Detection of biologically active substances in ambient media

Abstract

A sensor chip operably connectable to a detection device for detecting one or more biologically active substances in a surrounding medium is proposed, the sensor chip comprising a reaction cell containing a plurality of receptor protein complexes and a membrane separating the reaction cell from the surrounding medium and permeable to the one or more biologically active substances, the receptor protein complexes being configured to bind to the one or more biologically active substances in the reaction cell, thereby inducing a detectable state change in at least a portion of the receptor protein complexes.

Description

[Technical Field]

[0001] The present disclosure generally relates to the detection of biologically active substances. In particular, the present disclosure relates to a sensor chip that can be coupled to a detection device, and the detection device for detecting one or more biologically active substances in a surrounding medium. The present disclosure further relates to a detection system that includes such a sensor chip and detection device. The present disclosure also relates to uses of the sensor chip, detection device, or detection system, and methods of detecting one or more biologically active substances with the sensor chip, detection device, or detection system. [Background technology]

[0002] Humans, animals, or organisms generally constantly interact with their chemical environment. For example, organisms are usually exposed to or in contact with surrounding media, such as the surrounding air or water, and may receive, ingest, absorb, or otherwise incorporate molecules, agents, or compounds from the surrounding medium, thereby interacting with their chemical environment. Interactions involving specific molecules, agents, or compounds from the surrounding medium may be desirable or even necessary for the organism's survival. Examples of such interactions include oxygen inhaled by humans or animals and binding to hemoglobin in red blood cells passing through pulmonary capillaries, or sugar molecules selectively transported across the intestinal epithelium. However, chemical interactions with the surrounding medium involving other molecules, agents, or compounds may not be part of normal life-sustaining processes and may have undesirable effects and even harm the organism. Such undesirable effects may be caused by molecules, agents, or compounds received by the organism from the surrounding medium, which nonspecifically damage the molecular building blocks of cells or whole cells. For example, when absorbed by an organism, oxidizing compounds such as ozone can oxidize the organism's biomolecules, such as proteins, lipids, or nucleic acids, and reduce or even destroy their biochemical and / or structural functionality. Alternatively, chemical compounds, agents, or molecules absorbed by an organism can activate, inhibit, or even eliminate certain biochemical processes in the organism, often without chemically altering the organism's biomolecules. Examples of such processes or interactions include the inhibition of the enzyme cyclooxygenase by ibuprofen or the activation of nicotinic acetylcholine receptors by nicotine. Typically, such interactions depend on the structural identity between the affected biomolecule and the effector molecule, agent, or compound. For example, ibuprofen binds to the active site of cyclooxygenase, thereby preventing the binding of arachidonic acid, which is normally converted by cyclooxygenase into signaling molecules involved in the development of inflammation and pain.

[0003] Living organisms have developed and evolved mechanisms to detect harmful chemical compounds, agents, or molecules to which they are exposed and to induce appropriate physiological responses. Chemical compounds, agents, and molecules that induce physiological responses in living organisms may generally be referred to herein as bioactive agents. Various receptor proteins have been identified in humans and other organisms that are useful for detecting bioactive agents and inducing physiological responses. Important examples of receptor proteins include the aryl hydrocarbon receptor (AHR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR). These receptor proteins exhibit certain binding specificities for bioactive agents related to bioactive substances, compounds, or molecules that are foreign to the living system, particularly so-called xenobiotics. On the other hand, there are various receptor proteins that have not evolved to detect and protect against potentially harmful but rather important bioactive agents, such as xenobiotics, as part of regulatory systems. For example, the endocrine or hormonal system controls various developmental and steady-state functions in animals or humans, including growth, organogenesis, fertility, reproduction, and sleep. These receptor proteins specifically bind to and are activated by their cognate ligands, which are hormones. However, bioactive substances that share certain structural features with hormones can also bind to and activate these receptors. This process can be called endocrine disruption and, given the important role of the endocrine system, can have deleterious effects. For example, exposure to xenoestrogens, which are bioactive substances or xenobiotic compounds that activate the estrogen receptor (ER), has been linked to the development of breast, lung, kidney, pancreatic, and brain cancers, not by directly or indirectly damaging genetic material, but by activating cell signaling cascades at the wrong time and / or place in the body.

[0004] Various devices, systems, and instruments for detecting components of ambient media, as well as corresponding sensors, have been developed over the past few years. The detection of components in a medium or ambient medium can also be referred to as environmental monitoring. Generally, environmental monitoring refers to the characterization of the state or quality of a ambient medium or environment over time, and can be performed, for example, to ensure that the chemical composition of the environment or ambient medium does not pose a risk to human or animal health.

[0005] Detection of components in ambient media or environmental monitoring can be an important tool used to identify and quantify the impact of human activities on the natural environment, typically soil, water, air, or ecosystems, for example, to estimate the risks resulting from such impacts and develop strategies for their reduction or elimination. Environmental monitoring can be carried out on a global scale, such as monitoring climate change or marine microplastic pollution, on a regional scale, such as monitoring the pollution of a specific river, or on a local scale, such as monitoring the air quality at an industrial facility or the water quality at a fish farm. Local environmental monitoring is often carried out to ensure compliance with regulatory guidelines at industrial or agricultural facilities. The ultimate goal is to maintain the safety of employees, nearby residents, and the environment by detecting and removing emissions, thereby reducing exposure and thus associated risks. Such monitoring can be carried out in a targeted manner, since the nature of expected emissions is usually well known. For example, antibiotic residues in water can be observed or detected in close proximity to a fish farm. In agricultural areas, pesticide residues in groundwater and / or river water may be of concern, and near oil refineries, concentrations of volatile hydrocarbons in the ambient air may be monitored and used as an indicator of product leakage at any stage of the refining process.

[0006] However, environmental monitoring or detection of components of ambient media generally may also be utilized for personal or individual applications, such as for monitoring a person's civilian or personal environment, for example, dust, pollen and / or fungal spores, volatile organic carbons (VOCs), nitric oxide (NO ), and the like. x ) or UV radiation concentrations can be measured in the air in close proximity to a person or individual who has a corresponding detection device at home or in, for example, a car, or attached to an item of luggage such as a backpack or handbag. The goal of such applications may typically be to reduce personal exposure by avoiding exposure rather than by eliminating the source, which can be difficult to achieve, for example, in the case of UV, pollen, or ozone exposure. In particular, in such individual or personal applications of environmental monitoring, it can be difficult to detect unknown or undefined pollution sources. For example, obtaining a comprehensive estimate of the current local quality of the environment or surrounding medium can be difficult, for example, by monitoring particulate matter, VOCs, NO, and other pollutants. x It may be necessary to simultaneously monitor a variety of environmental parameters such as ozone, UV, electrosmog and ionizing radiation.

[0007] To this end, various devices and corresponding sensors have been developed over the past few years. Some of these devices and sensors can simultaneously monitor multiple environmental parameters, enabling real-time tracking of air quality, including location- and time-specific predictions of air pollution, for example, for optimal route planning. However, these known or conventional devices for environmental monitoring are usually limited in that the detection modes or sensors utilized are either highly selective or largely unselective. For example, NO xKnown exogenous pathogenic toxins, such as chlorophyll, carbon monoxide, or ozone, can be selectively detected using sensitive and highly selective electrochemical or spectroscopic sensors. While these highly selective sensors can provide valuable information about the concentration of specific molecules, agents, or compounds of interest in the ambient medium, they may not detect other potentially harmful molecules, agents, or compounds, especially if the respective molecules, agents, or compounds are unknown. On the other hand, a common type of non-selective sensor used in environmental monitoring is a VOC sensor, which relies on photoionization and detects any organic molecule that is ionized by light of a given frequency or energy. However, the ionization potential of an organic molecule may not be related to its toxicity or biological activity. As an example, pinene, a plant-derived terpene responsible for the characteristic odor of pine trees, and 1,1-dimethylhydrazine, a rocket propellant, have virtually identical ionization potentials of 8.07 eV and 8.05 eV, respectively, and both are ionized by UV light or energy of a sufficiently high frequency, approximately 8 eV. However, their acute toxicity or biological activity differs significantly. On the other hand, acetaldehyde, a carbonyl compound frequently used in chemical synthesis, has an ionization potential of 10.2 eV and therefore has significant acute toxicity or biological activity, even though it is not detected by VOC sensors operating at approximately 8 eV.

[0008] As is evident from the foregoing examples, devices employing highly selective sensors may fail to detect various compounds, agents, or molecules that cannot be detected by the sensor but may potentially have adverse effects on human health. Therefore, when utilizing highly selective sensors, the number of false negatives may be quite high. On the other hand, devices employing non-selective sensors may provide readings with limited health relevance, which may result in a high number of false positives. In addition, devices with non-selective sensors may also fail to detect other compounds, molecules, or agents that may have adverse effects on human health, which may result in a high number of false negatives. In other words, while devices with non-selective sensors may detect a broad group of compounds, molecules, or agents that share certain common physicochemical properties, the devices may be unable to distinguish molecules, compounds, or agents that may pose a health risk from molecules, compounds, or agents that do not pose a health risk.

[0009] It would therefore be desirable to provide improved devices, systems, instruments and methods for detecting one or more biologically active substances in a surrounding medium, for example, that report a reduced number of false positives and / or false negatives.

[0010] 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

[0011] Aspects of the present disclosure relate to sensor chips, detection devices, detection systems, uses of one or more of the foregoing, and methods for detecting one or more biologically active substances in a surrounding medium. Any disclosure provided herein above and below with reference to one aspect of the present disclosure applies equally to other aspects of the present disclosure.

[0012] According to one aspect of the present disclosure, a sensor chip operably connectable to a detection device for detecting one or more biologically active substances in a surrounding medium and / or a medium surrounding the sensor chip is provided. The sensor chip includes a reaction cell containing a plurality of receptor protein complexes and a membrane separating the reaction cell from the surrounding medium and permeable to the one or more biologically active substances. The receptor protein complexes are configured to bind to the one or more biologically active substances in the reaction cell, thereby inducing a detectable state change in at least a portion of the receptor protein complexes.

[0013] As will be further elucidated below, utilizing a receptor protein complex within the reaction cell that can bind to a bioactive substance that enters the reaction cell from the surrounding medium can enable the detection of bioactive substances in their surrounding medium by leveraging the advanced and sophisticated capabilities of living organisms. As a result, the number of false positive and false negative events detected or reported by the sensor chips, detection devices, and / or detection systems of the present disclosure can be significantly reduced, thereby enabling comprehensive, reliable, and accurate detection of bioactive substances in the surrounding medium.

[0014] A reaction cell of a sensor chip may refer to or denote a compartment or chamber that contains or includes a receptor-protein complex, and the reaction cell may have at least a portion, section, or region separated from the surrounding medium by a membrane. The reaction cell may have any suitable size, shape, geometry, form, or volume.

[0015] The membrane may generally be permeable to one or more biologically active substances to be detected by the sensor chip. For example, the membrane may allow for exchange of substances between the reaction cell and the surrounding medium. In particular, the membrane may be positioned and configured to allow one or more biologically active substances to pass through the membrane from the surrounding medium into the reaction cell, for example, by diffusion.

[0016] As used herein, a bioactive substance may refer to a molecule, agent, or compound that can induce a physiological response in an organism, such as a human or animal, upon binding to a receptor protein in the organism that is the same as or equivalent to the receptor protein complex of the sensor chip. In this regard, inducing a physiological response may include inducing a cellular defense mechanism or a cellular response in the organism. Alternatively, or additionally, inducing a physiological response may include one or more of activating, inhibiting, and eliminating a biochemical process in the organism.

[0017] For example, a bioactive substance that is taken up by an organism and binds to a hormone receptor protein of the organism may activate a cellular response in the absence of endogenous signaling activity, as described hereinabove. Because a bioactive substance induces a physiological response in an organism, it is usually also associated with or involves a particular toxicity or health risk to the organism. Therefore, by detecting one or more bioactive substances using the sensor chip of the present disclosure, the toxicity or contamination of the surrounding medium can be reliably determined or evaluated.

[0018] As used herein, receptor protein complexes generally refer to or may refer to functional complexes configured to bind to one or more biologically active substances and undergo a change in their state upon binding, which may be detected or measured by a sensor chip. In this regard, each receptor protein complex may include at least one ligand-binding domain configured to bind to at least one biologically active substance, which may also be referred to as a ligand in this context. For example, each receptor protein complex may include at least one ligand-binding domain of a receptor protein that may be present in an organism with a similar, identical, or equivalent structure, sequence, or morphology.

[0019] Thus, a state change induced by the binding of one of the receptor protein complexes of the sensor chip to at least one bioactive substance can reflect, resemble, or be suggestive of a cellular or physiological response induced when the bioactive substance binds to an equivalent or similar receptor protein in an organism. Thus, when a state change is detected or determined by the sensor chip, it can be inferred that the bioactive substance will induce a physiological response in the organism. Therefore, a sensor chip according to the present disclosure can provide a significant advantage over sensors that nonselectively respond to a wide range of compounds based on specific structural properties that may not be related to the compound's biological activity, such as in the case of VOC sensors. Furthermore, it should be noted that the chemical structure and source of a bioactive substance bound to one of the receptor protein complexes may be unknown. Therefore, a sensor chip according to the present disclosure can also provide a significant advantage over sensors that selectively and exclusively detect known bioactive substances, such as pathogenic toxins.

[0020] The binding of the receptor protein complex may result in, be accompanied by, or be accompanied by various types of state changes of the receptor protein complex, including changes in conformation, structure, shape, position, localization, composition, chemical reactivity, chemical activity, and the like. Alternatively, or additionally, the state change induced in the receptor protein complex may result in deformation or change of at least a portion of the reaction cell and / or membrane. These various state changes of the receptor protein complex and / or the deformation or change of at least the components of the sensor chip associated therewith can be detected by different approaches, for example, using detection principles or detection modes. As will be described in detail below, all of these different detection principles are contemplated in the context of the present disclosure.

[0021] In one example, the change in state of at least a portion of the receptor protein complex can involve a change in the conformational state of at least a portion of the receptor protein complex. For example, the receptor protein complex can be in its native state within the reaction cell and configured to undergo a conformational change upon binding to one of the biologically active agents.

[0022] Alternatively, or in addition, the change in state of the receptor complex may involve a change in the localization and / or position of at least a portion of the receptor protein complex within the reaction cell. Thus, the receptor protein complex may be configured to change its position and / or localization within the reaction cell upon binding to one or more biologically active substances. The change in position may involve or include movement of each protein complex, or at least a portion thereof, within the reaction cell. Such a change in position and / or localization may be induced, for example, by a change in conformation of the receptor protein complex or of another ligand bound to the receptor protein complex.

[0023] Alternatively, or additionally, the change in state can involve a change in the composition of at least a portion of the receptor protein complex. For example, the composition of the receptor protein complex can change upon binding to a biologically active agent based on dissociation or exchange of components or portions of the receptor protein complex, or by binding to another component or portion of the receptor protein complex. Thus, the receptor protein complex can be configured to dissociate into one or more components upon binding to one or more biologically active agents, can be configured to exchange one or more components upon binding to one or more biologically active agents, and / or can be configured to bind to one or more moieties upon binding to one or more biologically active agents.

[0024] Optionally, the change in composition of at least a portion of the receptor protein complex can be accompanied by a change in mass of at least a portion of the receptor protein complex, for example, if one or more moieties are released upon binding to a biologically active agent. Alternatively, or additionally, a change in mass of at least a portion of the reaction cell and / or membrane can be accompanied by an induced state change and can be detected by the sensor chip.

[0025] Furthermore, the induced state change may involve one or more of a change in a physical property of at least a portion of the receptor protein complex, a change in a physical property of at least a portion of the reaction cell and / or membrane, a change in an optical property of at least a portion of the reaction cell and / or membrane, a change in a chemical property of at least a portion of the receptor protein complex, a change in a chemical property of a substrate contained within the reaction cell, a change in the electrical conductivity of a substrate contained within the reaction cell, or a change in the concentration of free fluorescent or light-absorbing molecules within at least a portion of the reaction cell.

[0026] Any one or more of the aforementioned state changes and / or deformations or changes of at least a portion or component of the sensor chip can be used to reliably detect the presence of one or more biologically active substances in the surrounding medium. Thus, one or more detectable state changes of at least a portion of the receptor-protein complex can be indicative of the presence of one or more biologically active substances in the surrounding medium.

[0027] For example, at least a portion of the receptor protein complex can be bound or immobilized to at least one functional surface of the reaction cell, and at least a portion of the receptor protein complex can be configured to dissociate from the at least one functional surface upon binding to one or more biologically active substances. In other words, at least a portion of the receptor protein complex bound or immobilized to the at least one functional surface can be released or liberated from the at least one functional surface upon binding to one or more biologically active substances. Dissociation from the at least one functional surface can result in or involve, for example, one or more of the following: a change in the mass of the at least one functional surface, membrane, or other inner surface of the reaction cell; a change in the optical properties of the at least one functional surface, membrane, or other inner surface or substrate included in the reaction cell; and a change in another property or characteristic of one or more of the functional surface, membrane, and reaction cell. Any one or more of these changes can be detected by a sensor chip and can enable accurate detection of one or more biologically active substances.

[0028] As an example, at least a portion of the receptor protein complex can be covalently bound to at least one functional surface of the reaction cell. Thus, at least a portion of the receptor protein complex can be bound or immobilized on at least one functional surface based on covalently binding the receptor protein complex to the at least one functional surface. For example, at least a portion of the receptor protein complex can be bound or immobilized on at least one functional surface of the reaction cell by a ligand, e.g., a low-affinity ligand or a high-affinity ligand, covalently bound to the at least one functional surface of the reaction cell. In this case, at least a portion of the at least one functional surface can include or be coated with the ligand. Both low-affinity and high-affinity ligands can be used, but low-affinity ligands can provide a stronger signal compared to high-affinity ligands.

[0029] Alternatively, or additionally, the receptor-protein complex can be electrostatically bound to at least one functional surface of the reaction cell. This can include, for example, ionic bonding or binding through weak interactions such as van der Waals forces. Electrostatic binding can be provided passively, for example, based on an electrical charge carried by at least one functional surface, or actively, for example, based on charging one or more electrodes of a sensor chip at or near at least one functional surface.

[0030] At least one functional surface of the reaction cell may be defined by an inner surface of the membrane facing the reaction cell, in other words, an inner surface of the membrane facing or directed towards the interior of the reaction cell may constitute at least one functional surface.

[0031] Alternatively or additionally, the at least one functional surface may include an inner surface of the reaction cell, the inner surface being disposed toward the membrane. An inner surface being disposed toward the membrane may mean that the surface normal vector of the inner surface and the surface normal vector of the membrane are oriented transversely relative to each other. For example, the at least one functional surface may include an inner surface of the reaction cell disposed opposite or adjacent to the membrane.

[0032] In one embodiment, the ambient medium may include ambient air, atmospheric air, or air in the environment or surroundings of the sensor chip. Accordingly, the sensor chip of the present disclosure may be configured to detect one or more bioactive substances in ambient air. Thus, the sensor chip may be utilized, for example, for environmental monitoring and / or monitoring of ambient air quality.

[0033] Alternatively, the surrounding medium may include water. Accordingly, the sensor chip of the present disclosure may be configured to detect one or more biologically active substances in water. Accordingly, the sensor chip may be utilized for environmental monitoring and / or monitoring of water quality, for example, surface water, groundwater, ocean water, river water, fish farm water, pool water, etc. It should be noted that the sensor chip according to the present disclosure may also be advantageously utilized to detect one or more biologically active substances in other media or materials, such as soil.

[0034] The membrane can include an outer surface configured to contact the surrounding medium and can include an inner surface facing the reaction cell. Thus, the outer surface of the membrane can face toward the surrounding medium and the inner surface of the membrane can face toward the interior of the reaction cell. At least during use of the sensor chip, the outer surface of the membrane can be configured to be in constant contact with the surrounding medium, thereby allowing the surrounding medium to be constantly monitored for the presence of one or more biologically active substances.

[0035] In one embodiment, the reaction cell can contain one or more of a liquid, gelatinous, and semi-solid substrate. In that regard, the reaction cell can be partially or completely filled with the substrate. For example, the substrate can be configured such that the receptor protein complex remains in its native state, particularly when not bound to one or more biologically active substances. By providing such a liquid, semi-solid, and / or gelatinous substrate within the reaction cell, the lifetime of the receptor protein complex, and thus the lifetime of the sensor chip, can be significantly increased.

[0036] By way of example, the substrate may comprise at least one of an aqueous solution, an isotonic solution, and a buffer solution. Thus, the reaction cell may contain an aqueous liquid, an isotonic liquid, a buffer solution, a gelatinous and / or semi-solid substrate, such as a gelatinous matrix, in which the receptor-protein complex and any additional proteins that may be present in the reaction cell maintain their native state.

[0037] Optionally, the substrate may include a stabilizing protein to stabilize the receptor protein complex, e.g., in their native state. Alternatively, or additionally, the substrate may include a surfactant molecule or surfactant molecule complex, e.g., one or more of Tween or Triton X-100.

[0038] The membrane of the sensor chip can be gas-permeable. Gas-permeability of the membrane can be particularly advantageous when the surrounding medium contains or includes air that can cross the membrane and enter the reaction cell through the membrane. Alternatively, or additionally, the membrane can be impermeable to water or aqueous liquids. The impermeability of the membrane to water or aqueous liquids can prevent leakage of the substrate or other liquids out of the reaction cell, thereby ensuring the functionality of the sensor chip and increasing its lifespan.

[0039] In one embodiment, the membrane may comprise a plurality of pores, preferably filled with gas to exclude water, such that the membrane is gas permeable while effectively ensuring impermeability to water or aqueous liquids over an extended lifetime of the sensor chip.

[0040] For example, the membrane may comprise at least one of a porous carbon paper material and a perforated fluoropolymer, although it should be noted that the membrane may also comprise other materials or polymers, including lipids.

[0041] In further embodiments, the sensor chip may further comprise a grid covering at least a portion of the outer surface of the membrane. The grid may be positioned and configured to protect the membrane and / or the reaction cell from external physical damage. The grid may be a rigid open grid. The grid may be integrally formed with the housing of the sensor chip or may be formed as a separate part or member attached to the housing of the sensor chip.

[0042] Alternatively or additionally, the sensor chip may further include a sealing cover configured to cover at least a portion of the outer surface of the membrane and prevent the membrane from contacting the surrounding medium. The sealing cover may be in direct contact with the membrane or may be spaced apart from the membrane. For example, the sealing cover may be disposed on the outer surface of a lattice that covers at least a portion of the outer surface of the membrane. In particular, the sealing cover may be used to cover the outer surface of the membrane and block the entry of biologically active substances into the reaction cells when the sensor chip is not in operation. This can increase the service life or lifetime of the sensor chip, because the amount of receptor-protein complexes in the reaction cells may decrease over time if not covered by the sealing cover.

[0043] Generally, the sealing cover may be single-use only, or the sealing cover may be reused to cover the membrane. Thus, the reaction cell may be sealable and / or resealable by covering at least a portion of the outer surface of the membrane with the sealing cover.

[0044] In one embodiment, the sealing cover may include, for example, an adhesive film that allows the sealing cover to be removably attached or stuck to the sensor chip. For example, the adhesive film may be disposed on at least a portion of the surface of the sealing cover, for example around the periphery of the surface, allowing the sealing cover to be securely attached to the sensor chip and ensuring that the membrane or reaction cell is comprehensively sealed to the surrounding medium by the sealing cover. However, it should be noted that other means of attaching the sealing cover to the sensor chip may also be used, including magnetic coupling as well as snap-fit connections or other mechanical couplings.

[0045] The sealing cover may be airtight and / or configured to block air from passing through it. The airtight configuration and attachment of the sealing cover to the sensor chip can ensure that surrounding media or biologically active substances, which may reduce the number of receptor-protein complexes in the reaction cell over time, cannot enter the reaction cell. As mentioned above, this sealing of the reaction cell can be particularly advantageous when the sensor chip is not in operation, such as when the sensor chip is being stored.

[0046] The sensor chip can be configured with a shape and size to be at least partially inserted into the detection device. Thus, the sensor chip can be shaped and sized to be at least partially inserted into the detection device. Such partial insertion can ensure proper positioning of the sensor chip within the detection device, can ensure proper connection or coupling between the sensor chip and the detection device, and can protect the sensor chip from damage.

[0047] For example, the sensor chip can be configured with a shape and size such that it can be at least partially inserted into a socket of the detection device. In other words, the detection device can include at least one socket that at least partially receives the sensor chip. The socket can be shaped, for example, slot-like, and the sensor chip can be inserted into the socket by pushing the sensor chip into the socket.

[0048] Optionally, the sensor chip may include at least one surface feature on an outer surface of the sensor chip housing, the at least one surface feature of the sensor chip being complementary to the at least one surface feature of the socket to ensure correct positioning of the sensor chip within the socket, wherein the at least one surface feature of the sensor chip may optionally be configured to engage with the at least one surface feature of the socket to secure the sensor chip within the socket. Thus, the surface feature of the socket and the surface feature of the sensor chip housing may provide a click-fit or snap-fit mechanism for securing the sensor chip within the socket.

[0049] Alternatively, or additionally, the sensor chip may include one or more magnets or magnetic elements for magnetically coupling the sensor chip to the detection device, and other means for fastening the sensor chip to the detection device, such as screw fastening or other mechanical fastening, may also be used.

[0050] As described above, one or more different detection principles or configurations can be applied to detect a state change of at least a portion of a receptor protein complex induced by binding to one or more biologically active substances. For example, the state change of at least a portion of the receptor protein complex can be detectable based on optical measurements. Such optical measurements can be performed within at least a portion of the reaction cell, on at least a portion of the membrane, or outside the reaction cell. Alternatively, or additionally, the state change can be detectable based on detection of fluorescent light and fluorescence excitation of one or more components of the receptor protein complex. For example, the receptor protein complex can include at least one fluorescent label and can be configured to dissociate upon binding to one or more biologically active substances, thereby releasing the at least one fluorescent label into the reaction cell. Fluorescent light emitted by the fluorescent label released from the receptor protein complex upon binding can be detected to detect the state change. Alternatively, or additionally, the state change can be detectable based on light scattering, for example, by passing light through at least a portion of the reaction cell and measuring a change in the intensity of light passing through the reaction cell. Alternatively, or in addition, the state change may be detectable based on determining one or more optical properties of at least one functional surface of the reaction cell. Alternatively, or in addition, the state change of the receptor protein complex may be detected using the absorption of electromagnetic radiation in the reaction cell or at least one functional surface. For example, binding of the receptor protein complex to one or more biologically active substances may result in dissociation of one or more components of the receptor protein complex from at least one functional surface and / or dissociation of the receptor protein complex, which may result in a detectable change in the optical properties of at least one functional surface and / or a substrate contained within the reaction cell. Alternatively, or in addition, the state change may be detected based on determining the conductivity and / or a change in the conductivity of a substrate contained within the reaction cell. For this purpose, the sensor chip may include one or more electrodes disposed inside the reaction cell.Alternatively, or in addition, the state change may be detectable based on detecting an electrochemical process occurring within the reaction cell upon binding of at least a portion of the receptor protein complex to one or more biologically active substances. Alternatively, or in addition, the state change may be detectable based on determining the mass and / or change in mass of at least one functional surface of the reaction cell, e.g., determining the mass and / or change in mass of a receptor protein complex bound or immobilized on at least one functional surface of the reaction cell. For example, the receptor protein complex may be bound to at least one functional surface and dissociate therefrom upon binding to one or more biologically active substances, which may result in a measurable change in mass of the at least one functional surface or membrane. Alternatively, or in addition, a change in one or more physical or optical properties of the at least one functional surface may be detectable based on surface plasmon resonance on at least one functional surface of the reaction cell. It is emphasized that any one or more of the above-mentioned detection principles or even other detection principles may be utilized to detect a state change induced by binding of a receptor protein complex to one or more biologically active substances.

[0051] It should be noted that the sensor chip and / or the detection device may include additional technical means for actually detecting one or more of the aforementioned state changes, such as corresponding sensors or detection elements. Thus, one or both of the sensor chip and the detection device may be configured to determine the state change of at least a portion of the receptor protein complex based on optical measurements, based on detection of fluorescent light, based on fluorescence excitation of one or more components of the receptor protein complex, based on light scattering, based on determining the electrical conductivity of a substrate contained in a reaction cell of the sensor chip, based on electrochemical processes occurring in the reaction cell, based on determining one or more optical properties of at least one functional surface of the reaction cell, based on determining the absorption of electromagnetic radiation, based on determining the mass of at least one functional surface of the reaction cell, based on determining the mass of the receptor protein complex bound or immobilized on at least one functional surface of the reaction cell, and based on surface plasmon resonance on at least one functional surface of the reaction cell.

[0052] According to one embodiment, the sensor chip includes one or more connectors for operably coupling the sensor chip to a detection device, which may mean that the sensor chip can be connected to the detection device via the one or more connectors such that a change in state of at least a portion of the receptor protein complex upon binding to one or more biologically active substances is detectable.

[0053] In one embodiment, the one or more connectors can include at least one optical connector configured to couple electromagnetic radiation from a detection device to the reaction cell for optically detecting a change in the conformational state of at least a portion of the receptor protein complex upon binding to one or more biologically active agents. Alternatively, or additionally, the one or more connectors can include at least one additional optical connector for coupling electromagnetic radiation out of the reaction cell. For example, a sensor chip can include a first optical connector for transmitting electromagnetic radiation from the detection device into the sensor chip and a second optical connector for transmitting electromagnetic radiation out of the sensor chip into the detection device. The sensor chip can also include three or more optical connectors for optically coupling the sensor chip to the detection device.

[0054] The at least one optical connector and / or at least one additional optical connector, e.g., the first optical connector and the second optical connector, can include at least one opening disposed within the housing of the sensor chip, through which electromagnetic radiation can be coupled into and / or out of the sensor chip for optically detecting changes in state of the receptor-protein complex upon binding to one or more biologically active agents.

[0055] Optionally, at least one opening can be sealed with a layer of material that is translucent to electromagnetic radiation of a predetermined wavelength. For example, a state change can be detected based on fluorescence excitation of one or more fluorescent labels of the receptor-protein complex, which can be emitted upon binding to a biologically active substance. In this regard, the layer of material sealing the opening can be transparent or translucent to at least the fluorescence excitation light of a predetermined wavelength or range of wavelengths, which allows the fluorescence excitation light to couple into the reaction cell. Alternatively, or additionally, the layer of material sealing the opening can be transparent or translucent to at least the fluorescence light emitted by the fluorescent label.

[0056] The at least one opening can be shaped, oriented, or formed, for example, such that such light or electromagnetic radiation entering the reaction cell through the opening results in a sheath of light that traverses at least a portion of the reaction cell. For example, the at least one opening can be oriented parallel to the longitudinal axis of the reaction cell.

[0057] In yet another embodiment, the sensor chip further includes at least one optical guide for guiding electromagnetic radiation through the reaction cell to optically detect a state change in at least a portion of the receptor-protein complex upon binding to one or more biologically active substances. In this regard, the at least one optical guide may traverse at least a portion of the reaction cell. For example, the at least one optical guide may extend through the reaction cell parallel to a longitudinal axis of the reaction cell. Disposing one or more optical guides within the reaction cell generally may enable highly sensitive optical measurements, thereby enabling accurate and reliable detection of a state change in the receptor-protein complex upon binding.

[0058] The at least one optical guide may be aligned with and optically coupled to the at least one optical connector of the sensor chip, such that electromagnetic radiation or light may be coupled into and / or out of the at least one optical guide via the at least one optical connector.

[0059] As an example, a sensor chip can include at least two optical guides and at least one reflective element disposed at the ends of the at least two optical guides, where the at least one reflective element optically couples the at least two optical guides. In other words, electromagnetic radiation can pass through one of the optical guides, be reflected by the at least one reflective element, and be coupled to a further optical guide. Optionally, each of the at least two optical guides can be optically coupled to at least one optical connector of a sensor deceive disposed at the end of the respective optical guide opposite the at least one reflective element. In this configuration, the path length of electromagnetic radiation traversing the reaction cell through the at least two optical guides can be maximized, thereby increasing the sensitivity of the sensor chip.

[0060] In yet another embodiment, the one or more connectors on the sensor chip can include at least one electrical connector for electrically coupling the sensor chip to a detection device. The electrical connector can enable electrical signals, such as control or detection signals, to be provided by the detection device to the sensor chip, or vice versa. Alternatively, or additionally, the at least one electrical connector can enable data communication or communication coupling between the sensor chip and the detection device.

[0061] In one embodiment, the sensor chip further comprises one or more electrodes disposed at least partially within the reaction cell and configured to determine the conductivity or change in conductivity of a substrate or composition within the reaction cell. As described above, the state change induced by the binding of at least a portion of the receptor protein complex can include dissociation of the receptor protein complex into several components and / or dissociation of the receptor protein complex from at least one functional surface. Any of these state changes can result in a change in the conductivity of the substrate contained within the reaction cell, which can be measured by one or more electrodes with high accuracy, sensitivity, and performance.

[0062] In yet another embodiment, the sensor chip can further comprise at least one detection window that is translucent to electromagnetic radiation emitted and / or scattered by at least one or more components of the receptor protein complex, e.g., the at least one detection window can be translucent to fluorescent light emitted by at least one or more components of the receptor protein complex, e.g., by one or more fluorescent labels released upon binding to one or more biologically active agents.

[0063] Alternatively, or in addition, at least one detection window may be opaque to the fluorescence excitation light, thus blocking the fluorescence excitation light from leaving the reaction cell. This configuration may allow for increased sensitivity of the sensor chip, particularly when the intensity of the fluorescence excitation light is much greater than the intensity of the actual fluorescence light emitted by the fluorescent labels.

[0064] The at least one detection window may, for example, be positioned opposite the membrane, disposed towards the membrane, and / or oriented towards the membrane, such that changes in the optical properties of the membrane or functional aspects of the reaction cell can be reliably detected through the detection window of the sensor chip.

[0065] In one embodiment, the inner surface of at least one detection window facing the reaction cell can be at least partially coated with a molecular capture complex configured to bind to at least one component of a receptor protein complex, thereby capturing receptor protein complexes bound to one or more biologically active substances on the inner surface. Thus, the inner surface of the at least one detection window can act as a sink for receptor protein complexes in the reaction cell that have already bound to one or more biologically active substances. The coated inner surface allows the sensitivity of the sensor chip to be maintained at a high level even during prolonged operation in an ambient medium containing a significant amount of biologically active substances. This configuration can be particularly advantageous when detecting state changes optically, for example, based on fluorescence excitation. For example, after prolonged operation of the sensor chip or extensive exposure to biologically active substances, a large portion of the receptor protein complexes may be bound to the biologically active substances and dissociated and / or released from the membrane, which can lead to inaccurate detection of additional fluorescence induced by newly bound receptor protein complexes. Thus, the coated inner surface of the at least one detection window can ensure that already bound receptor-protein complexes or components thereof, such as one or more fluorescent labels, are trapped on the coated inner surface and cannot affect or influence the optical measurement.

[0066] To actually bind the receptor protein complex or one or more of its components to the molecular capture complex, the receptor protein complex may contain an affinity tag, preferably one that binds with high affinity to the molecular capture complex. The affinity tag may be, for example, biotin, in which case the molecular capture complex may contain streptavidin. Alternatively, or additionally, the affinity tag may be a histidine tag, in which case the molecular capture complex may contain a chelated nickel ion.

[0067] Alternatively or additionally, the inner surface of at least one detection window facing the reaction cell can be at least partially coated with a quenching molecule for quenching scattered and / or fluorescent light emitted by at least one component of the receptor protein complex, such as a fluorescent label. Alternatively or additionally, the inner surface of the membrane facing the reaction cell can be at least partially coated with a quenching molecule for quenching scattered and / or fluorescent light emitted by at least one component of the receptor protein complex. Quenching scattered and / or fluorescent light can reduce or even eliminate noise from light scattering or fluorescent emission that is not attributable to receptor protein complexes binding one or more biologically active substances.

[0068] In one embodiment, the sensor chip and / or the reaction cell may have an elongated shape, which may allow for increasing the surface area of the membrane and / or the reaction cell exposed to the surrounding medium, which may allow for improving the quality and accuracy of the actual detection of the biologically active substance, wherein the membrane may optionally be located on the longitudinal side of the sensor chip.

[0069] In yet another example, the reaction cell may have a rectangular cross section. Alternatively, or additionally, the reaction cell may be shaped as a parallelepiped. However, it should be noted that reaction cells of other geometries, shapes, or forms are also contemplated within the context of the present disclosure.

[0070] For example, the reaction cell may have a circular, elliptical, or oval cross section and / or may be tubular in shape, in which the membrane may at least partially surround the reaction cell along its periphery or perimeter, and such a configuration may allow for an increase or maximum area of the membrane through which a biologically active substance can pass and enter the reaction cell, thereby improving the accuracy and precision of detection of the biologically active substance.

[0071] In a further embodiment, the sensor chip may further include at least one reservoir fluidly connectable to the reaction cell, the at least one reservoir configured to supply deionized water to the reaction cell. Thus, the at least one reservoir may be at least partially filled with deionized water. The reservoir may also be referred to herein as a water reservoir. The reservoir may provide deionized water to the reaction cell to replenish substrate or liquid that leaks from the reaction cell over time, for example, water that passes through a membrane.

[0072] Alternatively, or additionally, the reaction cell may be dry or free of liquid, semi-solid and / or gelatinous substrates prior to first use of the sensor chip, and the sensor chip may be primed by supplying deionized water from a reservoir to the reaction cell.

[0073] In one embodiment, at least a portion of the wall of at least one reservoir may be displaceable, flexible, or movable such that the volume of the reservoir may be adjustable. Such a configuration may allow for dynamic compensation for any loss or leakage of substrate, liquid, fluid, or water from the reaction cell over time.

[0074] For example, at least a portion of at least one reservoir can be formed as a flexible bag or flexible blister, where the volume of the reservoir can be adjusted depending on the amount or volume of deionized water provided to the reaction cell, in particular without providing significant resistance to contraction even when the water is trying to leave the reservoir towards the reaction cell.

[0075] Optionally, the at least one reservoir may be surrounded by a portion of the housing of the sensor chip that includes at least one opening for pressure equalization, through which ambient medium, e.g., air, can enter the housing when water is drawn from the reservoir towards the reaction cell, e.g., by a higher osmolality in the reaction cell compared to the reservoir.

[0076] Alternatively, or additionally, the sensor chip may further include at least one movable piston configured to adjust the volume of the at least one reservoir, and the configuration may allow for dynamic compensation for any loss or leakage of substrate, liquid, fluid, or water from the reaction cell over time.

[0077] Optionally, at least one reservoir may be fluidly coupled or connected to the reaction cell by a semi-permeable membrane that blocks salt from diffusing from the reaction cell into the reservoir. The semi-permeable membrane may ensure that salt remains within the reaction cell and maintain an osmolality gradient that directs the flow of deionized water from the reservoir into the reaction cell.

[0078] In yet another embodiment, the sensor chip may further include at least one blocking element configured to block fluid communication between the reaction cell and the at least one reservoir. For example, the sensor chip may be activatable in response to unblocking the fluid communication between the reaction cell and the at least one reservoir using the at least one blocking element. In other words, the sensor chip may be activated by unblocking the fluid communication and by supplying deionized water from the reservoir into the reaction cell.

[0079] The at least one blocking element may, for example, comprise a water-impermeable membrane disposed between the at least one reservoir and the reaction cell, in which the sensor tip may be activatable in response to or by rupturing at least a portion of the water-impermeable membrane.

[0080] Alternatively, or additionally, the at least one blocking element may comprise a movable pin operable to block or unblock fluid communication between the reaction cell and the at least one reservoir, wherein the sensor tip may be actuable in response to moving the movable pin such that fluid communication between the reaction cell and the at least one reservoir is unblocked or established.

[0081] According to one embodiment, the receptor protein complexes can each include at least one ligand-binding domain of a receptor protein configured to bind to one or more biologically active substances and to undergo a conformational change upon binding to one of the biologically active substances. Optionally, at least some of the receptor protein complexes can include multiple ligand-binding domains of one or more receptor proteins. Thus, multiple biologically active substances can be bound by a single receptor protein complex, improving the overall sensitivity of the sensor chip.

[0082] Further optionally, the multiple ligand-binding domains may be of different types and configured to bind different types of bioactive substances. In other words, a receptor protein complex may include at least portions, e.g., ligand-binding domains, of different types of receptor proteins configured to bind different types of bioactive substances. Thus, multiple different types of bioactive substances may be detected by a single receptor protein complex.

[0083] According to one embodiment, at least a portion of the receptor protein complex may comprise at least one ligand-binding domain of a receptor protein that is a xenosensor protein or a hormone receptor protein. Alternatively, or in addition, the receptor protein complexes may each comprise at least one ligand-binding domain of a receptor protein selected from the group consisting of the aryl hydrocarbon receptor, the constitutive androstane receptor, the pregnane X receptor, and the estrogen receptor.

[0084] Alternatively, or in addition, at least a portion of the receptor protein complex may comprise at least one binding domain of an aryl hydrocarbon receptor or aryl hydrocarbon receptor protein. For example, at least a portion of the receptor protein complex may comprise at least a PAS (Per-ARNT-Sim) domain or the entire aryl hydrocarbon receptor protein, which may enable detection of materials, compounds, molecules, and / or agents, such as halogenated aromatic hydrocarbons, e.g., polychlorinated dibenzodioxins, dibenzofurans, and biphenyls, and / or polycyclic aromatic hydrocarbons, e.g., 3-ethylcholanthrene, benzo[a]pyrene, benzanthracene, and benzoflavone.

[0085] Generally, at least a portion of the receptor protein complex can comprise recombinant or non-recombinant protein. Alternatively, or additionally, the receptor protein complex can comprise at least a portion of a monomeric receptor protein, a homodimeric receptor protein complex, or a heterodimeric receptor protein complex, respectively.

[0086] Additionally, at least a portion of the receptor protein complexes can include organic or inorganic moieties that dissociate from the remainder of the respective receptor protein complex upon binding to one or more biologically active agents.

[0087] As an example, a receptor protein complex may contain at least one fluorescent label that dissociates or is released from the remainder of the respective receptor protein complex upon binding to one or more biologically active substances. Using such receptor protein complexes, a state change induced by binding of the receptor protein complex to one or more biologically active substances can be detected based on fluorescence excitation of the at least one fluorescent label that dissociates or is released from the remainder of the receptor protein complex. Optionally, at least a portion of the receptor protein complex may contain multiple fluorescent labels of the same or different types. As an example, the at least one fluorescent label may be a fluorescent dye or green fluorescent protein.

[0088] Alternatively, or in addition, the receptor protein complexes may include nanoparticles that dissociate or are released from the remainder of the respective receptor protein complex upon binding to one or more biologically active substances. The use of nanoparticles, e.g., gold nanoparticles, as the moieties released upon binding can increase the change in mass induced by the binding event, thereby improving the sensitivity and accuracy of detection of biologically active substances.

[0089] In yet another embodiment, the sensor chip further comprises a chip identifier for identifying the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip. Similarly, the chip identifier may enable identification of the type of bioactive substance detectable by the sensor chip. In one embodiment, the chip identifier may comprise information or data indicative of the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip.

[0090] Optionally, the chip identifier may be readable by a user device and / or by a detection device. As used herein, a user device may refer to any device that can be operatively and / or communicatively coupled to a sensor chip or a detection device, such as, for example, a smartphone, tablet, personal computer, laptop, smart device, smartwatch, or any other computing device. Reading the chip identifier may make it possible to provide the user device and / or detection device with information related to, among other things, the sensor chip and / or the type of receptor-protein complex. This may further make it possible to ensure proper operation and control of the sensor chip by the detection device when the sensor chip is inserted into the detection device.

[0091] In one embodiment, the chip identifier may include one or more of a barcode, a QR code, an RFID tag, a label, and a data storage. The barcode, QR code, label, or RFID tag may be read by the user device and / or the detection device based on optical detection or using an RFID reader employed in the user device and / or the detection device. Similarly, data stored in the data storage may be read by the user device and / or the detection device based on establishing data communication, for example, via one or more connectors on the sensor chip.

[0092] In yet another embodiment, the sensor chip may further include a data storage configured to store historical data indicative of the usage or remaining life of the sensor chip, and the data may be read by a user device and / or a detection device. Storing the historical data in the data storage may, in particular, enable the sensor chip to be reused, e.g., by reinserting it into a detection device, while still ensuring proper functionality of the sensor chip, since, e.g., the detection device may determine that the life of the sensor chip is still valid.

[0093] For example, one or more operating parameters associated with the use of the sensor chip may be measured over the life or lifetime of the chip and stored in the data storage as historical data, i.e., the data storage may be configured to store one or more operating parameters indicative of the usage or remaining life of the sensor chip.

[0094] Optionally, a notification may be provided by the detection device and / or user device if the remaining life of the sensor chip reaches or falls below a predetermined threshold, for example due to depletion of receptor protein complexes in the reaction cell, thereby indicating that the sensor chip should be replaced. Optionally, the detection device and / or user device may determine the depletion of receptor protein complexes in the reaction cell based on historical data, and determine the remaining life of the sensor chip based on the determined depletion.

[0095] Alternatively, or additionally, the detection device and / or user device may determine cumulative exposure to a biologically active agent, e.g., cumulative air pollution, based on historical data. Optionally, this information may be provided to the user, e.g., at a user interface of the detection device and / or user device.

[0096] In one example, the data storage of the sensor chip may be accessible by the detection device upon operably coupling the sensor chip to the detection device, e.g., upon at least partially inserting the sensor chip into the detection device. Alternatively, or additionally, the data storage of the sensor chip may be readable by the detection device upon operably coupling the sensor chip to the detection device. For example, the data storage and / or chip identifier of the sensor chip may be automatically detected and / or read upon operably coupling the sensor chip to the detection device.

[0097] Generally, the sensor chip may include multiple reaction cells and / or membranes. Optionally, the multiple reaction cells may contain different types of receptor protein complexes configured to bind to different types of bioactive substances. These configurations may improve the sensitivity of the sensor chip and enable a wider range of bioactive substances that can be detected by the sensor chip. Therefore, a compact sensor chip may be provided that may enable the detection of multiple different bioactive substances with high accuracy.

[0098] In yet another embodiment, the sensor chip further includes one or more sensors configured to determine a change in state of at least a portion of the receptor protein complex. Optionally, the sensor chip may include processing circuitry configured to provide a detection signal indicative of the determined change in state of at least a portion of the receptor protein complex. Thus, the electronics and sensing elements for the actual detection of the change in state of the receptor protein complex may be at least partially or completely contained within the sensor chip. However, alternatively or additionally, at least a portion of the one or more sensors and / or processing may be located within the sensing device.

[0099] For example, the sensor chip may include one or more optical sensors, such as photodetectors, for optically detecting state changes. Alternatively, or additionally, the sensor chip may include one or more electrodes for detecting state changes based on conductivity measurements within the reaction cell. Alternatively, or additionally, the sensor chip may include one or more piezoelectric elements positioned and configured to detect state changes based on determining the mass and / or change in mass of a receptor protein complex immobilized on and / or released from at least one functional surface of the sensor chip. Alternatively, the one or more piezoelectric elements may be positioned and configured to determine the mass and / or change in mass of a receptor protein complex immobilized on and / or released from at least one functional surface of the sensor chip based on determining the mass and / or change in mass of the receptor protein complex or one or more components thereof on one or more inner surfaces of a reaction cell disposed toward the at least one functional surface.

[0100] A further aspect of the present disclosure relates to the use of the sensor chip described hereinabove and below for detecting one or more biologically active substances. Any disclosure provided hereinabove and below with reference to the sensor chip applies equally to the use of the sensor chip.

[0101] In a further aspect of the present disclosure, a detection device for detecting one or more biologically active substances in a surrounding medium is provided. The detection device comprises a housing configured to at least partially receive at least one sensor chip and operably couple the detection device to the at least one sensor chip, as described hereinabove and below. The detection device further comprises processing circuitry configured to provide a detection signal indicative of the presence of one or more biologically active substances in the surrounding medium based on determining a state change of at least a portion of a receptor protein complex in a reaction cell of the at least one sensor chip, the state change being induced by binding of the one or more receptor protein complexes with the one or more biologically active substances that pass from the surrounding medium through a membrane of the sensor chip into the reaction cell of the sensor chip.

[0102] It should be noted that the detection device may optionally include one or more sensors that determine a change in state of at least a portion of the receptor-protein complex within the reaction cells of at least one sensor chip. Alternatively, at least some or all of the sensors may be included within the sensor chip. Similarly, at least some or all of the processing circuitry may be located within or included within the sensor chip.

[0103] The processing circuit may include, for example, one or more processors, one or more controllers, or one or more microcontrollers for data processing or operational control of the detection device and / or sensor chip. Optionally, at least a portion of the processing circuit may be implemented on a printed circuit board. Alternatively, or additionally, at least a portion of the processing circuit may be implemented as a smart chip or smart device. Alternatively, or additionally, at least a portion of the processing circuit may be implemented as an application-specific integrated circuit (ASIC).

[0104] In yet a further aspect of the present disclosure, there is provided a detection device operably coupled to at least one sensor chip as described hereinabove and below for detecting one or more biologically active substances in a surrounding medium. The detection device comprises at least one sensor configured to determine a change in state of at least a portion of a receptor protein complex in a reaction cell of the at least one sensor chip, the change in state being induced by binding of the one or more receptor protein complexes with one or more biologically active substances that pass from the surrounding medium through a membrane of the sensor chip into the reaction cell of the sensor chip. The detection device further comprises a processing circuit coupled to the at least one sensor, the processing circuit configured to provide a detection signal indicative of the presence of the one or more biologically active substances in the surrounding medium based on determining the change in state of at least a portion of the receptor protein complex.

[0105] In one example, the ambient medium may include ambient air. Alternatively, or additionally, the detection device may be or be configured as an environmental monitor for monitoring the quality of ambient air.

[0106] The detection device can be or can be configured as a stationary and / or desktop device. The detection device can be utilized, for example, in a home or office to monitor the air quality in that environment. Alternatively, the detection device can be at least temporarily installed elsewhere, such as in a vehicle or the like. Generally, the detection device can be configured to monitor air quality continuously or at predetermined time intervals.

[0107] Alternatively, the detection device may be or be configured as a portable, mobile, and / or handheld device that can be carried by a person to monitor the air quality around them, for example, continuously or at predetermined time intervals. The detection device may be carried, for example, in a pocket, bag, backpack, or handbag, or may be attached to an item of the person, such as clothing, a bag, backpack, or handbag.

[0108] As used herein, a detection signal may refer to or indicate an electronically processable signal, such as, for example, an electronic signal or a data signal. Optionally, the detection signal can be used by processing circuitry to provide a readout indicative of one or more biologically active substances detected, for example, at a user interface of the detection device. Alternatively, or additionally, the detection signal can be transmitted from the detection device to a user device and further processed by the user device to provide a readout indicative of one or more biologically active substances detected.

[0109] The detection signal may be indicative of the amount of one or more biologically active substances per volume of the surrounding medium, the mass of the biologically active substances per volume of the surrounding medium, the concentration of the biologically active substances in the surrounding medium, the ability of the surrounding medium to activate a receptor protein, and the biological activity of the surrounding medium, and thus one or more of the foregoing quantities may be determined by a processing circuit and / or a user device based on processing of the detection signal.

[0110] In one embodiment, the detection device may be mechanically couplable to the sensor chip. The mechanical coupling may include, for example, a snap-fit connection, surface features that at least partially engage the sensor chip and the detection device, mechanically fastening the sensor chip to the detection device, for example, by screw fastening, or other mechanical coupling. Mechanically coupling the sensor chip to the detection device may ensure that the sensor chip is in a predetermined position and / or orientation that enables operative coupling between the detection device and the sensor chip. Thus, mechanically coupling the sensor chip to the detection device may optionally include establishing an operative coupling between the sensor chip and the detection device, which may include, for example, establishing one or more optical connections, one or more electrical connections, and / or one or more data connections. Thus, mechanically coupling the sensor chip to the detection device may ensure that the sensor chip is functional and operational.

[0111] Alternatively, or additionally, the detection device may be magnetically couplable to the sensor chip. For example, the detection device may include one or more magnets that interact with one or more magnetic counter components or magnetic elements of the sensor chip to magnetically couple the sensor chip to the detection device. Magnetically coupling the sensor chip to the detection device may also ensure that the sensor chip is in a predetermined position and / or orientation that allows for operative coupling between the detection device and the sensor chip. Thus, magnetically coupling the sensor chip to the detection device may optionally include establishing an operative coupling between the sensor chip and the detection device, which may include, for example, establishing one or more optical connections, one or more electrical connections, and / or one or more data connections. Thus, magnetically coupling the sensor chip to the detection device may ensure that the sensor chip is functional and operative.

[0112] In one embodiment, the detection device may be configured to at least partially receive the at least one sensor chip. For example, the detection device may include at least one socket configured to at least partially receive the at least one sensor chip. The sensor chip may be at least partially removably inserted into the detection device or the at least one socket. Alternatively, or additionally, the at least one socket may be configured to at least partially receive the at least one sensor chip such that a housing of the detection device at least partially surrounds the at least one sensor chip. Inserting the sensor chip at least partially into the detection device or socket may protect the sensor chip and ensure that an operable connection between the sensor chip and the detection device can be established.

[0113] Optionally, the at least one socket may include at least one surface feature that is complementary to at least one surface feature of the sensor chip to ensure correct positioning of the sensor chip within the at least one socket. For example, the at least one surface feature of the at least one socket may include one or more guides for positioning the sensor chip within the socket. Alternatively, or additionally, the at least one surface feature of the at least one socket may be configured to at least partially engage with at least one surface feature of the sensor chip such that the sensor chip is removably securable within the socket. Thus, the surface feature of the socket and the surface feature of the housing of the sensor chip may optionally provide a click-fit or snap-fit mechanism for securing the sensor chip within the socket.

[0114] It should be noted that a sensing device may include multiple sockets configured to receive multiple sensor chips of the same or different types. For example, different types of sensor chips for detecting different types of bioactive substances or one or more environmental parameters, such as UV radiation exposure or ozone exposure, may be utilized in a single sensing device. Thus, the sensing device may be used to comprehensively monitor an environment.

[0115] The processing circuitry of the detection device may be configured to determine the presence of one or more biologically active substances in the surrounding medium based on detecting, using the sensor chip or at least one sensor of the detection device, a change in position of one or more receptor proteins in the reaction cell upon binding to one or more biologically active substances.

[0116] For example, the detection device may be configured to determine one or more of the presence, number, mass, density, and mass density of receptor protein complexes dissolved in the substrate of the reaction cell of at least one sensor chip. Alternatively, or additionally, the detection device may be configured to determine one or more of the presence, number, mass, density, and mass density of receptor protein complexes dissolved in the substrate of the reaction cell of at least one sensor chip based on determining a change in at least one of the optical signal and the electrical signal transmitted to the sensor chip. Thus, the detection device may be configured to detect a state change induced by binding of at least a portion of the receptor protein complexes to one or more biologically active substances based on determining a change in at least one of the optical signal and the electrical signal transmitted to the sensor chip.

[0117] In one embodiment, the receptor protein complexes can be configured to dissociate from at least one functional surface of the reaction cell upon binding to one of the biologically active substances, and the detection device can be configured to determine one or more of the number, mass, density, and mass density of the receptor protein complexes immobilized on or released from the at least one functional surface of the reaction cell.

[0118] Optionally, the detection device may include one or more piezoelectric elements configured to detect one or more biologically active substances in the surrounding medium by determining the mass and / or mass change of a receptor-protein complex immobilized on or released from at least one functional surface of the reaction cell. In one embodiment, the one or more piezoelectric elements of the detection device may be positioned adjacent to, in close proximity to, or in contact with a component of the sensor chip carrying at least one functional surface, such as a membrane or a portion of the sensor chip housing disposed toward or facing the membrane. The mass and / or mass change may be determined based on exciting mechanical vibrations of the component of the sensor chip carrying at least one functional surface, such as a membrane, and measuring characteristics of the mechanical vibrations, such as damping behavior. This may enable, for example, a processing circuit of the detection device to determine the mechanical properties of the component of the sensor chip carrying at least one functional surface, and thereby determine the mass and / or mass change of a receptor-protein complex immobilized on or released from at least one functional surface of the reaction cell. However, it should be noted that one or more piezoelectric elements may alternatively be located within the sensor chip and operatively controlled by the sensing device.

[0119] Alternatively, or in addition, the one or more piezoelectric elements may be configured to determine the mass and / or mass change of a receptor protein complex immobilized on or released from at least one functional surface of the reaction cell based on determining the mass of one or more components of the receptor protein complex bound to an inner surface of the reaction cell disposed toward or facing the at least one functional surface of the reaction cell. For example, upon binding, the receptor protein complex may be released from the at least one functional surface and diffuse toward the inner surface of the reaction cell disposed toward the at least one functional surface. The receptor protein complex or its components may accumulate on the inner surface, and this accumulation can be measured by determining the mass and / or mass change of the receptor protein complex on the inner surface. In this configuration, the one or more piezoelectric elements of the detection device may be positioned adjacent to, close to, or in contact with a sensor chip or a component of the reaction cell that carries the inner surface of the reaction cell. The mass and / or mass change may be determined, for example, by exciting mechanical vibrations of a component of the sensor chip, as described herein above.

[0120] In one embodiment, one or more piezoelectric elements can be mechanically coupled to one or more functional surfaces of a reaction cell of a sensor chip. Alternatively, or additionally, one or more piezoelectric elements can be mechanically coupled to one or more inner surfaces of a reaction cell of a sensor chip that are disposed toward one or more functional surfaces of the reaction cell. By mechanically coupling a piezoelectric element to at least one functional surface or one or more inner surfaces of a reaction cell, the mass and / or change in mass of a receptor-protein complex immobilized on or released from the at least one functional surface can be reliably detected with high precision. As described above, one or more piezoelectric elements can be positioned, for example, adjacent to a component that supports or supports at least one functional surface or one or more inner surfaces of a reaction cell. For example, if at least one functional surface is provided or defined on an inner surface of a membrane, one or more piezoelectric elements can be positioned on or in contact with the opposite side of the membrane.

[0121] In one embodiment, the receptor protein complexes may include at least one fluorescent label, and the detection device may be configured to detect one or more biologically active substances based on exciting the one or more fluorescent labels and detecting fluorescent light emitted by the one or more fluorescent labels. For example, the receptor protein complexes may include at least one fluorescent label that dissociates from the remainder of the respective receptor protein complexes upon binding to one or more of the biologically active substances, and the detection device may be configured to detect the one or more biologically active substances based on exciting the one or more fluorescent labels dissociated from the one or more receptor protein complexes and detecting fluorescent light emitted by the one or more dissociated fluorescent labels. Thus, the detection device may be configured to detect a state change induced by the binding of the receptor protein complexes to one or more biologically active substances based on fluorescent excitation of free fluorescent labels or light-absorbing labels in the reaction cell that are released from the receptor protein complex upon binding.

[0122] The detection device may include one or more light sources, such as laser diodes or light emitting diodes (LEDs), configured to excite the one or more fluorescent labels, and the detection device may include one or more photodetectors configured to detect fluorescent light emitted by the one or more fluorescent labels.

[0123] Alternatively, or additionally, the detection device may include one or more light sources configured to illuminate at least a portion of the reaction cell, and the detection device may include one or more light detectors configured to detect light scattered by one or more components of the receptor protein complex in the reaction cell. Thus, the detection device may be configured to detect a state change based on detection of scattered light and / or based on light scattering.

[0124] In one embodiment, one or more photodetectors can be positioned adjacent to or near a detector socket for at least partially receiving the sensor chip to detect electromagnetic radiation transmitted out of the reaction cell. For example, one or more light sources can be positioned adjacent to or near a detector socket for at least partially receiving the sensor chip such that electromagnetic radiation emitted by the one or more light sources can be coupled into the reaction cell.

[0125] Alternatively, or additionally, one or more photodetectors may be positioned opposite a detection window of the sensor chip, in other words, one or more photodetectors may be positioned opposite at least one detection window of the sensor chip when the sensor chip is at least received by the detection device.

[0126] In one embodiment, one or more light sources may be positioned to couple electromagnetic radiation or light into the reaction cell through one or more optical connectors on the sensor chip.

[0127] Alternatively, or additionally, the detection device may include one or more light sources arranged to couple electromagnetic radiation into one or more optical guides that traverse at least a portion of the reaction cell of the sensor chip, and the detection device may include one or more photodetectors configured to detect the electromagnetic radiation traversing the one or more optical guides. In one embodiment, the one or more light sources may be arranged to be aligned with ends of the one or more optical guides. Alternatively, or additionally, the one or more photodetectors may be arranged to be aligned with ends of the one or more optical guides. Such a configuration may enable reliable optical measurement or detection of a change in state of a receptor-protein complex with accuracy, sensitivity, and precision.

[0128] In one embodiment, the processing circuitry can be configured to determine one or more optical properties of at least one of a functional surface and an interior surface of a reaction cell disposed adjacent to the one or more optical guides. For example, the processing circuitry can be configured to determine the one or more optical properties based on determining absorption of evanescent light transmitted into the reaction cell through the one or more optical guides. Furthermore, measuring the optical properties of the functional surface or the interior surface of the reaction cell disposed adjacent to the at least one optical guide can enable reliable optical measurement or detection of changes in state of receptor-protein complexes with high accuracy, sensitivity, and precision.

[0129] In still further embodiments, the detection device may further include a housing configured to at least partially surround the sensor chip, the housing including one or more holes to allow the surrounding medium to pass through, thereby enabling at least a portion of the sensor chip to contact the surrounding medium. By providing one or more holes in the housing, it may be ensured that the membrane of the sensor chip can contact the surrounding medium, thereby ensuring that the biologically active substance can enter the reaction cell from the surrounding medium and be detected therein.

[0130] Optionally, the detection device may further include one or more channels for passing the surrounding medium through one or more holes in the housing of the detection device to at least a portion of the sensor chip, in other words, one or more holes disposed in the housing of the detection device may be fluidly coupled via one or more channels, thereby allowing the surrounding medium to be delivered to the sensor chip or at least a portion thereof through the holes and channels.

[0131] Optionally, the detection device may further include one or more ventilation devices disposed in one or more channels and configured to deliver or transport ambient medium to at least a portion of the sensor chip through one or more holes in the housing of the detection device. For example, one or more micro-ventilators may be disposed in one or more channels. Such a configuration may prevent ambient medium from stagnating and may ensure that the sensor chip, or at least a portion thereof, can come into contact with ambient medium currently present around the detection device.

[0132] In still further embodiments, the detection device may include one or more heating elements configured to heat at least a portion of the sensor chip. The one or more heating elements may ensure that the sensor chip, the reaction cell, or at least a portion thereof can be maintained at or near the predetermined operating temperature of the sensor chip, e.g., at or near body temperature or room temperature. For example, some mechanisms and detection principles applied may involve diffusion processes, such as the diffusion of a biologically active substance into the reaction cell and the diffusion of one or more components of a receptor protein complex through the reaction cell. Such processes are generally temperature-dependent, and maintaining a minimum temperature may be necessary to obtain a detection signal within a reasonable time. Furthermore, state changes of the receptor protein complex may be temperature-dependent and may be better observable at, near, or above the predetermined operating temperature of the sensor chip. Placing a heating element in the detection device may be particularly advantageous in low-temperature regions or cold weather because proper functioning of the sensor chip and the detection device can be ensured by heating the sensor chip.

[0133] For example, one or more heating elements can be positioned adjacent to a socket of the detection device to at least partially receive the sensor tip, such that the sensor tip, or at least a portion thereof, can be efficiently heated by the one or more heating elements.

[0134] Optionally, the detection device may further include one or more temperature sensors configured to determine the temperature of at least a portion of the sensor chip, which may provide comprehensive temperature control in the detection device to ensure that the sensor chip, the reaction cell, or at least a portion thereof, can be maintained at or near a predetermined operating temperature of the sensor chip.

[0135] In one embodiment, the processing circuitry can be configured to control the temperature of at least a portion of the sensor chip based on determining the temperature of at least a portion of the sensor chip using one or more temperature sensors. For example, the processing circuitry can be configured to control the temperature of at least a portion of the sensor chip such that the reaction cell, or at least a portion thereof, can be maintained at or near a predetermined operating temperature of the sensor chip. Optionally, the predetermined operating temperature can be stored in data storage in the detection device and / or sensor chip so that it can be accessed by the processing circuitry to control the temperature during operation.

[0136] In a further embodiment, the detection device further comprises one or more electrical connectors for connecting to the one or more electrical connectors on the sensor chip upon insertion of the sensor chip into the detection device, preferably such that the electrical connection between the sensor chip and the detection device can be established automatically upon insertion of the sensor chip into the detection device.

[0137] In one embodiment, a processing circuit can be coupled to one or more electrodes of the sensor chip, and the processing circuit can be configured to determine the conductivity of a substrate or composition within the reaction cell. Thus, the processing circuit can be configured to control one or more electrodes, e.g., by applying a voltage and / or current to the one or more electrodes, to perform a conductivity measurement within the reaction cell to detect a state change induced by binding of the receptor protein complex to one or more biologically active agents.

[0138] Alternatively or additionally, the processing circuit may be configured to determine one or more operating parameters indicative of the sensor chip's usage or remaining life. Alternatively or additionally, the processing circuit may be configured to determine at least the sensor chip's usage or remaining life based on determining one or more operating parameters of the sensor chip. As described above, the sensor chip may have a limited life due to, for example, depletion of the receptor protein complex. By determining the sensor chip's remaining life or usage, a user can be notified, for example, when the sensor chip needs to be replaced. Additionally, the sensor chip can be used multiple times, e.g., reinserted into a detection device while ensuring that the sensor chip is still operational or functional.

[0139] In one embodiment, the processing circuitry may be configured to determine the usage or remaining life of at least one sensor chip based on retrieving historical data indicative of the usage or remaining life of the sensor chip from the sensor chip's data storage. Thus, the historical data may be stored on the sensor chip and processed by the detection device's processing circuitry to determine the usage or remaining life of the sensor chip. The historical data may include, for example, values of one or more operating parameters accumulated over the current or past operating time of the sensor chip.

[0140] For example, the processing circuitry may be configured to determine the usage or remaining life of at least one sensor chip based on comparing at least a portion of the determined one or more operating parameters of the sensor chip and / or historical data retrieved from data storage of the sensor chip to one or more thresholds, which may be stored in data storage of the detection device or retrieved by the processing circuitry from data storage of the sensor chip.

[0141] Optionally, the processing circuitry may be configured to determine the usage or remaining life of at least one sensor chip based on determining the type of sensor chip and / or the type of receptor protein complex used on the sensor chip, where the type of sensor chip and / or receptor protein complex used may be determined based on a reading of a chip identifier of the sensor chip, based on retrieving corresponding data from a data storage of the sensor chip, and / or based on user input, for example via a user interface of the detection device.

[0142] Additionally, the processing circuitry may optionally be configured to store one or more operating parameters in the detection device data storage and / or the sensor chip data storage, such that the one or more operating parameters may be stored, for example as historical data, which allows for the determination of the usage and / or remaining life of the sensor chip at a later point in time.

[0143] In one embodiment, the processing circuit can be configured to determine one or more operating parameters based on monitoring the temperature of at least a portion of the sensor chip. In other words, the one or more operating parameters can include the temperature of at least a portion of the sensor chip, such as the temperature over time. Because certain processes or reactions within the reaction cell, such as the diffusion as well as depletion of receptor-protein complexes, can be temperature-dependent, the temperature of at least a portion of the sensor chip over time can allow for an accurate determination of the usage and / or remaining life of the sensor chip.

[0144] Alternatively, or additionally, the processing circuitry may be configured to determine depletion of receptor protein complexes in the sensor chip over time. For example, the processing circuitry may be configured to determine depletion of receptor protein complexes based on one or more operating parameters of the sensor chip and / or detection device over time, such as the temperature of at least a portion of the sensor chip over time. Optionally, the processing circuitry may be configured to determine the remaining lifetime of the sensor chip based on the determined depletion of receptor protein complexes in the sensor chip over time.

[0145] In a further embodiment, the detection device may include a user interface, and the processing circuitry may be configured to notify a user via the user interface upon expiration of the sensor chip's lifespan, so that the user can be notified upon expiration of the sensor chip's lifespan so that they can replace the sensor chip in a timely manner.

[0146] Optionally, the processing circuitry may be configured to provide information related to the determined one or more biologically active substances to a user via a user interface. For example, information regarding the immediate or current quality of the surrounding medium, e.g., air quality, and / or immediate exposure to a biologically active substance may be provided in the user interface. Other information, such as past exposure, or other information related to the operation of the sensor chip and / or detection device, e.g., information regarding the usage and / or remaining life of the sensor chip, may also be provided in the user interface.

[0147] Further optionally, the processing circuitry may be configured to notify the user via the user interface when it determines that the concentration of the biologically active substance in the surrounding medium has reached or exceeded a predetermined threshold, thus providing a warning to the user when a high concentration of the biologically active substance is detected.

[0148] In general, the user interface may be any type of user interface, for example, the user interface may include one or more of a vibrating element, a display, one or more LEDs, and a speaker.

[0149] In yet another embodiment, the sensor chip may include a chip identifier for identifying the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip, and the processing circuit may be configured to obtain information or data indicative of the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip from the chip identifier. The detection device may optionally include one or more of a barcode reader, a QR code reader, and an RFID scanner or reader for this purpose.

[0150] The detection device may further include one or more energy storage units for supplying electrical energy. For example, the detection device may include one or more batteries, accumulators, and / or capacitors for supplying electrical energy to the detection device and / or the sensor chip. Such a configuration may be particularly advantageous when the detection device is designed as a portable or mobile device. However, alternatively or additionally, the detection device may also be powered via a supply grid.

[0151] The detection device may further include communication circuitry for communicatively coupling the detection device with a user device. For example, the communication circuitry may include wireless communication circuitry, preferably a Bluetooth transmitter, an infrared transmitter, or a wireless LAN transmitter. This may enable wireless data connection and communication between the detection device and the user device. In particular, this may enable the user device to acquire data from the detection device, such as data indicative of exposure to a biologically active agent and / or data indicative of the quality of the surrounding medium. The data may then be further processed and / or displayed on the user device and can be evaluated by a user.

[0152] In another embodiment, the detection device may further include one or more radiation sensors that measure the exposure of the detection device to ionizing radiation. For example, the one or more radiation sensors may include at least one of a reversible photochromic layer sensitive to UV radiation and a radiochromic dye film sensitive to ionizing radiation. The use of one or more radiation sensors may enable the determination of exposure to radiation in parallel or simultaneously with the determination of the bioactive substance. Thus, the quality of the surrounding medium and / or the user's exposure to various environmental parameters may be comprehensively assessed.

[0153] Alternatively, or in addition, the detection device may further include one or more of a humidity sensor, a volatile organic carbon sensor, an ozone sensor, a particulate matter sensor, a nitric acid sensor, and a carbon monoxide sensor, and the use of one or more of the foregoing sensors may enable a comprehensive determination or assessment of a user's exposure to various other environmental parameters in addition to exposure to biologically active agents.

[0154] According to a further aspect of the present disclosure, there is provided a detection system for detecting one or more biologically active substances in a surrounding medium. The detection system comprises at least one sensor chip as described hereinabove and below, and a detection device as described hereinabove and below. Any disclosure provided above and below with reference to either the detection device or the sensor chip applies equally to the detection system.

[0155] Further aspects of the present disclosure relate to the use of a detection device, as described hereinabove and below, and a detection system, as described hereinabove and below, for detecting one or more biologically active substances in a surrounding medium.

[0156] According to a further aspect of the present disclosure, there is provided a method of detecting one or more biologically active substances in a surrounding medium by or using one or more of the detection system, detection device, and sensor chip as described hereinabove and below. Alternatively, or additionally, the method may relate to a method of operating one or more of the detection system, detection device, and sensor chip. The method comprises: - passing one or more biologically active substances through a membrane of the sensor chip into a reaction cell of the sensor chip, for example by diffusion; - binding one or more biologically active substances to one or more receptor protein complexes, thereby inducing a change in state of at least a portion of the receptor protein complexes; - detecting the induced change in state of at least a portion of the receptor protein complex with a detection device, sensor chip and / or detection system; - generating, by a detection device, sensor chip and / or detection system, a detection signal indicative of the presence of one or more biologically active substances in the surrounding medium based on the determined change in state of at least a portion of the receptor-protein complex.

[0157] It is again emphasized that all disclosures presented hereinabove and below relating to any of the detection devices, sensor chips, and detection systems apply equally to methods of detecting one or more biologically active substances.

[0158] In one embodiment, passing one or more biologically active substances through the membrane of the sensor chip includes contacting the membrane of the sensor chip with the surrounding medium.

[0159] Optionally, the method may further include activating the sensor chip based on supplying deionized water from a reservoir of the sensor chip to a reaction cell of the sensor chip.

[0160] For example, activating the sensor chip can include unblocking fluid communication between the at least one reservoir and the reaction cell using or upon activating at least one blocking element between the at least one reservoir and the reaction cell of the sensor chip. Optionally, the at least one blocking element can include a movable pin disposed between the reservoir and the reaction cell, and activating the sensor chip can include moving the movable pin.

[0161] Alternatively, or additionally, the at least one blocking element may include a water-impermeable membrane disposed between the reservoir and the reaction cell, and activating the sensor chip may include disrupting at least a portion of the water-impermeable membrane.

[0162] Alternatively, or additionally, activating the sensor chip may include removing a sealing cover from the outer surface of the membrane, which may establish contact between the membrane and the surrounding medium, thereby allowing the biologically active substance to be detected to pass through the membrane and into the reaction cell.

[0163] In yet another embodiment, detecting the induced state change can include determining one or more of the number, mass, density, and mass density of receptor protein complexes dissolved in a substrate of at least one reaction cell of the sensor chip. Alternatively, or additionally, detecting the induced state change can include determining one or more of the number, mass, density, and mass density of receptor protein complexes immobilized on or released from at least one functional surface of the reaction cell.

[0164] Alternatively or additionally, detecting the induced state may include determining one or more of the number, mass, density, and mass density of receptor protein complexes immobilized on or released from at least one inner surface of the reaction cell disposed toward at least one functional surface of the reaction cell. Alternatively or additionally, detecting the induced state change may include exciting one or more fluorescent labels of the receptor protein complexes and detecting fluorescent light emitted by the one or more fluorescent labels. Alternatively or additionally, detecting the induced state change may include detecting light scattered by one or more components of the receptor protein complex in the reaction cell. Alternatively or additionally, detecting the induced state change may include determining one or more optical properties of at least one of the functional surface and the inner surface of the reaction cell. Alternatively or additionally, detecting the induced state change may include determining absorption of evanescent light transmitted into the reaction cell through one or more optical guides of the sensor chip.

[0165] Below are summarized various aspects, examples, and exemplary embodiments of the present disclosure, which should be construed as non-limiting and serve merely for illustrative purposes.

[0166] The sensor chips, detection devices, and detection systems described herein can employ receptor protein complexes, such as biological receptor proteins, as detection or chemical recognition elements. The receptor protein complexes can exist in an aqueous environment, for example, within the reaction cell of the sensor chip, and can interact with the surrounding medium through, for example, a porous membrane with low diffusion resistance. The receptor protein complexes can be or include, for example, heterologous sensor proteins or hormone receptors, such as AHR, CAR, PXR, and ER. This list of candidate receptor protein complexes is not exhaustive; any other protein exhibiting binding specificity for one or several ligand molecules can function as a chemical recognition element.

[0167] The present disclosure may not be limited to personalized air quality monitoring, but may also be applied to detecting contaminants in, for example, water or soil extracts. Furthermore, proteins active in homeostatic biochemical processes, for example metabolism, may be used, in which case the detection system may be used for diagnostic applications.

[0168] Furthermore, gene sequences that can be used for cloning receptor protein complexes can be of human, animal, plant, fungal, bacterial, or classical origin. For example, depending on the operating principle of the sensor chip at the molecular level, they can be used in non-recombinant or recombinant protein form. Furthermore, combinations of non-recombinant and recombinant proteins, and combinations of different proteins of the same or different species origin, can be used as at least part of the receptor protein complex. Optionally, the receptor protein complex can be chemically labeled after its isolation, for example, with a fluorophore. As used herein, candidate proteins, regardless of their biological origin, whether recombinant or non-recombinant, and whether labeled or unlabeled, are collectively referred to as receptor protein complexes. Furthermore, proteins that can interact in some way with the receptor protein complex in living cells but are not receptor proteins themselves can be included. The additional proteins can be of any origin, recombinant or non-recombinant, and can be labeled or unlabeled.

[0169] As described above, the detection system can be a stationary device or a portable device, e.g., for environmental monitoring. The detection system can have one or more of the features described below. The detection system can include one or more replaceable and / or disposable sensor chips that can be attached to the detection device, e.g., by a click mechanism or magnetic connection. The sensor chip can contain the receptor protein in a suitable liquid, semi-solid, and / or gelatinous matrix. The sensor chip can provide suitable electrical and / or optical contacts for connecting the sensor chip to the detection device. The sensor chip can provide a gas-permeable surface through which mass transfer occurs from the surrounding medium or atmosphere to the reaction cell. Optionally, the chip can contain some or most of the transducer and / or processing circuitry that can convert a state change or ligand binding event to the receptor protein complex into an electronically processable variable or signal. The detection device can further include a socket into which the sensor chip can be inserted. The socket may provide appropriate optical and / or electrical and / or material flow connections necessary to operate and maintain the sensor chip and may allow the gas-permeable surface of the sensor chip to be in direct, and optionally constant, contact with the ambient medium atmosphere. The detection device may optionally include one or more of an outer housing, an on / off button located on the outer housing, a connection for plugging in a power source for battery charging embedded within the outer housing, perforations in the outer housing that allow ambient air to enter the outer housing, and a small screen or LED array embedded in the outer housing that enables the detection device to provide color-coded light signals describing the level of ambient air pollution and device status, such as battery status. The detection device may optionally include one or more of a speaker that enables the device to emit an acoustic signal when high levels of ambient air pollution are detected, a means for securing the device to, for example, clothing, bicycle, or backpack straps, a reversible photochromic coating or layer that is sensitive to UV radiation, and a radiochromic dye film that is sensitive to ionizing radiation.The detection device may optionally include one or more sources of physical signals, such as light sources, voltage sources, and current sources, which undergo a measurable change in their properties, e.g., intensity, amplitude, wavelength, and / or frequency, upon binding of the biologically active substance to the receptor-protein complex. A transducer and / or processing circuitry for detecting the measurable change in the physical signal and converting it into an electronically processable variable or signal may be largely or entirely contained within the detection device. The detection device may also optionally include one or more microfans or ventilation devices capable of actively sampling the ambient medium and supplying it to the sensor chip. The detection device may also include means for controlling the sampling flow rate generated by the microfan, which may be contained within the detection device. Optionally, the detection device may also include a Bluetooth transmitter and / or receiver, or means for communication with an external device, such as a user device. The detection device may also include one or more of a rechargeable battery pack, a microprocessor, microelectronics, and microoptics for operation of the sensor chip, monitoring the status of the sensor chip, and / or reading the chip's response to contamination of the ambient medium. Additionally, the detection device may include one or more of a temperature sensor, a heating unit or element, data storage, one or more sensors sensitive to humidity, pressure, VOCs, ozone, nitric oxide, carbon monoxide, particulate matter, or the like, and optional accessory components. The detection device may further include one or more of a GPS tracker, a clock, and means for sharing collected information regarding ambient medium quality, time, and / or location within a wider location, for example, a cloud-based network. Additionally, software or applications may be provided to the user device to control the detection system, detection device, and / or sensor chip, and to obtain sensor readings, alerts, and information regarding the current and predicted quality of the environment.Such software or applications may be configured to access the shared data and use it to, for example, estimate or predict, the quality of the ambient medium at a given location and time, for example, for purposes of route planning or developing exposure avoidance strategies. The software or applications may be configured, for example, to monitor cumulative personal exposure and compile reports on the success of exposure avoidance strategies, or to correlate exposure with health conditions, for example, as monitored by any compatible health monitoring device.

[0170] The following summarizes the technical concepts envisioned by the present disclosure for illustrative purposes, but should not be construed as limiting. Molecules, compounds, and / or agents present in the medium surrounding the detection device can diffuse into the reaction cell of the sensor chip. If the molecules are ligands for the receptor protein or receptor protein complex contained in the reaction cell, they can bind to the receptor protein complex and induce a change in the state of the receptor protein complex that can be measured. Potential technical solutions can include a gas-permeable membrane for the sensor chip, such as porous carbon paper used in fuel cells or micro-perforated fluoropolymers, both of which have low diffusion resistance and are nearly impermeable to aqueous liquids. The gas-permeable membrane can separate the surrounding medium from the reaction cell, which can contain, for example, a liquid, semi-solid, and / or gelatinous substrate containing the receptor protein complex. For example, the receptor protein complex can include the ligand-binding domain of a xenosensor protein, such as human AHR.

[0171] Alternatively, or in addition, at least a portion of the receptor protein complex may comprise at least one binding domain of an aryl hydrocarbon receptor or aryl hydrocarbon receptor protein. For example, at least a portion of the receptor protein complex may comprise at least a PAS (Per-ARNT-Sim) domain or the entire aryl hydrocarbon receptor protein, which may enable detection of materials, compounds, molecules, and / or agents, such as halogenated aromatic hydrocarbons, e.g., polychlorinated dibenzodioxins, dibenzofurans, and biphenyls, and / or polycyclic aromatic hydrocarbons, e.g., 3-ethylcholanthrene, benzo[a]pyrene, benzanthracene, and benzoflavone.

[0172] The receptor protein can be further immobilized at a specific location within the reaction cell of the sensor chip by covalently binding a low affinity ligand of the receptor protein complex to a functional surface of the reaction cell, such as the inner surface of the reaction cell or membrane. Binding of the ligand by the receptor protein complex can immobilize the receptor protein complex. Furthermore, medium or high affinity ligands, such as bioactive substances, can diffuse into the reaction cell and competitively bind to the receptor protein complex, which can then be released from the immobilization site.

[0173] Liberation events can be detected by various means. For example, the mass bound to the functional surface or another interior surface of the reaction cell can be monitored by a piezoelectric element, such as a quartz crystal microbalance. Alternatively, or additionally, the optical properties of the functional surface or another interior surface of the reaction cell can be monitored by measuring the interaction of molecules in close proximity to the surface of the waveguide or optical guide with an evanescent light field transmitted through that surface. Alternatively, or additionally, the presence of a liberated receptor protein complex, rather than liberation itself, can be detected. For example, the receptor protein complex can be linked to a detectable label when the receptor protein complex is freely diffusing within the reaction cell. Labeling can be achieved, for example, in the form of a fusion protein and green fluorescent protein (GFP), in which case detection can be based on fluorescence excitation of GFP and detection of emitted fluorescent light by one or more photodetectors in the detection device. Human heterologous sensor proteins, including fusion proteins containing green fluorescent protein (GFP), as well as various recombinant forms of human heterologous sensor proteins, can be cloned and used in molecular binding assays. Many potentially suitable low-affinity ligands, such as AHR ligands, can also be used. The sensitivity of the detection device may depend on the sensitivity of currently available detectors, such as piezoelectric or optical detectors, and processing circuitry. The device is sensitive enough to detect the release of the receptor protein complex. For piezoelectric detection, the receptor protein complex can be linked to a high-mass moiety, such as a nanoparticle or gold nanoparticle, resulting in a detection limit in the 50-femtomole concentration range. For optical detection, the signal per receptor protein complex can be increased by orders of magnitude by using a fluorescent mechanism, allowing for repeated excitation and emission of light. Some detailed examples of the operating principle at the molecular level are provided above and below in this specification. It should be noted that the chemical structure of the bioactive molecule or substance that binds to the receptor protein complex and triggers the sensor chip or detection device to report a detection signal may not be known. Therefore, the sensor chip and detection device according to the present disclosure are superior to sensors that selectively detect compounds known or suspected to have adverse effects on human health.On the other hand, bioactive molecules or substances must preferably bind to receptor protein complexes with sufficient affinity to induce measurable changes in the state of the protein complex. Therefore, it can be assumed that this will also be the case in living organisms, either triggering cellular defense mechanisms (when binding to heterologous sensor proteins) or activating cellular responses in the absence of endogenous signaling activity (when binding to hormone receptors). Therefore, sensor chips and detection devices are also superior to sensors that respond nonselectively to a wide range of compounds based on certain structural characteristics that may not be related to the compound's biological activity.

[0174] While in the case of conventional sensors, the unit of measurement may be the concentration of a given compound in the surrounding medium or the mass concentration of a component of a specified physical or chemical property, it should be noted that the concepts of mass per volume or parts per volume may not be suitably applied in the case of the sensor chips and detection devices described herein. The intensity of the reading or detection signal generated by the detection device may be the result of the concentration of biologically active substances in the surrounding medium and their affinity for the receptor protein complex. Therefore, the unit of measurement of the sensor chips and detection devices described herein can best be described as the receptor protein activation capacity of the surrounding medium, and hence the biological activity of the surrounding medium, depending, for example, on the type of receptor protein complex selected.

[0175] The following summarizes the details of the technical concepts envisioned by the present disclosure for illustrative purposes, but should not be construed as limiting. The sensor chip can have essentially any shape and size. The footprint of the sensor chip can be minimized, particularly in the case of portable detection devices. As an example, the sensor chip can potentially be approximately 1-10 cm long, 1-10 cm wide, and 0.5-2 cm thick, depending on the design of the detection device. The sensor chip includes a reaction cell and a compartment containing a substrate, such as an aqueous solution, an isotonic solution, a buffer solution, a semi-solid and / or gelatinous matrix, in which the receptor-protein complex and any additional proteins can maintain their native state. The substrate can be located on one or several sides of the reaction cell, separated from the surroundings by a membrane that is permeable to gas but not to water. The thickness and structure of the membrane material can be selected to minimize resistance to diffusion. Specifically, the membrane is preferably thin and / or has a high porosity. Optionally, the pores of the membrane can exclude water, and the pores can be filled with gas. The gas-permeable membrane can be protected from external physical damage, for example, by a rigid open lattice, which can be part of the chip housing and allow ambient gas from the medium to freely access the membrane. The lattice can be covered with an adhesive film or an airtight cover when the sensor chip is in its unused state. This can prevent molecules or agents from entering the cell from the ambient environment when not in operation. The cell can be resealable, which can extend the service life or life of the reaction cell.

[0176] Furthermore, the sensor chip may provide a small reservoir containing deionized water, since water can evaporate from the reaction cell by passing through the gas-permeable membrane. The reservoir may be connected to the reaction cell, and the diffusion of salts from the reaction cell may be prevented by the presence of a semipermeable membrane at the connection point. In one example, the reservoir may be a small flexible blister that does not offer any significant resistance to contraction even if water attempts to exit toward the reaction cell. The reservoir may be surrounded by a rigid housing, which may include holes through which ambient air or media can enter the housing when higher osmolality in the reaction cell causes water to be drawn from the flexible blister toward the reaction cell. Alternatively, or additionally, flexibility in the volume of the water reservoir may be achieved by a movable piston.

[0177] In one example, the same water reservoir or another reservoir can serve to prime the sensor chip, particularly if the receptor-protein complex and any additional proteins that may be present maintain their functionality upon lyophilization and reconstitution. Primement can be achieved by disrupting a water-impermeable barrier or membrane between the reservoir and the reaction cell, allowing water to enter the reaction cell and reconstitute the receptor-protein complex. This process can be driven by the higher osmolality of the reaction cell and will continue until the osmotic pressure within the reaction cell is counteracted by the rigid lattice covering its housing and, optionally, the gas-permeable membrane.

[0178] Additionally, the sensor chip may provide electrical and / or optical contacts or connections through which it can be connected to a detection device when attached.

[0179] The receptor protein complex can be cloned, expressed, isolated, and / or purified using standard molecular biology methods. Depending on the molecular operation principle of the sensor chip, auxiliary proteins that i) bind to the receptor protein complex and dissociate from it upon ligand binding in living cells, or ii) bind to the receptor protein complex upon ligand binding, or iii) chemically modify the receptor protein upon ligand binding, or iv) are chemically modified by the receptor protein complex upon ligand binding can be cloned and isolated and further included in the sensor chip.

[0180] In this functional device, receptor protein complexes can be present in the reaction cell of a sensor chip. Depending on the molecular operating principle of the sensor chip, they can be immobilized, i.e., confined to an area or surface inside the reaction cell, or dissolved in a substrate contained therein. Furthermore, depending on the operating principle of the sensor chip at the molecular level, the dissolved or immobilized receptor protein complexes can be in a monomeric form (not complexed with other proteins), as a homodimer (two receptor proteins bound together), or in the form of a multiprotein complex.

[0181] In examples where the receptor protein complex is immobilized on a region or surface of the reaction cell, the receptor protein can preferably be immobilized as close as possible to where components of the surrounding medium enter the cell. For example, this can be the gas-permeable membrane itself, particularly on the side of the membrane facing the inside of the reaction cell. Such an embodiment can minimize the delay between components of the surrounding medium, such as a bioactive substance, entering the reaction cell and their binding to the receptor protein complex, while at the same time maximizing the likelihood of binding, since the point of entry is in close proximity to the receptor protein complex.

[0182] Immobilization of a receptor protein complex can be achieved by covalently binding the receptor protein complex, or a member of a homodimer, or one or more members of a multiprotein complex to a membrane. The covalent binding may be such that it does not alter the structure of the ligand-binding domain and / or protein-protein interaction site, nor may it sterically affect protein or ligand binding. Alternatively, or additionally, this can be achieved by immobilizing a low-affinity ligand of the receptor protein complex (when only one type of receptor protein is present) or a mixture of low-affinity ligands (when several different types of receptor proteins are present). Alternatively, or additionally, this can be achieved by covalently binding a molecule that binds to a specific region or domain of the receptor protein complex or to one or several of the additional proteins present in the reaction cell and bound to the receptor protein complex. Thus, the target region or domain of the binding protein may not be identical to the ligand-binding site or the interaction site between different proteins present in the reaction cell. Examples include the immobilization of monoclonal antibodies specific for a particular epitope of the protein to be immobilized, or nitrilotriacetic acid-conjugated nickel ions when the protein complex to be immobilized contains a histidine tag capable of chelating nickel ions. 2+ Examples include immobilization of ions.

[0183] Multiple means for immobilizing proteins in the reaction cell can be implemented. These can serve the same purpose, such as immobilizing a protein complex prior to ligand binding, or different purposes, such as binding a protein complex bound to a ligand or bioactive substance. Also, several types of receptor protein complexes can be present on the same sensor chip, allowing for broader chemical specificity of the sensor. Different labels can be linked to the receptor protein complex and / or additional proteins that interact with the receptor protein complex, allowing for determination of which of several receptor protein complexes used has bound to a ligand or corresponding bioactive substance present in its surroundings. Alternatively or additionally, various chips containing different receptor protein complexes, thus providing different specificities, can be available, optionally all matching the sockets present on the detection device.

[0184] Once activated, a sensor chip can have a limited service life or lifetime due to receptor protein complex depletion, as the amount of receptor protein available for environmental monitoring can decrease over time. This decrease can be attributed to two mechanisms: i) at some point, all available receptor protein will bind to molecules that enter the reaction cell from the environment; and ii) receptor proteins have a fixed half-life, even in the absence of binding molecules or agents and under optimized physicochemical conditions in the sensor chip substrate. Receptor protein complex depletion by the former mechanism can be a function of cumulative detected contamination and can be calculated based on the known amount of receptor protein complex initially present on the sensor chip. Receptor protein complex depletion by the latter mechanism can be a function of receptor protein stability under the physicochemical conditions in the reaction cell. This can be determined by parameters specific to the sensor chip, such as the receptor protein complex and substrate composition employed, as well as parameters specific to the use of the detection device, such as the temperature to which the sensor chip is exposed during its lifetime. Depletion of the receptor protein complex can be determined continuously or at defined time intervals by the detection device. In embodiments using immobilized receptor protein complexes, for example, this can be accomplished by measuring a property such as the impedance of the absorbance of a layer of immobilized receptor protein complexes. Alternatively, or additionally, parameters specific to the sensor chip can be determined as part of development or production. Furthermore, parameters related to the usage of the detection device or sensor chip can be measured throughout the life of the chip.

[0185] For example, the sensor chip may carry a chip identifier that can enable a software application used to operate the detection device, e.g., installed on the user device or on the detection device, to read the chip's usage history. Preferably, the chip identifier can be automatically detected by the detection device upon chip insertion. Alternatively, or additionally, the chip may carry a physical identifier, such as a chip ID number, that can be entered by the user upon inserting the chip into the detection device. The software can estimate the depletion of receptor proteins on the sensor chip from the usage history, sensor type, and cumulative detected contamination or exposure, and notify the user when it is time to replace the chip.

[0186] Because the sensor chip has a limited lifespan and for reasons of sustainability and product cost, the sensor chip is preferably made from the smallest possible amount of material, preferably recycled and recyclable materials. The chip preferably contains only electrical and / or optical leads or connectors, and no additional electronic sensor elements, such as diodes, photodetectors, or processors, involved in signal generation, capture, or processing. However, alternatively, one or more of these elements may be included in the sensor chip.

[0187] In the following, the sensor response time is exemplarily estimated. The basic operating principle may include transport of a bioactive substance from the surrounding medium to the boundary layer in a gas-permeable membrane, transport across the boundary layer to the gas-permeable membrane, diffusion of the bioactive substance through the gas-permeable membrane, diffusion of the bioactive substance to a receptor protein complex, binding of the bioactive substance to the receptor protein complex, optionally diffusion of the receptor protein complex to a detection site, and finally detection of a state change induced upon binding.

[0188] Transport of bioactive substances from the surrounding medium to the boundary layer of the gas-permeable membrane can be driven by convection, i.e., the surrounding medium can be actively or passively brought to the boundary layer of the gas-permeable membrane. For specific device dimensions and sampling rates of approximately 0.5-10 mL / s, this can depend on the size of the device, but mass transfer, whether passive or active, can be expected to cause a delay of approximately 1-5 seconds compared to the generation of bioactive substances around the sensor chip.

[0189] Transport across the boundary layer to and across the gas permeable membrane is This can depend on the Brownian motion and diffusion coefficient D of the molecule or bioactive substance being considered according to TIFF0007727102000001.tif8170, where m(x) is the mean square displacement in the x direction (e.g., toward the gas-permeable membrane) and Δt is time. Diffusion coefficients for relevant organic molecules and bioactive substances can be in the range of 0.05 cm / sec (at atmospheric, ambient conditions). Assuming a 2 mm thickness of the open lattice that makes up the boundary layer, transport through the lattice combs into the gas-permeable membrane can be expected to occur in approximately 2 seconds.

[0190] Furthermore, transport across gas-permeable membranes may follow the same physical principles, but depending on the pore size of the membrane, the diffusion coefficient D should be replaced by the Knudsen diffusion coefficient; that is, the effective diffusion coefficient decreases as molecular collisions with the pore walls become more frequent than collisions between molecules in the fluid. Furthermore, depending on the type of membrane, the membrane pores may be filled with liquid or gas, so the diffusion coefficient should be taken accordingly (diffusion coefficients in water are orders of magnitude smaller). Assuming the pore size in the membrane is approximately 0.2 μm, which is within about half the mean free path of molecules in air at 25°C, the pores are filled with air, and the Knudsen diffusion coefficient is approximately 0.025 cm. 2 / sec range. Thus, a 200 μm thick membrane can cause an additional delay of about 0.2 seconds.

[0191] The kinetics of diffusion of the bioactive substance to the receptor protein complex may cause additional delays. This may be negligible in embodiments where the receptor protein complex is immobilized on a gas-permeable membrane. In embodiments where the receptor protein complex is dissolved in the reaction chamber, the diffusion coefficient in water and the average distance between the gas-permeable membrane and the location of the dissolved receptor protein complex can be estimated as described above. The diffusion coefficient of relevant organic molecules in water is in the range of 10-5 cm. 2 The reaction time can be in the range of 1 / sec, and the average distance between the dissolved receptor-protein complex and the gas-permeable membrane can be estimated to be half the reaction cell diameter. Therefore, the reaction cell dimensions can be in the range of 0.1 mm or less. For larger dimensions (average distance of 1 mm, for example, causing a delay of several thousand seconds), the substrates present in the reaction cell can be actively mixed, for example, by generating convection within the reaction cell, by non-uniform heat supply, or by introducing microfluidic circulation.

[0192] The actual binding between the bioactive substance and the receptor-protein complex can be a rapid process, so estimation of response time is not necessary. Furthermore, with regard to the diffusion of the receptor-protein complex to the detection site, the same considerations as those described above for the diffusion of the bioactive substance to the receptor-protein complex apply, except that the diffusion coefficient of the protein complex is typically about ten times smaller than the diffusion coefficient of the organic molecule or bioactive substance (10-6 cm). 2 / sec range. Furthermore, detection typically occurs immediately and does not contribute to a delay between the onset of a bioactive substance and the generation of a sensor signal. [Example]

[0193] 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 any other example, embodiment, or aspect described herein.

[0194] Example 1: 1. A sensor chip operably connectable to a detection device for detecting one or more biologically active substances in a surrounding medium, the sensor chip comprising: a reaction cell containing a plurality of receptor protein complexes; a membrane separating the reaction cell from the surrounding medium and permeable to one or more biologically active substances; A sensor chip in which the receptor protein complex is configured to bind to one or more biologically active substances in the reaction cell, thereby inducing a detectable state change in at least a portion of the receptor protein complex. Example 2: 2. The sensor chip of Example 1, wherein the detectable change in state of the at least a portion of the receptor protein complex is indicative of the presence of one or more biologically active substances in the surrounding medium. Example 3: The sensor chip of any one of the preceding embodiments, wherein the change in state of at least a portion of the receptor protein complex is associated with one or more of a change in conformational state of at least a portion of the receptor protein complex, a change in localization of at least a portion of the receptor protein complex within the reaction cell, a change in position of at least a portion of the receptor protein complex within the reaction cell, a change in composition of at least a portion of the receptor protein complex, a change in mass of at least a portion of the reaction cell, a change in physical properties of at least a portion of the receptor protein complex, a change in physical properties of at least a portion of the reaction cell, a change in optical properties of at least a portion of the reaction cell, a change in chemical properties of at least a portion of the receptor protein complex, a change in chemical properties of a substrate contained within the reaction cell, a change in conductivity of a substrate contained within the reaction cell, or a change in concentration of free fluorescent molecules or light-absorbing molecules within at least a portion of the reaction cell. Example 4: The sensor chip of any one of the preceding embodiments, wherein the receptor protein complex is configured to change position within the reaction cell upon binding to one or more biologically active substances. Example 5: The sensor chip of any one of the preceding embodiments, wherein the receptor protein complex is configured to dissociate into one or more components upon binding to one or more biologically active agents. Example 6: At least a portion of the receptor protein complex is bound or immobilized to at least one functional surface of the reaction cell; and The sensor chip of any one of the preceding embodiments, wherein the receptor protein complex is configured to dissociate from at least one functional surface upon binding to one or more biologically active substances. Example 7: The sensor chip of any one of the preceding embodiments, wherein at least a portion of the receptor protein complex is covalently bound to at least one functional surface of the reaction cell. Example 8: A sensor chip described in any one of the preceding examples, wherein at least a portion of the receptor-protein complex is bound or immobilized to at least one functional surface of the reaction cell by a low-affinity ligand covalently bound to at least one functional surface of the reaction cell. Example 9: 9. The sensor chip of any one of Examples 6 to 8, wherein the receptor-protein complex is electrostatically bound to at least one functional surface of the reaction cell. Example 10: 10. The sensor chip according to any one of Examples 6 to 9, wherein at least one functional surface of the reaction cell is defined by an inner surface of the membrane facing the reaction cell. Example 11: 11. The sensor chip of any one of Examples 6 to 10, wherein the at least one functional surface comprises an inner surface of a reaction cell facing the membrane. Example 12: 12. The sensor chip of any one of Examples 6 to 11, wherein the at least one functional surface comprises an inner surface of a reaction cell positioned opposite the membrane. Example 13: The sensor chip of any one of the preceding embodiments, wherein the surrounding medium comprises ambient air. Example 14: The sensor chip of any one of the preceding embodiments, wherein the surrounding medium comprises water. Example 15: the membrane includes an outer surface configured to contact the surrounding medium; and The sensor chip of any one of the preceding embodiments, wherein the membrane comprises an inner surface facing the reaction cell. Example 16: The sensor chip of any one of the preceding embodiments, wherein the one or more biologically active substances comprise an exogenous agent. Example 17: The sensor chip of any one of the preceding embodiments, wherein the reaction cell contains one or more of a liquid, a gelatinous, and a semi-solid substrate. Example 18: The sensor chip of Example 17, wherein the substrate is configured to maintain the receptor protein complex in a native state. Example 19: 19. The sensor chip of any one of Examples 17 and 18, wherein the substrate comprises at least one of an aqueous solution, an isotonic solution, and a buffer solution. Example 20: 20. The sensor chip of any one of Examples 17 to 19, wherein the substrate comprises a stabilizing protein for stabilizing the receptor protein complex. Example 21: 21. The sensor chip of any one of Examples 17 to 20, wherein the substrate comprises a surfactant molecule or surfactant molecule complex. Example 21: 22. The sensor chip of any one of Examples 17 to 21, wherein the substrate comprises at least one of Tween or Triton X-100. Example 23: the membrane is permeable to gases, and / or The sensor chip of any one of the preceding embodiments, wherein the membrane is impermeable to water or aqueous liquids. Example 24: The sensor chip of any one of the previous embodiments, wherein the membrane comprises a plurality of pores, preferably filled with a gas to exclude water. Example 25: The sensor chip of any one of the previous embodiments, wherein the membrane comprises at least one of a porous carbon paper material and a perforated fluoropolymer. Example 26: The sensor chip of any one of the preceding embodiments, further comprising a grating covering at least a portion of the outer surface of the membrane. Example 27: The sensor chip of any one of the preceding embodiments, further comprising a sealing cover configured to cover at least a portion of the outer surface of the membrane and to prevent the membrane from contacting the surrounding medium. Example 28: 27. The sensor chip of Example 26, wherein the sealing cover comprises an adhesive film. Example 29: The sensor chip according to any one of the previous embodiments, wherein the reaction cell is sealable and / or resealable by covering at least a part of the outer surface of the membrane with a sealing cover. Example 30: 30. The sensor chip of any one of 27 to 29, wherein the sealing cover is airtight. Example 31: The sensor chip of any one of the preceding embodiments, wherein the sensor chip is configured and sized to be at least partially inserted into a detection device. Example 32: The sensor chip of any one of the preceding embodiments, wherein the sensor chip is configured and sized to be at least partially inserted into a socket of a detection device. Example 33: A sensor chip described in any one of the preceding embodiments, wherein the sensor chip has at least one surface feature on an outer surface of the sensor chip housing, and the at least one surface feature of the sensor chip is formed complementarily to at least one surface feature of the socket to ensure correct positioning of the sensor chip within the socket. Example 34: 34. The sensor chip of example 33, wherein at least one surface feature of the sensor chip is configured to engage with at least one surface feature of the socket to secure the sensor chip within the socket. Example 35: The sensor chip of any one of the previous embodiments, wherein the sensor chip comprises one or more magnets for magnetically coupling the sensor chip to a detection device. Example 36: The sensor chip of any one of the preceding embodiments, wherein the change in state of at least a portion of the receptor protein complex can be determined based on optical measurements, based on detection of fluorescent light, based on fluorescent excitation of one or more components of the receptor protein complex, based on light scattering, based on determining the electrical conductivity of a substrate contained within the reaction cell, based on electrochemical processes occurring within the reaction cell, based on determining one or more optical properties of at least one functional surface of the reaction cell, based on absorption of electromagnetic radiation, based on determining the mass of at least one functional surface of the reaction cell, based on determining the mass of the receptor protein complex bound or immobilized on at least one functional surface of the reaction cell, and based on surface plasmon resonance on at least one functional surface of the reaction cell. Example 37: The sensor chip of any one of the preceding embodiments, further comprising one or more connectors for operably coupling the sensor chip to a detection device. Example 38: The sensor chip of Example 36, wherein the sensor chip is connectable to a detection device via one or more connectors, such that a change in state of at least a portion of the receptor protein complex upon binding to one or more biologically active substances is detectable by the detection device. Example 39: A sensor chip described in any one of Examples 37 to 38, wherein the one or more connectors include at least one optical connector configured to couple electromagnetic radiation from a detection device to the reaction cell for optically detecting a change in state of at least a portion of the receptor protein complex upon binding to one or more biologically active substances. Example 40: 39. The sensor chip of Example 38, wherein the one or more connectors comprise at least one additional optical connector for coupling electromagnetic radiation out of the reaction cell. Example 41: A sensor chip described in any one of Examples 38 to 40, wherein at least one optical connector comprises at least one opening disposed within the housing of the sensor chip. Example 42: 42. The sensor chip of example 41, wherein at least one opening is sealed with a layer of material that is semi-transparent to electromagnetic radiation of a predetermined wavelength. Example 43: 43. The sensor chip of any one of Examples 41 to 42, wherein at least one opening is oriented parallel to the longitudinal axis of the reaction cell. Example 44: The sensor chip of any one of the preceding embodiments, further comprising at least one optical guide for guiding electromagnetic radiation through the reaction cell to optically detect a change in state of at least a portion of the receptor protein complex upon binding to one or more biologically active substances. Example 45: 45. The sensor chip of example 44, wherein at least one optical guide is aligned with and optically coupled to at least one optical connector of the sensor chip. Example 46: 46. The sensor chip of any one of Examples 44 to 45, wherein at least one optical guide extends through the reaction cell parallel to a longitudinal axis of the reaction cell. Example 47: A sensor chip described in any one of Examples 44 to 46, wherein the sensor chip comprises at least two optical guides and at least one reflective element arranged at the ends of the at least two optical guides, and the at least one reflective element optically couples the at least two optical guides. Example 48: A sensor chip as described in Example 47, wherein each of the at least two optical guides is optically coupled to at least one optical connector of a sensor deceive arranged at the end of each optical guide opposite at least one reflective element. Example 49: The sensor chip of any one of Examples 37 to 48, wherein the one or more connectors comprise at least one electrical connector for electrically coupling the sensor chip to a detection device. Example 50: The sensor chip of any one of the preceding Examples, further comprising one or more electrodes disposed at least partially within the reaction cell and configured to determine the conductivity of a substrate or composition within the reaction cell. Example 51: The sensor chip of any one of the preceding embodiments, further comprising at least one detection window that is semi-transparent to electromagnetic radiation emitted and / or scattered by at least one or more components of the receptor protein complex. Example 52: at least one detection window is semi-transparent to fluorescent light emitted by at least one or more components of the receptor protein complex; and / or 52. The sensor chip of Example 51, wherein at least one detection window is opaque to fluorescence excitation light. Example 53: 53. The sensor chip of any one of Examples 51 to 52, wherein at least one detection window is positioned opposite and / or facing the membrane. Example 54: A sensor chip described in any one of Examples 51 to 53, wherein the inner surface of at least one detection window facing the reaction cell is at least partially coated with a molecular capture complex configured to bind to at least a component of a receptor protein complex, thereby allowing receptor protein complexes bound to one or more biologically active substances to be captured on the inner surface. Example 55: The sensor chip of Example 54, wherein the molecular capture complex comprises streptavidin. Example 56: 56. The sensor chip of any one of Examples 51 to 55, wherein the inner surface of at least one detection window facing the reaction cell is at least partially coated with chelated nickel ions. Example 57: A sensor chip described in any one of Examples 51 to 56, wherein the inner surface of at least one detection window facing the reaction cell is at least partially coated with a quenching molecule for quenching fluorescent light emitted by at least one component of the receptor protein complex. Example 58: A sensor chip according to any one of the preceding examples, wherein the inner surface of the membrane facing the reaction cell is at least partially coated with a quenching molecule for quenching fluorescent light emitted by at least one component of the receptor protein complex. Example 59: The sensor chip according to any one of the preceding embodiments, wherein the sensor chip and / or the reaction cell has an elongated shape. Example 60: The sensor chip and / or the reaction cell have an elongated shape, and The sensor chip of any one of the previous embodiments, wherein the membrane is disposed on a longitudinal side of the sensor chip. Example 61: the reaction cell has a rectangular cross section, and / or The sensor chip according to any one of the preceding embodiments, wherein the reaction cell is formed as a parallelepiped. Example 62: the reaction cell has a circular, oval, or elliptical cross section; and / or The sensor chip of any one of the preceding embodiments, wherein the reaction cell is tubular in shape. Example 63: The sensor chip of any one of the preceding embodiments, wherein the membrane at least partially surrounds the reaction cell along its periphery. Example 64: The sensor chip of any one of the preceding embodiments, further comprising at least one reservoir fluidly connectable to the reaction cell, the at least one reservoir configured to supply deionized water to the reaction cell. Example 65: 65. The sensor chip of example 64, wherein at least one reservoir is at least partially filled with deionized water. Example 66: 66. A sensor chip described in any one of Examples 64 to 65, wherein at least a portion of the wall of at least one reservoir is displaceable, flexible, or movable so that the volume of the reservoir is adjustable. Example 67: 67. The sensor chip of any one of Examples 64 to 66, wherein at least a portion of at least one reservoir is formed as a flexible bag or a flexible blister. Example 68: 68. The sensor chip of any one of Examples 64 to 67, further comprising at least one movable piston configured to adjust the volume of at least one reservoir. Example 69: At least one reservoir is surrounded by a portion of the housing of the sensor chip; and 69. The sensor chip of any one of Examples 64 to 68, wherein the portion of the housing comprises at least one opening for pressure equalization. Example 70: 70. The sensor chip of any one of Examples 64 to 69, wherein at least one reservoir is fluidly coupled to the reaction cell by a semipermeable membrane that blocks salt from diffusing from the reaction cell into the reservoir. Example 71: 71. The sensor chip of any one of Examples 64 to 70, further comprising at least one blocking element configured to block fluid communication between the reaction cell and the at least one reservoir. Example 72: 72. The sensor chip of Example 71, wherein the sensor chip is activatable in response to unblocking fluid communication between the reaction cell and the at least one reservoir using at least one blocking element. Example 73: 73. The sensor chip of any one of Examples 71 to 72, wherein the at least one blocking element comprises a water-impermeable membrane disposed between the at least one reservoir and the reaction cell. Example 74: The sensor chip of Example 73, wherein the sensor chip is activatable in response to rupturing at least a portion of the water-impermeable membrane. Example 75: 75. The sensor chip of any one of Examples 71 to 74, wherein the at least one blocking element comprises a movable pin operable to block or unblock fluid communication between the reaction cell and the at least one reservoir. Example 76: 76. The sensor chip of Example 75, wherein the sensor chip is actuable in response to moving the movable pin, thereby unblocking fluid communication between the reaction cell and at least one reservoir. Example 77: A sensor chip according to any one of the preceding examples, wherein the receptor protein complexes each comprise at least one ligand binding domain of a receptor protein configured to bind to one or more biologically active substances and to undergo a state and / or conformation change upon binding to one of the biologically active substances. Example 78: The sensor chip of any one of the preceding Examples, wherein at least a portion of the receptor protein complex comprises multiple ligand binding domains of one or more receptor proteins. Example 79: 10. The sensor chip of any one of the preceding embodiments, wherein at least some of the receptor protein complexes comprise a plurality of different ligand binding domains configured to bind different types of biologically active substances. Example 80: 79. The sensor chip of any one of Examples 76 to 78, wherein the receptor protein is a heterologous sensor protein or a hormone receptor protein. Example 81: The sensor chip of any one of the preceding Examples, wherein the receptor protein complexes each comprise at least one ligand binding domain of a receptor protein selected from the group consisting of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, estrogen receptor, and aryl hydrocarbon receptor. Example 82: The sensor chip of any one of the preceding Examples, wherein at least some of the receptor protein complexes comprise recombinant or non-recombinant proteins. Example 83: The sensor chip of any one of the preceding Examples, wherein the receptor protein complex comprises at least a portion of a monomeric receptor protein, a homodimeric receptor protein complex, or a heterodimeric receptor protein complex, respectively. Example 84: The sensor chip of any one of the preceding embodiments, wherein the receptor protein complex comprises at least portions of different types of receptor proteins configured to bind different types of biologically active substances. Example 85: A sensor chip described in any one of the preceding examples, wherein at least a portion of the receptor protein complexes comprise organic or inorganic moieties that dissociate from the remainder of the respective receptor protein complex upon binding to one or more biologically active substances. Example 86: A sensor chip described in any one of the preceding examples, wherein the receptor protein complexes comprise at least one fluorescent label that dissociates from the remainder of the respective receptor protein complex upon binding to one or more biologically active substances. Example 87: 10. The sensor chip of any one of the preceding embodiments, wherein at least some of the receptor protein complexes comprise multiple fluorescent labels of the same or different types. Example 88: 87. The sensor chip of any one of Examples 85 to 86, wherein at least one fluorescent label is a fluorescent dye or green fluorescent protein. Example 89: The sensor chip of any one of the preceding embodiments, wherein the receptor protein complexes comprise nanoparticles that dissociate from the remainder of the respective receptor protein complex upon binding to one or more biologically active substances. Example 90: The sensor chip of any one of the preceding embodiments, wherein the receptor protein complex comprises an affinity tag configured to bind to a molecular capture complex disposed in the reaction cell. Example 91: The sensor chip of any one of the preceding Examples, further comprising a chip identifier for identifying the type of sensor chip and / or the type of receptor protein complex that the sensor chip comprises. Example 92: 92. The sensor chip of Example 91, wherein the chip identifier is readable by a user device and / or readable by a detection device. Example 93: A sensor chip described in any one of Examples 91 or 92, wherein the chip identifier contains information or data indicating the type of sensor chip and / or the type of receptor protein complex that the sensor chip contains. Example 94: The sensor chip of any one of the preceding embodiments, wherein the chip identifier comprises one or more of a barcode, a QR code, an RFID tag, a label, and data storage. Example 95: The sensor chip of any one of the preceding embodiments, further comprising data storage configured to store historical data indicative of usage or remaining life of the sensor chip. Example 96: 96. The sensor chip of Example 95, wherein the data storage is configured to store one or more operating parameters indicative of the usage or remaining life of the sensor chip. Example 97: 97. The sensor chip of any one of Examples 95 to 96, wherein the data storage is accessible by a detection device when the sensor chip is operably coupled to the detection device. Example 98: The sensor chip of any one of the preceding embodiments, wherein the sensor chip comprises a plurality of reaction cells. Example 99: The sensor chip of any one of the preceding embodiments, wherein the plurality of reaction cells comprises different types of receptor protein complexes configured to bind different types of biologically active substances. Example 100: The sensor chip of any one of the preceding embodiments, further comprising one or more sensors configured to determine a change in state of at least a portion of the receptor protein complex. Example 101: The sensor chip of any one of the preceding embodiments, further comprising a processing circuit coupled to the one or more sensors and configured to provide a detection signal indicative of a determined change in state of at least a portion of the receptor protein complex. Example 102: Use of a sensor chip according to any one of the preceding examples for detecting one or more biologically active substances. Example 103: 102. A detection device operably coupled to at least one sensor chip according to any one of Examples 1 to 101 for detecting one or more biologically active substances in a surrounding medium, the detection device comprising: at least one sensor configured to determine a change in state of at least a portion of a receptor protein complex within a reaction cell of at least one sensor chip, the change in state being induced by binding of the one or more receptor protein complexes with one or more biologically active substances that pass from the surrounding medium through a membrane of the sensor chip into the reaction cell of the sensor chip; and A detection device comprising a processing circuit coupled to at least one sensor, the processing circuit configured to provide a detection signal indicative of the presence of one or more biologically active substances in a surrounding medium based on determining a change in state of at least a portion of a receptor protein complex. Example 104: 1. A detection device for detecting one or more biologically active substances in a surrounding medium, the detection device comprising: A housing configured to at least partially receive at least one sensor chip according to any one of Examples 1 to 101 and to operably couple a detection device to the at least one sensor chip; and a processing circuit configured to provide a detection signal indicative of the presence of one or more biologically active substances in the surrounding medium based on determining a change in state of at least a portion of the receptor protein complex in the reaction cell of at least one sensor chip, wherein the change in state is induced by binding of the one or more receptor protein complexes with one or more biologically active substances that enter the reaction cell of the sensor chip from the surrounding medium through the membrane of the sensor chip. Example 105: the surrounding medium includes ambient air; and / or A detection device described in any one of Examples 103 and 104, wherein the detection device is an environmental monitoring device for monitoring the quality of ambient air. Example 106: 106. The detection device according to any one of Examples 103 to 105, wherein the detection device is a stationary device and / or a desktop device. Example 107: 106. The detection device of any one of Examples 103 to 105, wherein the detection device is a portable device, a mobile device, and / or a handheld device. Example 108: 108. The detection device according to any one of Examples 103 to 107, wherein the detection signal is an electronically processable signal. Example 109: A detection device described in any one of Examples 103 to 108, wherein the detection signal indicates the amount of one or more biologically active substances per volume of the surrounding medium, the mass of the biologically active substance per volume of the surrounding medium, the concentration of the biologically active substance in the surrounding medium, the ability of the surrounding medium to activate a receptor protein, and the biological activity of the surrounding medium. Example 110: 110. The detection device of any one of Examples 103 to 109, wherein the detection device is configured to at least partially receive at least one sensor chip. Example 111: 111. The detection device of any one of Examples 103 to 110, wherein the detection device is mechanically coupleable to the sensor chip. Example 112: 112. The detection device of any one of examples 103 to 111, wherein the detection device is magnetically coupleable to the sensor chip. Example 113: 113. The detection device according to any one of Examples 103 to 112, wherein the detection device comprises at least one socket configured to at least partially receive at least one sensor chip. Example 114: A detection device as described in Example 113, wherein at least one socket is configured to at least partially receive at least one sensor chip such that the housing of the detection device at least partially surrounds the at least one sensor chip. Example 115: A detection device described in any one of Examples 113 to 114, wherein at least one socket has at least one surface feature formed complementary to at least one surface feature of the sensor chip, thereby ensuring correct positioning of the sensor chip within the at least one socket. Example 116: 116. The detection device of embodiment 115, wherein at least one surface feature of at least one socket includes one or more guides for positioning the sensor chip within the socket. Example 117: A detection device described in any one of Examples 115 to 116, wherein at least one surface feature of at least one socket is configured to at least partially engage with at least one surface feature of the sensor chip, thereby enabling the sensor chip to be removably fixed within the socket. Example 118: 118. A detection device according to any one of Examples 103 to 117, wherein the detection device comprises a plurality of sockets configured to receive a plurality of sensor chips of the same or different types. Example 119: 119. The detection device of any one of Examples 103 to 118, wherein the detection device comprises one or more magnets for magnetically coupling the sensor chip to the detection device. Example 120: The detection device described in any one of Examples 103 to 119, wherein the detection device is configured to determine a change in state of at least a portion of the receptor protein complex based on optical measurements, based on detection of fluorescent light, based on fluorescence excitation of one or more components of the receptor protein complex, based on light scattering, based on determining the conductivity of a substrate contained within the reaction cell of the sensor chip, based on electrochemical processes occurring within the reaction cell, based on determining one or more optical properties of at least one functional surface of the reaction cell, based on determining absorption of electromagnetic radiation, based on determining the mass of at least one functional surface of the reaction cell, based on determining the mass of the receptor protein complex bound or immobilized on at least one functional surface of the reaction cell, and based on surface plasmon resonance on at least one functional surface of the reaction cell. Example 121: A detection device described in any one of Examples 103 to 120, wherein the processing circuit is configured to determine the presence of one or more biologically active substances in the surrounding medium based on detecting a change in the position of one or more receptor proteins in the reaction cell upon binding to one or more biologically active substances using at least one sensor of the sensor chip or detection device. Example 122: a detection device configured to determine one or more of the presence, number, mass, density, and mass density of receptor-protein complexes dissolved in the substrate of the reaction cell of the at least one sensor chip; and / or A detection device described in any one of Examples 103 to 121, wherein the detection device is configured to determine one or more of the presence, number, mass, density, and mass density of receptor protein complexes dissolved in the substrate of the reaction cell of at least one sensor chip based on determining a change in at least one of the optical signal and the electrical signal transmitted to the sensor chip. Example 123: the receptor protein complex is configured to dissociate from at least one functional surface of the reaction cell upon binding to one of the biologically active substances; and A detection device described in any one of Examples 103 to 122, wherein the detection device is configured to determine one or more of the number, mass, density, and mass density of receptor protein complexes immobilized on at least one functional surface of the reaction cell or released from at least one functional surface of the reaction cell. Example 124: A detection device described in any one of Examples 103 to 123, wherein the detection device includes one or more piezoelectric elements configured to determine the mass of a receptor protein complex fixed to or released from at least one functional surface of the reaction cell, thereby detecting one or more biologically active substances in the surrounding medium. Example 125: A detection device as described in Example 124, wherein one or more piezoelectric elements are configured to determine the mass of a receptor protein complex fixed to or released from at least one functional surface of the reaction cell based on determining the mass of one or more components of a receptor protein complex bound to an inner surface of the reaction cell arranged toward at least one functional surface of the reaction cell. Example 126: one or more piezoelectric elements are mechanically coupleable to one or more functional surfaces of the reaction cell of the sensor chip; and / or A detection device described in any one of Examples 124 to 125, wherein one or more piezoelectric elements are mechanically coupled to one or more inner surfaces of a reaction cell of a sensor chip arranged toward one or more functional surfaces of the reaction cell. Example 127: the receptor protein complex comprises at least one fluorescent label; and A detection device described in any one of Examples 103 to 124, wherein the detection device is configured to detect one or more biologically active substances based on exciting one or more fluorescent labels and detecting fluorescent light emitted by the one or more fluorescent labels. Example 128: the receptor protein complexes include at least one fluorescent label that dissociates from the remainder of the respective receptor protein complex upon binding to one or more of the biologically active substances; and A detection device described in any one of Examples 103 to 127, wherein the detection device is configured to detect one or more biologically active substances based on exciting one or more fluorescent labels dissociated from one or more receptor protein complexes and detecting fluorescent light emitted by the one or more dissociated fluorescent labels. Example 129: the detection device includes one or more light sources configured to excite the one or more fluorescent labels; and 129. The detection device of any one of Examples 127 to 128, wherein the detection device comprises one or more photodetectors configured to detect fluorescent light emitted by the one or more fluorescent labels. Example 130: the detection device includes one or more light sources configured to illuminate at least a portion of the reaction cell; and A detection device described in any one of Examples 103 to 129, wherein the detection device comprises one or more photodetectors configured to detect light scattered by one or more components of a receptor protein complex in the reaction cell. Example 131: A detection device described in any one of Examples 129 to 130, wherein one or more photodetectors are positioned adjacent to the detection device socket to at least partially receive the sensor chip and detect electromagnetic radiation transmitted outside the reaction cell. Example 132: 132. The detection device of any one of Examples 129 to 131, wherein one or more photodetectors are positioned opposite the detection window of the sensor chip. Example 133: A detection device described in any one of Examples 129 to 132, wherein the one or more light sources are positioned adjacent to a socket of the detection device for at least partially receiving the sensor chip so that electromagnetic radiation emitted by the one or more light sources can be coupled into the reaction cell. Example 134: 134. The detection device of any one of Examples 129 to 133, wherein one or more light sources are configured to couple electromagnetic radiation into the reaction cell via one or more optical connectors on the sensor chip. Example 135: the detection device includes one or more light sources arranged to couple electromagnetic radiation into one or more optical guides that traverse at least a portion of the reaction cell of the sensor chip; and A detection device described in any one of Examples 103 to 134, wherein the detection device includes one or more optical detectors configured to detect electromagnetic radiation traversing the one or more optical guides. Example 136: one or more light sources positioned to align with the ends of one or more optical guides; and / or 136. The detection device of embodiment 135, wherein one or more optical detectors are positioned to align with the ends of one or more optical guides. Example 137: A detection device described in any one of Examples 103 to 136, wherein the processing circuit is configured to determine one or more optical properties of at least one of the functional surface and inner surface of the reaction cell arranged adjacent to one or more optical guides. Example 138: A detection device described in any one of Examples 135 to 137, wherein the processing circuit is configured to determine one or more optical properties based on determining absorption of evanescent light transmitted through one or more optical guides into the reaction cell. Example 137: further comprising a housing configured to at least partially surround the sensor chip; 137. The detection device of any one of Examples 103 and 105 to 136, wherein the housing comprises one or more holes for passage through the surrounding medium so that at least a portion of the sensor tip can contact the surrounding medium. Example 140: 140. The detection device of Example 139, further comprising one or more channels for passing surrounding medium through one or more holes in the housing of the detection device to the at least a portion of the sensor chip. Example 141: The detection device described in Example 140, further comprising one or more ventilation devices disposed in one or more channels and configured to deliver surrounding medium to at least a portion of the sensor chip through one or more holes in the housing of the detection device. Example 142: 142. The detection device of any one of Examples 103 to 141, further comprising one or more heating elements configured to heat at least a portion of the sensor tip. Example 143: 143. The detection device of Example 142, wherein the one or more heating elements are positioned adjacent to a socket of the detection device for at least partially receiving the sensor chip. Example 144: 144. The detection device of any one of Examples 103 to 143, further comprising one or more temperature sensors configured to determine a temperature of at least a portion of the sensor chip. Example 145: A detection device as described in Example 144, wherein the processing circuit is configured to control the temperature of at least a portion of the sensor chip based on determining the temperature of at least a portion of the sensor chip using one or more temperature sensors. Example 146: 146. The detection device of any one of Examples 103 to 145, further comprising one or more electrical connectors for connecting to the one or more electrical connectors of the sensor chip upon insertion of the sensor chip into the detection device. Example 147: a processing circuit is coupled to one or more electrodes of the sensor chip; and 147. The detection device of any one of Examples 103 to 146, wherein the processing circuit is configured to determine the conductivity of the substrate or composition in the reaction cell. Example 148: the processing circuitry is configured to determine one or more operating parameters indicative of the wear or remaining life of the sensor chip; and / or A detection device described in any one of Examples 103 to 147, wherein the processing circuit is configured to determine at least the usage or remaining life of the sensor chip based on determining one or more operating parameters of the sensor chip. Example 149: A detection device as described in Example 148, wherein the processing circuit is configured to determine the usage or remaining life of at least one sensor chip based on obtaining historical data indicating the usage or remaining life of the sensor chip from the sensor chip's data storage. Example 150: A detection device described in any one of Examples 148 to 149, wherein the processing circuit is configured to determine the degree of use or remaining life of at least one sensor chip based on comparing one or more determined operating parameters of the sensor chip with one or more threshold values. Example 151: A detection device described in any one of Examples 144 to 150, wherein the processing circuit is configured to determine the usage or remaining life of at least one sensor chip based on determining the type of sensor chip and / or the type of receptor protein complex used on the sensor chip. Example 152: A detection device described in any one of Examples 148 to 151, wherein the processing circuit is configured to store one or more operating parameters in the data storage of the detection device and / or in the data storage of the sensor chip. Example 153: 153. A detection device described in any one of Examples 148 to 152, wherein the processing circuit is configured to determine one or more operating parameters based on monitoring the temperature of at least a portion of the sensor chip. Example 154: 154. A detection device according to any one of Examples 103 to 153, wherein the processing circuitry is configured to determine the depletion of receptor protein complexes within the sensor chip over time. Example 155: A detection device described in any one of Examples 103 to 154, wherein the processing circuit is configured to determine the remaining life of the sensor chip based on determining the depletion of receptor protein complexes within the sensor chip over time. Example 156: the detection device includes a user interface; and A detection device described in any one of Examples 103 to 155, wherein the processing circuit is configured to provide a notification to a user via a user interface upon expiration of the sensor chip's lifespan. Example 157: the detection device includes a user interface; and A detection device described in any one of Examples 103 to 156, wherein the processing circuit is configured to provide information related to the determined one or more biologically active substances to a user via a user interface. Example 158: the detection device includes a user interface; and A detection device described in any one of Examples 103 to 157, wherein the processing circuit is configured to notify a user via a user interface when it determines that the concentration of the biologically active substance in the surrounding medium has reached or exceeded a predetermined threshold. Example 159: A detection device described in any one of Examples 156 to 158, wherein the user interface includes one or more of a vibration element, a display, one or more LEDs, and a speaker. Example 160: the sensor chip includes a chip identifier for identifying the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip; and A detection device described in any one of Examples 103 to 159, wherein the processing circuit is configured to obtain information or data from the chip identifier indicating the type of sensor chip and / or the type of receptor protein complex contained in the sensor chip. Example 161: A detection device described in any one of Examples 103 to 160, wherein the detection device includes one or more of a barcode reader, a QR code reader, and an RFID scanner. Example 162: 162. The detection device of any one of Examples 103 to 161, further comprising one or more energy storage devices for supplying electrical energy. Example 163: A detection device described in any one of Examples 103 to 162, further comprising a communication circuit that communicatively couples the detection device to a user device. Example 164: A detection device as described in Example 163, wherein the communication circuit includes a wireless communication circuit, preferably a Bluetooth transmitter. Example 165: 165. The detection device of any one of Examples 103 to 164, further comprising one or more radiation sensors for measuring exposure of the detection device to ionizing radiation. Example 166: A detection device as described in Example 165, wherein the one or more radiation sensors include at least one of a reversible photochromic layer sensitive to UV radiation and a radiochromic dye film sensitive to ionizing radiation. Example 167: 167. The detection device of any one of Examples 103 to 166, further comprising one or more of a humidity sensor, a volatile organic carbon sensor, an ozone sensor, a particulate matter sensor, a nitric acid sensor, and a carbon monoxide sensor. Example 168: Use of the detection device according to any one of Examples 103 to 167 for detecting one or more biologically active substances in a surrounding medium. Example 169: 1. A detection system for detecting one or more biologically active substances in a surrounding medium, the detection system comprising: At least one sensor chip according to any one of Examples 1 to 101; A detection system comprising the detection device according to any one of Examples 103 to 167. Example 170: 169. A method for detecting one or more biologically active substances in a surrounding medium by the detection system of Example 169, the method comprising: passing one or more biologically active substances through a membrane of the sensor chip into a reaction cell of the sensor chip; one or more biologically active substances binding to one or more receptor protein complexes, thereby inducing a change in state of at least a portion of the receptor protein complexes; detecting an induced change in state of at least a portion of the receptor protein complex with a detection device; and generating a detection signal indicative of the presence of one or more biologically active substances in the surrounding medium based on the determined change in state of at least a portion of the receptor protein complex. Example 172: 171. The method of Example 170, wherein passing the one or more biologically active substances through the membrane of the sensor chip comprises contacting the membrane of the sensor chip with a surrounding medium. Example 172: 172. The method of any one of Examples 170 to 171, further comprising activating the sensor chip in response to supplying deionized water from a reservoir of the sensor chip to a reaction cell of the sensor chip. Example 173: 173. The method of Example 172, wherein activating the sensor chip comprises unblocking fluid communication between the at least one reservoir and the reaction cell of the sensor chip using at least one blocking element between the at least one reservoir and the reaction cell. Example 174: the at least one blocking element comprises a water-impermeable membrane disposed between the reservoir and the reaction cell; 174. The method of example 173, wherein activating the sensor chip comprises disrupting at least a portion of the water-impermeable membrane. Example 175: the at least one blocking element comprises a movable pin disposed between the reservoir and the reaction cell; 175. The method of any one of Examples 173 to 174, wherein activating the sensor chip comprises moving a movable pin. Example 176: 176. The method of any one of Examples 173 to 175, wherein activating the sensor chip comprises removing the sealing cover from the outer surface of the membrane. Example 177: The method of any one of Examples 170 to 176, wherein detecting the induced state change includes determining one or more of the number, mass, density, and mass density of receptor protein complexes dissolved in the substrate of the reaction cell of at least one sensor chip. Example 178: The method of any one of Examples 170 to 177, wherein detecting the induced state change includes determining one or more of the number, mass, density, and mass density of receptor protein complexes immobilized on at least one functional surface of the reaction cell or released from at least one functional surface of the reaction cell. Example 179: The method of any one of Examples 170 to 178, wherein detecting the induced state includes determining one or more of the number, mass, density, and mass density of receptor protein complexes immobilized on or released from at least one inner surface of the reaction cell arranged toward at least one functional surface of the reaction cell. Example 180: The method of any one of Examples 170 to 179, wherein detecting the induced state change comprises exciting one or more fluorescent labels of the receptor protein complex and detecting fluorescent light emitted by the one or more fluorescent labels. Example 181: 181. The method of any one of Examples 170 to 180, wherein detecting the induced state change comprises detecting light scattered by one or more components of a receptor protein complex within the reaction cell. Example 182: 182. The method of any one of Examples 170 to 181, wherein detecting the induced state change comprises determining one or more optical properties of at least one of the functional surface and the interior surface of the reaction cell. Example 183: 183. The method of any one of Examples 170 to 182, wherein detecting the induced state change comprises determining absorption of evanescent light transmitted into the reaction cell through one or more optical guides of the sensor chip.

[0195] The embodiments will now be further described with reference to the following figures: [Brief explanation of the drawings]

[0196] [Figure 1A] FIG. 1A shows a perspective view of a sensor chip for detecting one or more bioactive substances. [Figure 1B] 1B, 1C and 1D each show a cross-sectional view of the sensor chip of FIG. 1A. [Figure 1C] Same as above. [Figure 1D] Same as above. [Figure 2] Figure 2A shows a perspective view of a detection system for detecting one or more biologically active substances, Figure 2B shows a cross-sectional view of the detection system of Figure 2A, and Figure 2C shows another cross-sectional view of the detection system of Figure 2A. [Figure 3] 3A to 3C each show a cross-sectional view of a reaction cell of a sensor chip. [Figure 4] Figure 4A shows a perspective view of a sensor chip for detecting one or more bioactive substances, and Figures 4B and 4C each show a cross-sectional view of the sensor chip of Figure 4A. [Figure 5] FIG. 5 shows a cross-sectional view of a detection system for detecting one or more biologically active substances. [Figure 6] FIG. 6 shows a cross-sectional view of the reaction cell of the sensor chip. [Figure 7] FIG. 7 shows a flow chart illustrating a method for detecting one or more biologically active substances in a surrounding medium. DETAILED DESCRIPTION OF THE INVENTION

[0197] 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.

[0198] Figure 1A shows a perspective view of a sensor chip 100 for detecting one or more biologically active substances. Figures 1B, 1C and 1D show cross-sectional views of the sensor chip 100 of Figure 1A.

[0199] The sensor chip 100 shown in FIGS. 1A-1D is illustratively shown or designed as an elongated structure having a rectangular cross section, for example, in projection parallel to the longitudinal axis 180 of the sensor chip 100.

[0200] The sensor chip 100 comprises a housing 181 or outer housing 181 that surrounds the reaction cell 101. The sensor chip 100 further comprises an open grating 113 beneath which is disposed a membrane 114 that separates the reaction cell 101 from a surrounding medium, such as air or water. The reaction cell 101 includes a receptor protein complex 115 that is configured to bind to one or more biologically active substances within the reaction cell 101, thereby inducing a detectable state change in at least a portion of the receptor protein complex 115, as described hereinabove and in more detail hereinbelow.

[0201] Optionally, the sensor chip 100 includes a reservoir 102 or a water reservoir 102, which may be integrally formed with a housing 181. Thus, the portion of the housing 181 forming the water reservoir 102 may be made of only one type of single material, while the portion of the housing 181 in which the reaction cell 101 is disposed may be divided into multiple parts or portions. In particular, the sensor chip 100 or its housing 181 includes a lower light-transmitting portion 103 or detection window 103, two parts 104 adjacent to the light-transmitting portion 103, a rectangular part 105 facing the reservoir 102, another rectangular wall 106 disposed on the opposite side thereof, and a flat rectangular part 107 on the upper side. The upper rectangular part 107 includes an open grating 113.

[0202] The light transmitting portion 103 or the detection window 103 of the sensor chip 100 is configured to transmit light at a specific wavelength λ em light of a specific wavelength λ, for example the emission wavelength of fluorescent radiation, but ex The optical filter may be made of a material that does not need to be transparent to light at the excitation wavelength, for example for fluorescence excitation.

[0203] The housing parts 104, 105 and 106 are not transparent to light and may optionally be coated on the side facing the internal volume of the reaction cell 101 with a material with low protein adsorption, such as a fluoropolymer.

[0204] The part 105 of the housing 181 provides an opening 108 which can be a channel 109 , for example a flexible microchannel 109 .

[0205] The component 106 of the housing 181 is configured to emit light at a particular wavelength λ, such as the excitation wavelength for fluorescence excitation. ex The optical connector or opening 110 may be sealed with a material transparent to the light.

[0206] The opening 110 or optical connector 110 is preferably shaped so that light passing therethrough produces a sheath of light 111 that spans the width of the reaction cell 101. The optical connector 110 or opening 110 is preferably positioned such that the sheath of light 111 is located in close proximity to the gas permeable membrane 114, preferably within a distance of 0.1 mm or less.

[0207] The side piece 104 of the housing 181 provides one or more surface features 112, such as guides 112, that allow the sensor chip 100 to be attached to a detection device and ensure proper orientation and positioning.

[0208] The flat rectangular part 107 of the housing 181 is provided with an open grating 113, for example having a mesh size in the range of about 0.2 to 2 mm. Directly below the grating 113, preferably fused to the grating 113, a gas-permeable membrane 114 is positioned such that the membrane 114 is protected.

[0209] The membrane 114 has little thickness, low diffusion resistance, and low protein adsorption. The inside of the permeable membrane 114 directly faces the internal volume of the reaction cell 101.

[0210] When the sensor chip 100 is not installed in the detection device, the open grid 113 can be covered and hermetically sealed by a removable sealing cover (not shown), such as foil. When the sensor chip 100 is again removed from the detection device, for example because the sensor chip 100 is temporarily not in use or because the user intends to change the type of sensor chip 100, for example to focus on another aspect of environmental quality, the sealing cover can be reinstalled over the grid 113, thereby preventing water from evaporating from the reaction cell 101 and consuming the receptor-protein complexes 115.

[0211] Within the reaction cell 101, the receptor protein complex 115 is immobilized on a gas permeable membrane 114. The receptor protein complex 115 may be immobilized specifically on a functional surface 182 of the reaction cell 101, which in the embodiment of Figures 1A-1D is defined by the inner surface of the membrane 114 facing the interior of the reaction cell 101.

[0212] Immobilization of the receptor protein complex on the functional surface 182 or inner surface of the membrane 114 can be achieved by covalently binding molecules that are known low affinity ligands of the receptor protein complex 115 .

[0213] The reaction cell 101 may contain a substrate 116, which is preferably lyophilized, such as a mixture 116 of salts, buffers and optionally proteins that stabilize the receptor protein complex 115, and / or small amounts of surfactant molecules such as Tween or Triton X-100.

[0214] The optically transparent wall 103 or the detection window 103 can be optionally coated with covalently bound molecules or molecular capture complexes 117 that are known to be high-affinity ligands for the receptor protein complex 115 or to bind portions of the receptor protein complex 115 with high affinity. These molecular capture complexes 117 can act as a sink for free receptor protein complexes 115 or portions thereof and can reduce the occurrence of multiple signals generated by the same free receptor protein complex 115. The molecular capture complexes 117 can be covalently bound to an inner surface 183 of the reaction cell 101, which is disposed toward the functional surface 182 or membrane 114. In the example of FIGS. 1A-1D, the inner surface 183 of the reaction cell 101 is disposed opposite the functional surface 182 and / or membrane 114.

[0215] The molecules or cross-linkers that bind the molecular capture complexes 117 to the inner surface of the detection window 103 are coupled to a specific or predetermined wavelength λ em Furthermore, the light may not absorb light of a predetermined wavelength λ, for example, the emission wavelength of fluorescent radiation. emA molecule known to quench the fluorescence of may be covalently attached to the inner surface (not shown) of the detection window 103 .

[0216] The water reservoir 102 may have an adjustable volume. For example, the reservoir 102 may include or be defined by a flexible blister 118 containing deionized water. The flexible blister 118 is connected to the reaction cell 101 via a channel 109, such as a flexible microchannel 109 having a diameter of 0.1 to 0.5 mm. The channel 109 is essentially an extension of the blister 118 and reaches through the opening 108. The portion of the housing 181 in which the flexible blister 118 is contained includes one or several small holes 119 or openings 119 that allow air or ambient medium to enter the chamber or reservoir 102 and allow water to flow out of the blister 118 without creating negative pressure within the chamber or reservoir 102.

[0217] The channel 109 can be blocked by a blocking element 120, for example a movable or removable pin 120. Furthermore, the reaction cell 101 and the deionized water are separated by a semipermeable membrane 121, for example at the end of the channel 109 directly facing the reaction cell 101, which prevents mixing of the water in the blister 118 with the buffered isotonic solution in the reaction cell 101 in the absence of the removable pin 120.

[0218] In a virgin state of the sensor chip 100, the deionized water contained in the flexible blister 118 is preferably stored at an overpressure relative to the surroundings. Specifically, in a virgin state of the chip 100, the flexible blister 118 is slightly expanded so that it can actively push an initial amount of deionized water into the reaction cell 101 when the channel 109 opens to the reaction cell 101.

[0219] On the side facing the reaction cell 101, part 105 of the housing 180 of the sensor chip 100 comprises an electrode 122 that allows measuring the conductivity of the deionized water in which the substrate 116 or matrix 116 inside the reaction cell 101 is dissolved. Conductivity measurements can provide an effective means for monitoring the osmolality of the solution present in the reaction cell 101, which can be an indicator of whether the protein complexes 115 are in their native functional state.

[0220] Figure 2A shows a perspective view of a detection system 500 for detecting one or more biologically active substances. Figures 2B and 2C each show a cross-sectional view of the detection system 500 of Figure 2A. In particular, Figures 2A-2C show the detection system 500 having a detection device 200 and a sensor chip 100 inserted into the detection device 200. Unless otherwise noted, the sensor chip 100 of Figures 2A-2C has the same features as the sensor chip 100 described with reference to Figures 1A-1D.

[0221] 2A-2C show detection device 200 with sensor chip 100 installed, bonded, or attached. Detection device 200 includes a socket 202 into which sensor chip 100 can be axially inserted. Socket 202 includes surface features 203, such as guides 203, that ensure proper orientation and positioning of sensor chip 100, and optionally, a sensor (not shown) that detects whether sensor chip 100 is inserted and whether sensor chip 100 is properly oriented. The sensor can shut down detection device 200 if no chip is inserted or if the chip is improperly inserted.

[0222] Once inserted, the sensor chip 100 is held in place by a click mechanism 204, e.g., by a hook that is pushed by a spring towards the sensor chip 100. Mechanisms such as a magnetic connection may alternatively or additionally be used.

[0223] The detection device 200 further provides a light source 205, for example a laser diode, which emits light at a particular wavelength λ when the device 200 is activated. ex light, or a range of fluorescence excitation wavelengths, λ ex The light source 205 is attached to the housing 206 of the detection device 200 and is positioned to emit light into the reaction cell 101 of the sensor chip 100 through the optical connector 110 or opening 110 of the sensor chip 100.

[0224] The detection device 200 further provides one or more sensors 207 for detecting a state change induced by binding of the receptor protein complex 115 with one or more biologically active substances within the reaction cell 101 .

[0225] 2A-2C, the detection device 200 includes one or more optical sensors 207, for example an array of optical sensors 207, which are positioned under the light-transmitting portion 103 or detection window 103 of the sensor chip 100 and optionally receive light at a particular wavelength λ em The optical fiber 202 is protected by a layer 208 of material that is transparent to light of a range of wavelengths, such as light of a wavelength of 100 keV or a range of fluorescent emission wavelengths.

[0226] The detection device 200 further includes a processing circuit 209 coupled to the at least one sensor 207, the processing circuit 209 being configured to provide a detection signal indicative of the presence of one or more biologically active substances in the surrounding medium based on determining a change in the state of at least a portion of the receptor protein complex 115 in the reaction cell 101.

[0227] The processing circuitry 209 and / or the detection device 200 may include a processor, memory, data storage, communication circuitry, a Bluetooth receiver and / or transmitter, or other electronic components.

[0228] The detection device 200 further comprises a heating element 210 that heats at least a portion of the sensor chip 100. The heating element 210 can be located below the sensor chip 100, for example below one or more sensors 207, or at some other location where the temperature of the reaction cell can be controlled. The detection device 200 can also include one or more temperature sensors for temperature control.

[0229] A channel 211 is formed within the housing of the detection device 200 and extends along the face of the sensor chip 100 where the open grating 113 is located. The channel 211 communicates with the ambient environment by ventilation holes 212 or openings 212. Airflow through the channel 211 may optionally be driven by a ventilation device 213, such as a micro-ventilator 213.

[0230] Additionally, the detection device 200 may provide one or more of an on / off button 214, a speaker 215, a connection 216 for charging a battery, one or more batteries, a means 217 for securing the device, such as to a backpack strap, and an array of diodes 218 for indicating the status of the device 200 and / or the sensor chip 100. The indication of the status of the device 200 and / or the sensor chip 100 may include, but is not limited to, the battery status of the device 200, the conductivity of the aqueous solution or substrate 116 present in the reaction chamber of the sensor chip 100, the degree of use of the device 200 or the sensor chip 100, the remaining life of the sensor chip 100, the predicted depletion of the receptor protein complex 115, or others.

[0231] Furthermore, the detection device 200 comprises a user interface 219, for example a small screen 219 that provides information about the instantaneous and current air quality. In addition, other information may also be displayed.

[0232] The operating principles and operation of the detection system 500, detection device 200 and / or sensor chip 100 of FIGS. 1A-2C are summarized below.

[0233] The sensor chip 100 can be removed from its packaging (not shown) and the blocking element 120 or pin 120 and sealing cover (not shown) removed to activate the sensor chip 100. When the pin 120 is removed, the channel 109 accessed through the opening 108 is opened, allowing water from the reservoir 102 to reach the semipermeable membrane 121 and ultimately the reaction cell 101, which contains a preferably lyophilized substrate 116 containing salts, buffers, and optionally a protein that stabilizes the receptor-protein complex 115 and optionally a small amount of surfactant molecules. The osmolarity of the resulting solution will draw water from the reservoir 102 or blister 118 into the reaction cell 101 until the reaction cell 101 is completely filled and the osmotic pressure is counteracted by the rigid housing of the reaction cell 101 or sensor chip 100.

[0234] The sensor chip 100 can then be inserted into the detection device 200 and secured with the click mechanism 204 present in the device 200, and the device 200 can be activated. Once secured in the detection device 200, contact is established between the electrodes 122 present in the chip 100 and corresponding connections disposed within the detection device 200, and the optical connectors 110 or openings 110 present in the wall of the chip 100 are positioned in front of the light source 205 of the detection device 200. Optionally, the heating element 210 can be activated. Once the sensor chip 100 has reached its operating condition, e.g., a target osmolality and a target minimum temperature within the reaction cell 101, the ventilation device 213 and light source 205 can be activated either automatically or by the user, e.g., via an application installed on a user device that can be wirelessly coupled to the detection device 200.

[0235] A ventilator 213 collects ambient air and pushes it through the open grid 113 of the sensor chip 100 and channels 211 in which the gas permeable membrane 114 is located. Molecules and bioactive substances present in the ambient air will diffuse across the membrane 114 and elicit a sensor response, as described above and with reference to Figures 3A-3C.

[0236] 3A to 3C each show a cross-sectional view of a reaction cell 101 of the sensor chip 100 to illustrate a possible operating principle of the sensor chip 100. FIG.

[0237] The receptor protein complex 115 is immobilized on the functional surface 182 of the reaction cell, such as on the inner surface of the gas permeable membrane 114, by a low affinity ligand 301 covalently bound to the gas permeable membrane 114. The receptor protein complex 115 comprises at least one ligand binding domain 302 of a receptor protein configured to bind to one or more bioactive substances entering the reaction cell 101. The receptor protein complex 115 further comprises at least one fluorescent label 303, hereinafter also referred to as a fluorophore, and an affinity tag 304.

[0238] The receptor protein complex 115 or the ligand binding domain 302 of the receptor protein can be the full-length receptor protein or only one or a few domains of the receptor protein, such as only the ligand binding domain 302. The receptor protein complex 115 or the ligand binding domain 302 can include, for example, a human heterologous sensor, a hormone receptor protein, or an aryl hydrocarbon receptor.

[0239] Fluorophore 303 can be, for example, green fluorescent protein, in which case receptor protein complex 115 is a fusion protein or covalently attached fluorescent dye, such as DAPI (4,6-diamidino-2-phenylindole).

[0240] The affinity tag 304 has a high affinity for a component 305 of a coating present on the light-transmitting wall 103 or the detection window 103. The component 305 refers to or represents the molecular capture complex 117 described with reference to Figures 1A-1D. The affinity tag 304 can be, for example, biotin, in which case the coating on the light-transmitting wall 103 or the detection window 103 of the reaction cell 101 would include streptavidin. Alternatively, the affinity tag 304 can be a histidine tag, in which case the coating on the light-transmitting wall 103 of the reaction cell 101 would include a chelated nickel ion.

[0241] The composition of the receptor protein complex 115 can be custom-tuned for a given spectrum of detected environmental bioactive substances and a target sensitivity. For example, multiple fluorophores 303 can be present in a single receptor protein complex 115, i.e., different fluorophores and / or several units of the same fluorophore can be linked to the same receptor protein complex 115. Furthermore, more than one type of receptor protein complex 115 can be present in a given sensor chip 100. For example, different receptor proteins and / or different domains of the same receptor protein, and / or receptor proteins with different recombinant properties, e.g., carrying different fluorophores, and / or receptor protein complexes with different compositions can be used.

[0242] The biologically active agent 307 or molecule 307 that is the ligand for the receptor protein complex 115 will diffuse through the gas permeable membrane 114 and, once in solution within the reaction cell 101, will compete with the low affinity ligand 301 covalently bound to the gas permeable membrane 114. This competitive binding will release the receptor protein complex 115 from the membrane 114 with a certain probability, depending on the relative affinities of the low affinity ligand 301 and the biologically active agent 307. The released receptor protein complex 308 in Figure 3B is free to diffuse within the reaction cell 101.

[0243] The light source 205 present in the detection device 200 emits light of wavelength λ ex emitting a beam or preferably a sheath of light 309 into the reaction chamber, ex is the excitation wavelength of the fluorophore 303 present in the receptor protein complex 115. When free receptor protein complex 308 diffuses into the light path, the fluorophore 303 is excited and emitted at wavelength λ as shown in FIG. em emits fluorescent light.

[0244] The light-transmitting wall 103 or detection window 103 of the sensor chip 100, and optionally the wall 208 separating the photodetector 207 from the sensor chip 100, is irradiated at wavelength λ em Due to the geometry of the reaction cell 101 and the position of the optical sheath 309, approximately half of the light emitted by the fluorophore 303 reaches the sheath of the optical sensor 207 surrounding the reaction cell (the other half travels towards the non-permeable wall of the reaction cell or towards the gas permeable membrane and is not detected).

[0245] Depending on the bandwidth of the optical sensor 207, the wavelength λ that may be scattered by proteins or particulate impurities in the liquid matrix or substrate 116 in the reaction cell 101 may be ex To avoid this, the detection window 103 of the reaction cell 101 is designed to have a wavelength λ ex Preferably, the film is opaque to light.

[0246] Because diffusional movement is random, the receptor protein complexes 115 may remain in the light path or leave and re-enter the light path, resulting in several signals over time. After prolonged operation or extensive exposure of the sensor chip 100, most of the receptor protein complexes 115 may become detached from the gas-permeable membrane 114, which may impair proper detection of further fluorescence. Therefore, the light-transmitting wall 103 or detection window 103 of the reaction cell 101 acts as a sink for the receptor protein complexes 115 because they are coated with molecular capture complexes 117, 305 that bind with high affinity to the affinity tags 304 on the receptor protein complexes 115.

[0247] All inner surfaces of the reaction cell 101, except for the light-transmitting wall 103 or detection window 103, can be covered with a low protein-adsorption coating, and due to this inner shape of the reaction cell 101, most of the released receptor-protein complexes 115 will eventually pass through the light path and reach the light-transmitting part 103 or detection window 103 of the cell 101, where they will be removed from the solution.

[0248] An operating parameter, such as the mean residence time of the receptor protein complex 115 in solution or its half-life, can be calculated based on the mass and size of the receptor protein complex 115, the viscosity of the solution in the reaction cell, and the temperature within the cell 101. This mean residence time can be used to correct the detection signal reported by the detection device 200 for multiple excitation and emission events, thereby increasing the sensitivity and accuracy of the detection device 200.

[0249] For example, when scattered by proteins or small particulate impurities present in the solution in the cell, the wavelength λ exThis scattered light can reach the immobilized receptor protein complex 115 present in the gas permeable membrane 114 or the detection window 103 of the reaction cell, which has been liberated by the biologically active substance 307 entering the reaction cell 101 and diffusing across the cell 101. This scattered light excites the fluorophore 303 of the receptor protein complex 115 and emits light of wavelength λ em This induces the emission of photons of light that reach the photodetector 207, thereby generating a signal unrelated to the immediate presence of air contamination. Accordingly, the coating on the light-transmitting wall 103 or detection window 103 of the reaction cell 101 and / or on the gas-permeable membrane 114 may contain molecules known to quench the fluorescence of the fluorophore 303 by donating or accepting electrons (not shown). Quenching the scattered light reduces and / or eliminates these extraneous excitation events, thereby reducing and / or eliminating noise from light scattering. Alternatively, the fluorescence intensity detected by the light sensor 207 may be corrected for scattering effects. For example, the fluorescence intensity from receptor proteins trapped in the light-transmitting wall 103 or gas-permeable membrane 114 can be predicted based on the empirically determined amount of scattered light reaching them, the stability of the fluorophore 303, and the amount of receptor protein complex 115 expected to be present therein, which can be determined, for example, from the cumulative fluorescence signal detected by the light sensor 207.

[0250] Figure 4A shows a perspective view of a sensor chip 400 for detecting one or more biologically active substances. Figures 4B and 4C each show a cross-sectional view of the sensor chip 400 of Figure 4A. Unless otherwise noted, the sensor chip 100 of Figures 4A and 4B has similar features to the sensor chip 100 described with reference to any of Figures 1A-3C.

[0251] The sensor chip 400 of Figures 4A-4C is a double-layer structure with a cylindrical cross-section. Other cross-sections are possible, such as a rectangular cross-section. The outer layer of this structure or sensor chip 400 comprises a rigid open lattice 401 through which ambient air can enter through an air chamber 402. The air chamber 402 is functionally similar to the air channel 211 described above.

[0252] The inner layer of the structure of sensor chip 400 comprises an open lattice 403 through which components present in the air in air chamber 402 can reach gas permeable membrane 404. The inner open lattice 403 and gas permeable membrane 404 are functionally similar to the open lattice 113 and gas permeable membrane 114 described above.

[0253] The volume enclosed within the cylinder formed by gas permeable membrane 404 defines reaction cell 405 of sensor chip 400, which is functionally similar to reaction cell 101 described above.

[0254] Similar to the exemplary embodiment of sensor chip 100 described above, the interior surface of gas permeable membrane 404 is covered with immobilized receptor protein complexes (not shown in FIGS. 4A-4C).

[0255] Within the reaction cell 405, one, two or multiple optical guides 406 are arranged. These may be in the form of fibers or in the form of planar optical guides or any other suitable shape.

[0256] The optical guide 406 may be coated with a covalently bound molecular capture complex (not shown in FIG. 4) that has been shown to bind with high affinity one or several components of the receptor protein complex 115. The distance between the gas permeable membrane 404 and the surface of the optical guide 406 is preferably in the range of 0.1 mm or less.

[0257] The chemical nature, biological origin, and means of immobilization of the molecule or molecular complex on the optical guide 406 are similar to those described for the molecule or molecular complex 117 covalently bound to the light-transmitting wall 103 of the reaction cell 101 described with reference to the previous figures.

[0258] Alternatively, the arrangement of the immobilized receptor protein and high affinity complex may be reversed, i.e., the receptor protein may be immobilized on the optical guide 406 and the high affinity complex may be immobilized on the gas permeable membrane 404.

[0259] Preferably, the absorption spectrum and other optical properties of the immobilized molecule or molecular complex, and the absorption spectrum of the covalent bond, do not overlap, or overlap only to a limited extent, with the absorption spectrum or other optical properties of the receptor protein complex 115.

[0260] One end 407 of the sensor chip comprises a water reservoir 408 that is functionally similar to the water reservoir 102 described above. The connection of the water reservoir 408 to the reaction cell 405 and the operating principle of the water reservoir 408 can be the same as described above. A blocking element 409 or removable pin 409 can seal a flexible blister 410 disposed within or defining the reservoir 408 from the lyophilized contents (not shown) of the reaction cell 405. A semipermeable membrane 411 separates the substrate present in the reaction cell 405 from freely mixing with the water in the blister 410 once the pin 409 is removed.

[0261] Additionally, this end of the sensor chip 400 may provide a reflective element, for example an optical mirror, or an optical guide 412 that can reflect light passing through a single optical guide 406 and / or connect a pair of two optical guides 406.

[0262] The other end of the sensor chip 400 comprises a structure 413 or component 413 having one, two or multiple optical connectors 414 or openings 414 that align with and form an extension of an optical guide 406 disposed within a reaction cell 405 of the chip 400.

[0263] Additionally, portions of the structure 413 or components 413 of the sensor chip 400 include electrical contacts or connectors 415 that electrically connect the chip 400 to a detection device when inserted therein. These contacts 415 are functionally similar to the electrical contacts 122 described above.

[0264] In operation, i.e., when attached to an activated detector, light 416 emitted by the detector optics, e.g., by one or more light sources, passes longitudinally through the optical guide 406 spanning the reaction cell 405 along the longitudinal axis of the chip 400 from one end of the chip 400 to the other end of the chip 400. The light is reflected or deflected by the reflective element 412 or optical structure 412 and travels back through the optical guide 406 toward the end or portion 413 of the sensor chip 400, as indicated by reference numeral 417 in FIG. 4B, and finally leaves the chip 400 toward the detector optics.

[0265] Figure 5 shows a cross-sectional view of a detection system 500 for detecting one or more biologically active substances. In particular, Figure 5 shows detection system 500 having a detection device 550 and a sensor chip 400 inserted into detection device 550. Unless otherwise noted, sensor chip 400 of Figure 5 has the same features as sensor chips 100, 400 described with reference to Figures 1A-4C. Similarly, detection device 550 of Figure 5 has the same features as detection device 200 described with reference to Figures 2A-4C.

[0266] 5 shows the sensor chip 400 inserted into a detection device 550. A structure 413 forming one end of the sensor chip 400 plugs into the detection device 550 and establishes contact with electrical and optical connections disposed within the device 550. Specifically, the optical guides 406 present within the sensor chip 400 connect via optical connectors 414 or openings 414 to an optical system 503 disposed within the detection device 550. The optical system 503 comprises one or several light sources 504 and one or several light detectors 505, such as light sensors 505.

[0267] The socket present in device 550 and end structures of tip 400, as described above, provide complementary guides (not shown) that ensure proper orientation of tip 400 within device 550. Fixation of tip 400 within the socket can be achieved, for example, by a click-in mechanism, a magnetic connection, or screw tightening.

[0268] Additionally, device 550 includes a battery, a microprocessor, and possibly other electronic components as described with reference to the previous figures.

[0269] Ambient air passively enters the air chamber 402 through the rigid open lattice 401 of the sensor chip 400. The driving force can be the movement and / or Brownian motion of the ambient air relative to the sensor chip 400.

[0270] Alternatively, the socket of the device 550 may be the same length as or longer than the complete sensor chip 400. In this case, the chip 400 is fully inserted into the device 550, which may include additional features such as a vent to sample ambient air and supply it to the air chamber 402 of the sensor chip 500.

[0271] The features present on the surface of device 550, such as the diode, screen, or means for securing the device to clothing, a bicycle, or a backpack strap, are similar to those described with reference to Figures 2A-2C.

[0272] FIG. 6 shows a cross-sectional view of a reaction cell 405 of the sensor chip 400 illustrating a possible operating principle of the sensor chip 400 of FIGS.

[0273] Similar to the example described with reference to Figures 1A-3C, the receptor protein complex 115 is immobilized on the gas permeable membrane 404 by binding to a covalently attached molecule 301 known to be a low affinity ligand for the ligand binding domain 302 of the receptor protein complex 115 being used.

[0274] The receptor protein complex 115 consists of at least the ligand binding domain 302 of the receptor protein. Optionally, further components are present, such as an affinity tag 304. The characteristics of the components of the receptor protein complex 115, such as their biological origin or recombinant nature, are as described above with reference to the preceding figures.

[0275] Environmental molecules or bioactive substances 307 present within the air chamber 402 diffuse through the open grating 403 and gas permeable membrane 404 and into the reaction cell 405 .

[0276] Once inside the reaction cell 405 , the bioactive agent 307 competes for binding at the ligand binding domain 302 of the receptor protein complex 115 and ultimately releases the receptor protein complex 115 from the membrane 404 .

[0277] The released receptor protein complex 308 moves freely within the reaction cell 405 and eventually reaches the optical guide 406 at its center, where it binds to molecules or molecular capture complexes 117 present on the surface of the optical guide 406. This binding changes the properties of the boundary layer between the substrate or liquid matrix present in the reaction cell 405 and the surface of the optical guide 406.

[0278] Light 611 passing through optical guide 406 is not completely confined to optical guide 406, but rather penetrates to some extent into the substrate or liquid matrix present in reaction cell 405, creating an evanescent field that interacts with the immediate surroundings of optical guide 406.

[0279] For example, the detector 550 or one or more sensors 505 can measure the absorption of the evanescent field. em The absorption spectrum of one or more components of the receptor protein complex 115 may be in the wavelength range λ abs The maximum value is shown by λ. abs ≒λ em If so, the presence of receptor protein complexes 115 near the surface of the optical guide 406 results in a decrease in the light intensity reaching the optical sensor 505 in the sensor device 550. This decrease in light intensity can be quantified. This decrease per unit time provides a direct measure of the number of receptor protein complexes 115 binding to the optical guide 406 per unit time, which in turn correlates with the amount of bioactive substances 307 entering the reaction cell 405 and therefore their concentration in the ambient air. In alternative embodiments, waveguide coupling, surface plasmon resonance, or fluorescence excitation of components of receptor protein complexes 115 by, for example, evanescent fields, can be employed.

[0280] Alternatively, the detection principle may be reversed. The receptor protein complex 115 may be immobilized on the optical guide 406 and released from the optical guide upon binding of a biologically active substance that enters the reaction cell 405 from the surrounding environment. The presence of a ligand for the receptor protein complex 115 reduces the interaction between the complex 115 and the evanescent field in this embodiment. For example, the presence of a ligand for the receptor protein complex 115 in the surrounding environment reduces the absorption of evanescent light, thus increasing the light intensity reaching the photodetector 505 in the detection device 550.

[0281] Yet another detection principle that may be used in the sensor chip 400 relies on the piezoelectric detection of the deposition and / or release of receptor protein complexes. This operating principle may be identical to that described with reference to Figure 6, but detection of the binding of free receptor protein complexes 115 to high affinity ligands on the receptor surface is achieved by determining the mass of material bound to the surface instead of a change in the optical properties of the surface.

[0282] In such an embodiment, the optical guide 406 can be replaced by one or more piezoelectric elements capable of detecting changes in mass adsorbed on its surface with high sensitivity, whereby at least one piezoelectric element can be present in the center of the reaction cell 405 or can include one or several of the walls of the reaction cell.

[0283] Alternatively, a piezo-based sensor chip may rely on the opposite principle: the receptor-protein complex 115 can be immobilized on a piezoelectric element and released therefrom upon binding to a bioactive substance that enters the reaction cell 405. The result is the detection of a decrease in the mass bound to the piezoelectric element.

[0284] While sensors for detecting environmental agents using piezoelectric elements have been described, the solution proposed herein offers significantly higher sensitivity as follows: Piezo-based sensors described in the art rely on measuring the mass increase caused by binding of environmental agents to receptor proteins immobilized on the surface of a piezoelectric element, for example. In contrast, the indirect detection methods described herein rely on binding of intact receptor protein complexes 115, which typically have orders of magnitude larger mass and can therefore be more efficiently detected by piezoelectric elements.

[0285] Below, exemplary materials for the sensor chip are described, but are not to be construed as being limiting. The inner surface of the reaction cell, including the gas-permeable membrane, may be coated or fabricated with a material that is non-absorbent to (water-soluble) proteins. Examples include fluoropolymers such as Teflon, or highly hydrophobic coatings. Alternatively, a surface pre-coating with a protein such as ovalbumin or bovine serum albumin can be provided. The opening through which light emitted by the light source enters the reaction cell should be at least λ ex The material may be transparent to light.

[0286] Suitable materials for the gas-permeable membrane can include, but are not limited to, hydrophobic membranes with micron-sized perforations made from, for example, fluoropolymers, porous PET membranes, carbon paper, preferably with a hydrophobic coating, and porous silicon-PDMS membranes.

[0287] The material of the detection window or light-transmitting wall of the reaction cell is em and preferably has a wavelength λ exThe corresponding materials are known for use in spectroscopic instruments and are specific for the fluorophores used in the reaction cell. The material of the detection window or the light-transmitting wall of the reaction cell may additionally be resistant to aqueous salt solutions at neutral pH. If such materials with additional spectroscopic properties are not available, coated or double-layered walls can be used. The coating or protective layer may be a protective layer for the wavelength λ em To increase the robustness of the detection window, a sandwich structure can be used, i.e., the window can be transparent to light with a wavelength λ em is transparent to light of wavelength λ ex For example, a material that is opaque to at least the wavelength λ em Alternatively, the light source may be placed between two layers of rigid material that are transparent to light of at least wavelength λ. em A robust material that is transparent to light of wavelength λ em It is transparent to light of wavelength λ ex The light may be coated with a suitable coating that is opaque to the light.

[0288] The optical system of the detector is, as mentioned above, ex or λ abs and the opening in the wall of the reaction cell may be transparent to light at least in this wavelength range. Alternatively, the light source may emit light over a wide range of wavelengths, in which case the opening in the wall of the reaction cell may preferably be transparent to light within a narrow band of wavelengths within the range of λ ex or λ abs It is transparent to only a narrow bandwidth of light within the range

[0289] For the optical guide, the material should be of a suitable refractive index compared to the substrate or liquid matrix inside the reaction cell to optimize the strength of the evanescent field, the exact value depending on the wavelength used, which in turn depends on the absorption spectrum of the receptor-protein complex.

[0290] For the detection device, one or more layers may be used to cover and protect the sensor, such as the optical sensor, with the same requirements and technical solutions as described for the light-transmitting wall or detection window herein above.

[0291] The following summarizes exemplary, non-limiting dimensions of the detection device and sensor chip.

[0292] For devices in stationary use, the detector has a maximum range of approximately 1000 cm 3 The sensor chip may be approximately 1-10 cm long, 5-10 cm wide, and 2-3 cm thick, and the reaction cell may preferably have a diffusion distance of less than 0.5 mm.

[0293] For portable detection devices, the detection device should be approximately 200 cm 3 The sensor chip may be approximately 1 to 5 cm in length, 0.5 to 1 cm in width, and 0.5 to 1 cm in thickness, and the reaction cell may preferably have a diffusion distance of less than 0.5 mm.

[0294] FIG. 7 shows a flow chart illustrating a method for detecting one or more biologically active substances in a surrounding medium using, for example, the detection systems, detection devices and / or sensor chips described with reference to the previous figures.

[0295] In step S1, one or more biologically active substances pass through the membrane 114 of the sensor chip 100 into the reaction cell 101 of the sensor chip 100.

[0296] In step S2, one or more biologically active substances bind to one or more receptor protein complexes 115, thereby inducing a change in state of at least a portion of the receptor protein complexes 115.

[0297] In step S3, the induced change in state of at least a portion of the receptor protein complex 115 is detected.

[0298] In step S4, a detection signal is generated based on the determined change in state of at least a portion of the receptor protein complex 115, the detection signal being indicative of the presence of one or more biologically active substances in the surrounding medium.

[0299] For purposes of this specification and the appended claims, unless otherwise indicated, all numbers expressing amounts, quantities, percentages, and the like are to be understood in all instances as modified by the term "about." Also, all ranges are inclusive of the disclosed maximum and minimum points, and include all intermediate ranges therein, which may or may not be specifically recited herein. Thus, in this context, the number A is to be understood as A ± 20% of A. Within this context, the number A may be considered to include values that fall within the normal standard error for the measurement of the property for which the number A varies. In some cases, such as those used in the appended claims, the number A may deviate by the percentages recited above, provided that the amount by which A deviates does not materially affect the basic and novel characteristics of the claimed invention. Also, all ranges are inclusive of the disclosed maximum and minimum points, and include all intermediate ranges therein, which may or may not be specifically recited herein.

[0300] 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 practice of the invention, from a study of the drawings, the disclosure, and the appended claims.

[0301] 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 construed as limiting their scope. Another aspect of the present invention may be as follows. [1] A sensor chip operably connectable to a detection device for detecting one or more biologically active substances in a surrounding medium, the sensor chip comprising: a reaction cell containing a plurality of receptor protein complexes; a membrane separating the reaction cell from the surrounding medium and permeable to the one or more biologically active substances; the receptor protein complex is configured to bind to the one or more biologically active substances in the reaction cell, thereby inducing a detectable state change in at least a portion of the receptor protein complex; and The sensor chip is at least partially removably insertable into the detection device for detecting the one or more biologically active substances. [2] The sensor chip described in [1], wherein the detectable one or more state changes of at least a portion of the receptor protein complex are indicative of the presence of the one or more biologically active substances in the surrounding medium. [3] The sensor chip of any one of [1] to [2], wherein the change in state of at least a portion of the receptor protein complex is associated with one or more of a change in conformational state of at least a portion of the receptor protein complex, a change in localization of at least a portion of the receptor protein complex within the reaction cell, a change in position of at least a portion of the receptor protein complex within the reaction cell, a change in composition of at least a portion of the receptor protein complex, a change in mass of at least a portion of the receptor protein complex, a change in mass of at least a portion of the reaction cell, a change in physical properties of at least a portion of the receptor protein complex, a change in physical properties of at least a portion of the reaction cell, a change in optical properties of at least a portion of the reaction cell, a change in chemical properties of at least a portion of the receptor protein complex, a change in chemical properties of a substrate contained within the reaction cell, a change in conductivity of a substrate contained within the reaction cell, or a change in concentration of free fluorescent molecules or light-absorbing molecules within at least a portion of the reaction cell. [4] The sensor chip described in any one of [1] to [3], wherein the receptor protein complex is configured to change its position within the reaction cell upon binding to the one or more biologically active substances. [5] A sensor chip described in any one of [1] to [4], wherein the surrounding medium includes at least one of ambient air and water. [6] The membrane is permeable to gases, and / or The sensor chip according to any one of [1] to [5], wherein the membrane is impermeable to water or aqueous liquids. [7] A sensor chip described in any one of [1] to [6], wherein the sensor chip is configured in a shape and size that allows it to be at least partially inserted into the detection device. [8] A sensor chip described in any one of [1] to [7], further comprising one or more connectors for operably connecting the sensor chip to the detection device. [9] The sensor chip described in any one of [1] to [8], further comprising one or more electrodes disposed at least partially within the reaction cell and configured to determine the conductivity of a substrate or composition within the reaction cell.

[10] A sensor chip described in any one of [1] to [9], further comprising at least one detection window that is semi-transparent to electromagnetic radiation emitted and / or scattered by at least one component of the receptor protein complex.

[11] A sensor chip described in any one of [1] to

[10] , further comprising at least one reservoir that can be fluidly connected to the reaction cell, the at least one reservoir being configured to supply deionized water to the reaction cell.

[12] The sensor chip described in any one of [1] to

[11] , wherein the receptor protein complexes each include at least one ligand-binding domain of the receptor protein, the ligand-binding domain being configured to bind to one or more biologically active substances and to change conformation upon binding to one of the biologically active substances.

[13] A detection device for detecting one or more biologically active substances in a surrounding medium, which can be operably coupled to at least one sensor chip according to any one of [1] to

[12] , wherein the detection device comprises: at least one sensor configured to determine a state change of at least some of the receptor protein complexes in the reaction cells of the at least one sensor chip, the state change being induced by binding of one or more receptor protein complexes with one or more biologically active substances that pass from the surrounding medium through a membrane of the sensor chip into the reaction cells of the sensor chip; and A detection device comprising a processing circuit coupled to the at least one sensor, the processing circuit configured to provide a detection signal indicative of the presence of the one or more biologically active substances in the surrounding medium based on determining a change in state of at least a portion of a receptor protein complex.

[14] The detection device described in

[13] , wherein the detection signal indicates the amount of one or more biologically active substances per volume of the surrounding medium, the mass of the biologically active substances per volume of the surrounding medium, the concentration of the biologically active substances in the surrounding medium, the ability of the surrounding medium to activate a receptor protein, and the biological activity of the surrounding medium.

[15] A detection system for detecting one or more biologically active substances in a surrounding medium, the detection system comprising: At least one sensor chip according to any one of [1] to

[12] above; A detection system comprising the detection device according to any one of

[13] and

[14] .

Claims

1. 1. A sensor chip operably coupleable to a detection device for detecting one or more biologically active substances in a surrounding medium, the surrounding medium comprising ambient air, the sensor chip comprising: a reaction cell containing a plurality of receptor protein complexes; a membrane separating the reaction cell from the surrounding medium and permeable to the one or more biologically active substances; at least a portion of the receptor protein complex is covalently bound to at least one functional surface of the reaction cell; the receptor protein complex is configured to bind to the one or more biologically active substances in the reaction cell, thereby inducing a detectable state change in at least a portion of the receptor protein complex; and The sensor chip is configured in a shape and size such that it is at least partially removably insertable into a socket of the detection device for detecting the one or more biologically active substances.

2. The sensor chip of claim 1 , wherein the detectable change in state of at least a portion of the receptor protein complex is indicative of the presence of the one or more biologically active substances in the surrounding medium.

3. 2. The sensor chip of claim 1, wherein the change in state of at least a portion of the receptor protein complex is associated with one or more of a change in conformational state of at least a portion of the receptor protein complex, a change in localization of at least a portion of the receptor protein complex within the reaction cell, a change in position of at least a portion of the receptor protein complex within the reaction cell, a change in composition of at least a portion of the receptor protein complex, a change in mass of at least a portion of the receptor protein complex, a change in mass of at least a portion of the reaction cell, a change in physical properties of at least a portion of the receptor protein complex, a change in physical properties of at least a portion of the reaction cell, a change in optical properties of at least a portion of the reaction cell, a change in chemical properties of at least a portion of the receptor protein complex, a change in chemical properties of a substrate contained within the reaction cell, a change in conductivity of a substrate contained within the reaction cell, or a change in concentration of free fluorescent molecules or light-absorbing molecules within at least a portion of the reaction cell.

4. The sensor chip of claim 1 , wherein the receptor protein complex is configured to change its position within the reaction cell upon binding to the one or more biologically active substances.

5. The sensor chip of claim 1 , wherein the surrounding medium comprises water.

6. the membrane is permeable to gases, and / or The sensor chip of claim 1 , wherein the membrane is impermeable to water or aqueous liquids.

7. The sensor chip of claim 1 , further comprising one or more connectors for operably coupling the sensor chip to the detection device.

8. The sensor chip of claim 1 , further comprising one or more electrodes disposed at least partially within the reaction cell.

9. The sensor chip of claim 1 , further comprising at least one detection window that is semi-transparent to electromagnetic radiation emitted and / or scattered by at least one component of the receptor protein complex.

10. The sensor chip of claim 1 , further comprising at least one reservoir fluidly connectable to the reaction cell, the at least one reservoir configured to supply deionized water to the reaction cell.

11. The sensor chip of claim 1, wherein the receptor protein complexes each comprise at least one ligand binding domain of a receptor protein configured to bind to one or more biologically active substances and to undergo a conformational change upon binding to one of the biologically active substances.

12. The sensor chip of claim 11, wherein the receptor protein is a hormone receptor protein.

13. 10. A detection device operably coupled to at least one sensor chip according to claim 1 for detecting one or more biologically active substances in a surrounding medium, said surrounding medium comprising ambient air, said detection device comprising: at least one socket that at least partially receives the at least one sensor chip; at least one sensor configured to determine a state change of at least a portion of a receptor protein complex in a reaction cell of the at least one sensor chip, wherein at least a portion of the receptor protein complex is covalently bound to at least one functional surface of the reaction cell, the state change being triggered by binding of the one or more receptor protein complexes with one or more biologically active substances that pass from the surrounding medium through a membrane of the sensor chip into the reaction cell of the sensor chip; and A detection device comprising a processing circuit coupled to the at least one sensor, wherein the processing circuit is configured to provide a detection signal indicative of the presence of the one or more biologically active substances in the surrounding medium based on determining a change in state of at least a portion of a receptor protein complex.

14. The detection device of claim 13, wherein the detection signal indicates the amount of one or more biologically active substances per volume of the surrounding medium, the mass of biologically active substances per volume of the surrounding medium, the concentration of biologically active substances in the surrounding medium, the ability of the surrounding medium to activate a receptor protein, and the biological activity of the surrounding medium.

15. 1. A detection system for detecting one or more biologically active substances in a surrounding medium, the detection system comprising: At least one sensor chip according to any one of claims 1 to 12; A detection system comprising: a detection device according to any one of claims 13 and 14.

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