, and the thickness of the electrode array 110 or the transducer element 106, so that the position of the surface 203 of the receptor element 209 can be matched with the position of the cell culture surface 206 with respect to the geometry of the exposure chamber. Thus, the height of the sensor device 100, measured from the bottom end 103 to the top end 105, may be greater than the height of a standard cell culture insert 201 by the sum of the thicknesses of the substrate layer 210, the receptor element 209, the electrode array 110, and the receptor support 104. In other words, the height of the standard transwell cell culture insert 201 and the height of the sensor device 100 or its measurement compartment 102 may differ by Δh, which may be the sum of the thicknesses of the receptor support 104, the transducer element 1906, the receptor element 209, and the liquid or gelatinous substrate layer 210 that may be present on the receptor element 209.

[0114] Generally, the sensor device 100 may exhibit similar physicochemical properties, e.g. with respect to adsorptive and / or electrostatic properties, to those exhibited by the actual cell culture insert 201. Therefore, the measurement compartment 102 is preferably made from the same materials as standard transwell cell culture inserts, which typically comprise polystyrene.

[0115] As shown in FIG. 2, the sensor device 100 may comprise a sensing surface 203 substantially aligned with a sensing surface of a cell culture in a standard cell culture insert 201. In FIG. 2, the two inserts are shown as they would be placed in a typical in vitro aerosol exposure system 500, where the exposure trumpet 204 protrudes into the cell culture insert 210 or into the measurement compartment 102 to bring a test atmosphere containing one or more components 111 to be investigated in close proximity to the cell culture surface and / or the sensing surface 203. In FIG. 2, the airflow paths are indicated by arrows, and the test atmosphere or its components are indicated by dots 111. An exposure chamber housing that may surround the insert 201 and the sensor device 100, as well as a cell culture medium that may be placed below the insert 201, are omitted in FIG. 2 (see FIG. 3).

[0116] As mentioned above, the bottom of the standard cell culture insert 201 is a porous membrane 205 on which the cell culture 206 is cultured, whereas the bottom wall 109 of the sensor device 100 provides a closed surface 109 on which the electrode array 110 and / or transducer elements 106 are disposed.

[0117] As mentioned above, the height of the standard cell culture insert 201 and the height of the sensor device 100 or its measurement compartment 102 may differ by Δh, which may be the sum of the thicknesses of the receptor support 104, the transducer element 106, the receptor element 209, and the liquid or gelatinous substrate layer 210 that may be present on the receptor element 209. The vertical position of the surface 203 to which the exposure takes place and the corresponding surface of the cell culture 206 in the standard cell culture insert 201 may be identical in the two configurations, and the thickness of the cell culture 206 and the porous PET membrane 205 in the standard transwell cell culture insert 201 can be neglected. Moreover, therewith, the distance between the surface 203 to be exposed (or the corresponding surface of the cell culture 206) and the exposure trumpet 204 may be the same in both configurations. If desired, all other aspects of the geometry of the cell culture insert 201 may be similar or identical to the measurement compartment 102, such that the flow patterns and deposition rates of the test atmosphere may be the same or similar, and the dose delivery to the cell culture and to the sensor device 100 may also be the same or at least very similar. Thus, the measurements of the sensor device 100 allow for an accurate determination of the dose associated with the exposure of the cell culture to the test atmosphere.

[0118] Depending on the type of component 111 to be investigated and also depending on the spectrum or range of components to be coated, the sensor device 100 can be adapted, for example, with respect to the type of receptor element 209 or receptor element 209 selected. Furthermore, the sensor device 100 can be adapted depending on the required selectivity and sensitivity, as well as the physical and chemical environment in which it operates. Thus, the sensor device 100 described herein can provide a highly adaptable and modular sensor system.

[0119] A preferred embodiment or example may comprise an electrochemical sensor, the receptor element 209 of which may be a molecularly imprinted polymer (MIP). The receptor support 104 on which the MIP is deposited, i.e. the bottom wall 109 of the measurement compartment 102, may comprise an electrode array 110 with working electrode 110c, counter electrode 110b and reference electrode 110a, which connect to a power source 118, a processing device 120, e.g. a voltmeter, ammeter or impedance meter, and a processing circuit with one or more processors for data processing. It is preferred that the MIP is deposited directly on the electrodes 110a-c. Electrical connections to the power source 118 and / or the processing device 120 may be present in the wall of the measurement compartment 102. The electrodes 110a-c and electrical connections 114 may for example be glued or printed in / onto the measurement compartment 102.

[0120] For sustainability reasons, the sensor device 100 may be reusable. The MIP can be regenerated several times, i.e. the bound target molecules can be removed from the MIP, for example by washing with an appropriate solvent. Furthermore, if the specificity and / or selectivity of the MIP decreases after several regeneration cycles, the MIP can be removed from the surface of the receptor support 104 and a new MIP can be deposited on it. Although polystyrene may be resistant to the most common chemical and physical procedures used for the deposition, regeneration and removal of MIPs, in order to maintain reusability, other, more resistant materials, for example stainless steel, Teflon, PEEK measurement compartment 102, or measurement compartment 102 coated with, for example, gold, platinum or Teflon, may be used for special applications.

[0121] In the following, possible materials and dimensions for one or more components of the sensor device 100 are exemplarily summarized. The measurement compartment 102 may comprise any material that can be shaped as desired and has at least the stability of a real cell culture vessel of a standard cell culture insert 201. Preferably, the same material as the commercially available transwell insert 201 is used, e.g. polystyrene, since this may allow the simulation of unexpected material effects, e.g. related to adsorption. Porous materials or materials with a large surface area, e.g. rough structure, should be avoided, since they may increase the loss of the test atmosphere components. Furthermore, for a reusable sensor device 100, stainless steel or other materials, e.g. PEEK, which are not sensitive to solvents or heat (washing / autoclaving), may be considered.

[0122] For any receptor element 209, it is preferred that a receptor element 209 compatible with electrochemical detection is used, such as a molecularly imprinted polymer, an antibody, a receptor protein, or an enzyme.

[0123] Gold, platinum, or glassy carbon may be selected for the electrodes 110a-c, transducer elements 106, leads 112, and / or interface 114. To maintain a wide range of applications and the possibility to regenerate and replace the receptor element 209, the electrodes 110a-c may be inert to weak acids and bases, biological fluids, and weak organic solvents.

[0124] The internal dimensions of the measurement compartment 102 may correspond to the shape and dimensions of commercially available transwell cell culture inserts 201 in the form of standard 24, 12 or 6 wells. If the sensor device 100 is configured for a liquid environment, in particular as in the case of an electrochemical sensor and corresponding receptor element 209, the sensor device 100 may be provided with a certain additional volume, in particular a greater depth or height, compared to the standard insert 201. In this case, the measurement compartment 102 and / or the sensor device 100 may be slightly deeper than the actual cell culture vessel of the standard insert 201 in order to bring the surface of the liquid or gelatinous substrate 210 into a position equivalent or corresponding to the cell culture surface (see FIG. 2). Also, the external dimensions of the sensor device 100 and / or the measurement compartment 102 are preferably close to the dimensions of the standard insert 201, which may ensure compatibility with the majority of exposure systems 500 for which the sensor device 100 can be used.

[0125] The electrical leads 112 and electrodes 110 a - c may be adapted to a size corresponding to the size of the measurement zone 102 .

[0126] In embodiments with electrical contacts 114 or interface 114, for example when no wires are connected to the top edge 105 of the measurement compartment 102 or to the interface 114, the connection to the power supply 118 and / or the processing device 120 may be established by plugging a wire or holder for post-readout directly into the top edge of the measurement compartment 102. The contacts should not interfere with the insertion of the measurement compartment 102 into the exposure system 500 or cell culture plate, and therefore preferably protrude as little as possible from the measurement compartment 102. In embodiments where wires are attached to the top edge of the sensor device 100 or the measurement compartment 102, the wires are preferably about 25 cm long to bridge the gasket that seals the exposure chamber of commonly used aerosol exposure systems 500 from the environment and to facilitate handling of the connection outside the exposure system 500. The wires must be as thin as possible so as not to interfere with the airtightness of the system and are preferably designed as foil cables.

[0127] FIG. 3 illustrates an aerosol exposure system 500 that includes one or more sensor devices 100, such as one or more of the sensor devices 100 described with reference to FIGS.

[0128] The aerosol exposure system 500 includes an opening 502 through which the sensor device 100 may be inserted into an exposure chamber 504 of the system 500 .

[0129] 3, one or more sensor devices 100 may be disposed in one or more wells of a multi-well or 6-well cell culture plate 510. Other configurations of culture plates, for example 12 or 24-well plates, may alternatively be used.

[0130] The exposure system 500 may further include one or more exposure trumpets 204, as illustrated in FIG.

[0131] Additionally, the exposure system 500 may include a power source 118 or supply 118 and / or a processing unit 120 for data processing, which may be communicatively and operably coupled to one or more sensor devices 100.

[0132] FIG. 4 is a flow chart illustrating a method for determining in vitro exposure of a cell culture surrogate, such as liquid and / or gelatinous cell culture medium, to a test atmosphere containing one or more components 111 of interest.

[0133] In step S1, a sensor device 100 is provided, for example the sensor device 100 described with reference to Figures 1 and 2.

[0134] Step S2 involves placing the receptor element 209 of the electrochemical sensor in the measurement compartment 102 of the sensor device 100. Optionally, the sensor device may be placed in an exposure chamber 504 of the exposure system 500.

[0135] Step S3 involves exposing the sensor device 100 and the receptor element 209 to a test atmosphere, for example in the exposure chamber 504 of the exposure system 500.

[0136] Further, step S4 includes using the transducer element 106 of the sensor device 100 to generate an electronically processable signal indicative of one or more components 111 of the test atmosphere.

[0137] If desired, the generated signal may be processed in the sensor device 100 or the processing unit 120 of the aerosol exposure system 500, and the exposure may be quantified, for example, based on determining a measurement value that correlates with a dose associated with one or more components of the test atmosphere.

[0138] While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description is exemplary or representative and not restrictive, and the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art and by the practice of the invention, from a study of the drawings, the disclosure, and the appended claims.

[0139] In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be interpreted as limiting their scope.

Claims

1. 1. A sensor device for an aerosol exposure system for in vitro exposure of a cell culture to a test atmosphere, the sensor device comprising: a measurement compartment configured to receive a receptor element of an electrochemical sensor for detecting one or more components of the test atmosphere; a receptor support disposed at an end of the measurement compartment and configured to support the receptor element of the electrochemical sensor; a transducer element operably couplable to the receptor element and configured to provide an electronically processable signal indicative of the one or more components in the test atmosphere.

2. The sensor device of claim 1 , wherein the measurement compartment defines an interior space, in particular a cylindrical interior space, of the sensor device configured to circumferentially at least partially surround the receptor element of the electrochemical sensor.

3. 3. The sensor device according to any one of claims 1 to 2, wherein the measurement compartment and the receptor support together form a cavity of the sensor device, the cavity being configured to hold a substrate that mimics a surface of a cell culture, such as a cell culture medium, in particular a liquid and / or gelatinous cell culture medium, or another liquid, gelatinous, polymeric and / or porous material that mimics the surface of the cell culture.

4. 4. The sensor device according to claim 1, wherein the measurement compartment and / or the sensor device are sized, shaped and formed to correspond to the interior space of an exposure chamber and / or a well of a culture plate, in particular a 6, 12 or 24 well cell culture plate, such that the receptor support and / or the receptor element of the electrochemical sensor can be positioned at a predetermined position within the exposure chamber and / or within the well of the cell culture plate.

5. 5. A sensor device according to claim 1, wherein the receptor support is arranged and / or configured to position the receptor element relative to a transducer element such that functional contact between the transducer element and the receptor element of the electrochemical sensor is established.

6. A sensor device according to any one of claims 1 to 5, wherein at least a portion of the transducer element is integrated into and / or embedded within the receptor support.

7. A sensor device according to any one of claims 1 to 6, wherein at least some of the transducer elements are attached to a side of the receptor support facing an interior space defined by the measurement compartment.

8. 8. The sensor device according to claim 1, wherein the transducer element comprises an electrode array arranged on a side of the receptor support facing the measurement compartment, the array preferably comprising a working electrode, a counter electrode and a reference electrode.

9. 9. The sensor device of claim 1, further comprising at least one receptor element of an electrochemical sensor configured to physically and / or chemically interact with the one or more components of the test atmosphere.

10. A sensor device according to any one of claims 1 to 9, wherein the receptor element comprises at least one of a molecular imprinted polymer, an antibody, a receptor protein and an enzyme configured to interact with one or more components in the test atmosphere, and preferably the receptor element comprises a layer of at least one of a molecular imprinted polymer, an antibody, a receptor protein and an enzyme configured to interact with the one or more components in the test atmosphere.

11. 11. A sensor device according to any one of claims 1 to 10, further comprising one or more leads contacting the transducer elements for electrical supply and / or for transmitting the electronically processable signal to a processing device.

12. The sensor device according to any one of claims 1 to 11, further comprising a holder configured to receive at least a portion of the measurement zone.

13. The sensor device of claim 12 , wherein the holder comprises an interface configured to establish an electronic connection with the transducer element upon receipt of the measurement section within the holder.

14. 14. The sensor device of claim 1, further comprising a processing unit configured to process the electronically processable signals provided by the transducer elements into a measurement value that correlates with a dose associated with the one or more components of the test atmosphere.

15. Use of a sensor device according to any one of claims 1 to 14 for determining the exposure of a cell culture to a test atmosphere, in particular for dose assessment.

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