Device and apparatus for sensing and analyzing the motional activity of a particle

Abstract

A device (1) for an analyzing apparatus (1000) configured to analyze a motional activity of a particle comprises at least one receptacle (2) configured to receive a sample comprising at least one particle, and at least one sensor element (3) being configured to sense a motional activity of the particle. The sensor element (3) is integrated into the receptacle (2). The receptacle (2) is at least partially insertable into at least one aperture (46) of a frame (45). The device (1) comprises at least one carrier element (24) that is configured to hold the receptacle (2). The carrier element (24) is configured to deform upon insertion of the receptacle (2) into the aperture (46) of the frame (45).

Description

[0001] TITLE

[0002] DEVICE AND APPARATUS FOR SENSING AND ANALYZING THE MOTIONAL ACTIVITY OF A PARTICLE

[0003] TECHNICAL FIELD

[0004] The present invention relates to a device for sensing a motional activity of a particle according to claim 1 , to an arrangement comprising such a device and a frame according to claim 8, to an analyzing apparatus comprising such an arrangement according to claim 12, to a method of producing such a device as claimed in claim 15, and to a method of analyzing the motional activity with such an apparatus according to claim 16.

[0005] PRIOR ART

[0006] The wide and often uncontrolled use of large spectrum antimicrobial drugs at a worldwide scale promotes the emergence of resistant strains. By using targeted antimicrobial therapy, patient mortality can be reduced, and recovery can be shortened. However, complete information typically needed for targeted antimicrobial therapy is usually delivered 2-3 days after a sample is taken. Current antimicrobial susceptibility tests (AST) may require more than 8 hours to determine and deliver relevant and useful information, which is typically not sufficient to provide a same day result.

[0007] Some automated systems shorten this time by interrogating microorganism growth in a plurality of test wells. For instance, WO 2017 / 185012 A1 discloses an automated rapid antimicrobial susceptibility testing system for performing a multi-assay testing sequence. The testing system is configured to receive a loaded test panel, move the loaded test panel to an incubation assembly, incubate and agitate an inoculated sample within the test panel in the incubation assembly, and periodically measure an amount of sample growth in a plurality of control wells of the test panel. Responsive to determining that a level of growth in the control wells meets or exceeds a threshold level of growth, incubation is stopped and end point assays on incubated samples in the test panel are performed, wherein an optical output from the sample in the wells of the test panel is measured. Some systems perform phenotypic testing of pathogenic organisms by exposing them to a set of antimicrobial dilution series and measuring their growth over time. Growth can be measured indirectly and most frequently optically by measuring solution turbidity or fluorescence of a dye triggered by microorganism metabolism. By quantitative comparison of optical signal, these systems determine the lowest concentration in dilution series of each antimicrobial that successfully inhibits growth of the tested microorganism. Such processes can be tedious and require proprietary analyzing algorithms that include analysis of absolute, relative values between wells, rates, integrals, etc., of growth curves.

[0008] Several years ago, an atomic force microscopy (AFM)-based nanomechanical sensor to assess the effects of drugs on the viability of particles such as bacteria in a timeframe of minutes has been disclosed in WO 2013 / 054311 A1. The detection is based on the observation that living particles oscillate at a nanometric scale and transfer these oscillations to a flexible support such as an AFM cantilever onto which they are attached. These oscillations last as long as the particle is alive but become weaker as soon as the viability of the particle is compromised by any chemical or physical means. Antibiotic or antifungal sensitivity tests are carried out by attaching the particle onto the AFM cantilever and monitoring its oscillations as a function of different antimicrobial drugs. However, the cantilever needs to be introduced into an analysis chamber in order to be exposed to the samples containing the particles to be analyzed. Such handling is complicated and prone to errors and contamination of the sample, for instance.

[0009] SUMMARY OF THE INVENTION

[0010] It is an object of the present invention to provide a device for sensing a motional activity of a particle that overcomes the drawbacks of the prior art. In particular, it is an object to provide a device which allows a fast sensing and a simplified handling at the same time while enhancing reliability.

[0011] This object is achieved with a device according to claim 1 . In particular, a device for sensing a motional activity of a particle is provided. The device comprises at least one receptacle configured to receive a sample comprising at least one particle, and at least one sensor element being configured to sense a motional activity of the particle. The sensor element is integrated into the receptacle. The receptacle is at least partially insertable into at least one aperture of a frame. The device comprises at least one carrier element that is configured to hold the receptacle. The carrier element is configured to deform upon insertion of the receptacle into the aperture of the frame.

[0012] The deformation of the carrier element is preferably caused by the frame, in particular by the arrangement and / or the design of the aperture of the frame. In particular, the frame and the carrier element are preferably configured to ensure an intended, i.e. correct, positioning of the receptacle and therefore of the sensor element. Again in other words, the frame and the carrier element preferably align the receptacle and therefore the sensor element. The deformability of the carrier element preferably enables compensation for slight misalignments arising from manufacturing tolerances, for instance. Unlike cartridges, test panels, etc. formed from rigid materials that cannot accommodate such deviations, the carrier element permits fine positional adjustment upon insertion of the receptacle, thereby achieving precise alignment without requiring prohibitively exact machining. This advantage significantly reduces manufacturing complexity and cost while enhancing assembly accuracy and reliability.

[0013] Since the sensor element is integrated into the receptacle that receives the sample to be analyzed, a handling of the device is simplified. In addition, external influences on the sensor element such as a contamination or damage of the sensor element can be minimized.

[0014] The sensor being integrated into the receptacle preferably means that the sensor element is directly or indirectly attached to the receptacle. The sensor element being indirectly attached to the receptacle preferably means that the sensor element is attached via a holding element, see further below.

[0015] The sensor element being configured to sense the motional activity of the particle allows an analysis of conditions of the particle being associated with the motional activity of the particle to be analyzed. In particular, the sensed motional activity is associated with a viability and / or a metabolic activity and / or a level of metabolic activity and / or a sensitivity and / or a resistance of the particle.

[0016] Moreover, the device enables a sensing of the motional activity of the particle before and / or during and / or after the particle is subjected to a chemical stimulus and / or a physical stimulus. For instance, if one were to analyze the effectiveness of a drug on particles such as antibiotics on bacteria or an anti-cancer drugs on cancer cells, the motional activity could be determined before the addition of the antibiotics to the bacteria or of the anti-cancer drugs to the cancer cells and after the addition of the antibiotics to the bacteria or of the anti-cancer drugs to the cancer cells, respectively. If the antibiotics or the anti-cancer drugs are effective, one would determine a difference in the motional activity. For instance, the killed bacteria or cancer cells would no longer exhibit a metabolic activity which is expressed in the sensed motional activity. The (in)effectiveness of the drug can be determined very quickly from the analysis of the motional activity of the particle without having to wait for growth, for example. Various analysis methods are conceivable in order to analyze the sensed motional activity, such as the analysis of a detected time-dependent signal as described in WO 2023 / 174728 A1. That is, it is conceivable to analyze changes of signal properties of the detected signal associated with the sensed motional activity in time, wherein the signal is detected for a plurality of points in time so as to obtain a timedependency of the signal, and wherein the time-dependency is analyzed in order to determine time-independent signal parameters. These signal parameters characterize the time variation of the signal. At least a selection of these signal parameters is then fed to a linking algorithm as the input variables, and wherein the linking algorithm provides at least one output variable being based on the input variables and being at least one activity indicator being indicative of the motional activity of the particle.

[0017] To this end it is particularly preferred that the device comprises a plurality of receptacles and wherein each receptacle comprises at least one sensor element. Any statements made with respect to a single receptacle likewise apply to two or more receptacles and vice versa.

[0018] The provision of a plurality of sensor elements allows a simultaneous or multi-analysis of one or more samples, respectively, whereby the analysis can be further accelerated.

[0019] The device allows an analysis of a variety of particles such as biological particles or non- biological particles. Examples of biological particles are at least one of a cell, a virus such as a phage, and a matter of biological origin such as peptides, proteins, polysaccharides, vesicles, protein-RNA co-polymers, protein-DNA co-polymers, capsules, spores, the matter of biological origin preferably being particulate. Examples of non-biological particles are at least one of a protein, a lipid, a nucleic acid such as DNA, a nanotube or nano-bead preferably made of elementary carbon metal oxides such as titanium oxide, a nanodevice, a glucide, a hydrocarbon, an aliphatic or aromatic polymer such as a phenolic polymer, and the like. The device allows an analysis of a variety of samples. For instance, the sample may be a fluid such as a biological fluid, e.g. blood, urine, cerebrospinal fluid, sputum, etc. However, other fluids such as non-biological fluids are likewise conceivable.

[0020] The carrier element preferably is compliant and / or configured to undergo a shape change and / or to elastically deform. Additionally, or alternatively, the carrier element preferably comprises or consists of at least one polymer, in particular of at least one thermoplastic polymer such as a thermoplastic elastomer (TPEs), low-density polyethylene (LDPE), ethylene-vinyl acetate (EVA), thermoplastic polyurethane (TPU), or polypropylene (PP), and / or at least one metal compound and / or an alloy such as a metal alloy, for instance steel.

[0021] That is, the carrier element preferably is compliant. In particular, the carrier element preferably comprises a material property and / or a geometrical property allowing deformation upon insertion of the receptacle into the aperture of the frame.

[0022] The deformation of the carrier element upon insertion of the receptacle into the aperture of the frame preferably is bending and / or flexing and / or stretching and / or twisting and / or compressing.

[0023] To this end it is conceivable that the carrier element is elastically deformable, such that it returns to its original shape upon removal of the receptacle from the frame. However, it is likewise conceivable that the carrier element performs permanently and / or plastically, for instance in the event of the carrier element having geometrical properties such as being thin, e.g. consisting of thin steel that can deform.

[0024] The carrier element preferably has a modulus of elasticity an / or a flexural modulus of 2000 MPA or less, for instance of 1500 MPA or less, such as 500 MPA or less, or 200 MPA or less, for example 100 MPA or less such as 50 MPA or less.

[0025] The carrier element preferably has an elongation at break of at least 50%, for instance at least 100% such as at least 300 %, for example at least 600% or at least 800%.

[0026] The carrier element preferably has a tensile strength of 1 MPa or more and / or of 100 MPa or less, for instance in the range of 2 MPa to 50 MPa.

[0027] The carrier element preferably has a tear resistance of 5 kN / m or more, such as at least 10 kN / m or at least 50 kN / m such as at least 8kN / m.

[0028] The deformation of the carrier element preferably encompasses dimensional changes in the range of tens of micrometers to hundreds of micrometers or more, for instance of at least 0.5 millimeter such as of at least 1 millimeter in one or more spatial directions relative to an original dimension of the carrier element. The original dimension of the carrier element is understood as the dimension of the carrier element in the absence of any external forces or stress acting on it, i.e. its unstressed or relaxed state.

[0029] In particular, a global or overall deformation of the carrier element along at least one spatial direction may be on the order of at least 0.5 millimeter to at least 1 millimeter. Said global or overall deformation refers to the overall displacement or dimensional change of the entire carrier element in a given spatial direction. As will be outlined in greater detail below, the carrier element can comprise a plurality of receptacles that can be arranged in a plurality of apertures of the frame. When considering the effect of said overall or global deformation on the relative positioning of these receptacles, the resulting displacement between adjacent or otherwise spaced-apart receptacles preferably is in the range of tens to hundreds of micrometers. That is, while the entire carrier element may deform by an amount on the order of millimeters, the relative positional change between receptacles preferably is typically within a range from tens to hundreds of micrometers.

[0030] The carrier element preferably comprises or consists of at least one polymer, preferably at least one thermoplastic polymer such as a thermoplastic elastomer (TPEs), low-density polyethylene (LDPE), ethylene-vinyl acetate (EVA), thermoplastic polyurethane (TPU), or polypropylene (PP). The thermoplastic elastomer is preferably selected from styrene- ethylene-butylene-styrene (SEBS) block copolymers or urethane-based elastomers.

[0031] Additionally or alternatively, the carrier element comprises or consists of at least one metal compound and / or at least one alloy such as a metal alloy, for instance steel. Other materials are however likewise conceivable.

[0032] The receptacle preferably is rigid and / or stiff and / or non-deformable. Additionally or alternatively, the receptacle and the carrier element can be a single-piece element or can be separate components.

[0033] The receptacle can comprise or consist of the same material or of a different material as the carrier element.

[0034] For instance, the receptacle can comprise or consist of at least one polymer, plastic, metal, ceramic, glass, silicon, or combinations thereof. Preferred polymers are amorphous polymers or copolymers such as cyclic olefin copolymer (COC) or cyclo-olefin-polymer (COP). Preferred plastics are transparent plastics and / or thermoplastics such as polycarbonate (PC), poly(methyl methacrylate) (PMMA) or polystyrene (PS). However, other materials are likewise conceivable.

[0035] The receptacle preferably comprises or consists of a stiffer and / or more rigid material than the carrier element.

[0036] In particular, it is preferred that the receptacle and the carrier element are made of two different materials, in particular of two different polymer compounds, wherein the receptacle preferably is rigid and / or stiff and / or non-deformable, and wherein the carrier element preferably is compliant and / or deformable.

[0037] The receptacle and the carrier element being a single-piece element preferably means that they are a monolithic component. That is, the receptacle and the carrier element can be made as a single, integral piece for instance via co-molding or single-part molding. However, it is likewise conceivable that the receptacle and the carrier element are separate components preferably being assembled. That is, in the latter case it is conceivable that the receptacle and the carrier element are manufactured separately from one another in a first step and are then assembled or joined together in a second step. In this case, it is preferred that the carrier element comprises at least one receiving opening for receiving the at least one receptacle. As will be explained in greater detail below, the device preferably comprises a plurality of receptacles. In this case it is preferred that the carrier element comprises a plurality of receiving openings as well, and wherein one receptacle is received in a corresponding receiving opening. The receptacle can be arranged in the receiving opening of the carrier element via a form-fit and / or a press-fit and / or force-fit. Additionally or alternatively, at least one adhesive element, such as a glue, resin, or bonding agent, may be provided to connect the receptacle to carrier element. The device preferably is disposable.

[0038] In any case, the carrier element preferably has a flat shape and / or extends primarily along a first and second orthogonal dimensions and to a lesser extend along a third dimension perpendicular to said first and second dimensions. Said first and second dimensions can be referred to as a length and a width of the carrier element, which are preferably larger than the third dimension being a depth or thickness of the carrier element. For instance, the carrier element can be in the form of a strip or plate such as a rectangular or squared plate.

[0039] The at least one receptacle preferably extends along the third dimension or the depth or thickness of the carrier element, respectively, and protrudes from a bottom side of the carrier element. That is, a length of the receptacle along this third dimension is preferably greater than the length or the thickness of the carrier element, such that the receptacle projects outwardly relative to the flat carrier element. This configuration allows the receptacle to be inserted into the aperture of the frame when arranging the carrier element on the frame, see further below.

[0040] In any case, the receptacle preferably comprises a top side and an opposite bottom side. The bottom side of the receptacle preferably protrudes from the bottom side of the carrier element and / or the top side of the receptacle is preferably flush with the top side of the carrier element or protrudes from the top side of the carrier element.

[0041] The receptacle preferably extends entirely through the carrier element with respect to the third direction or the depth or thickness of the carrier element, respectively. Hence, in the event that the carrier element comprises a receiving opening in which the receptacle is received, it is preferred that said receiving opening is a through-opening.

[0042] The sensor element preferably comprises at least one flexible support being configured to oscillate due to a motional activity of the particle. The flexible support preferably is a cantilever, a membrane such as a graphene drum, or a bridge. Other sensor elements are however likewise conceivable. For instance, the sensor element can be any type of MEMS sensor that can potentially measure particle oscillations such as cell oscillations or the like.

[0043] That is, the sensor element, in particular the flexible support, is preferably configured to sense the motional activity of the particle via oscillations being induced into the sensor element, in particular into the flexible support, by the particle. The sensor element can be made of a variety of materials. For instance, the sensor element may comprise or consist of at least one polymer and / or at least one plastic, for instance a thermoplastic polymer or plastic, respectively. For example, the sensor element can comprise or consist of silicone and / or polyether ether ketone (PEEK), although a variety of other polymers and / or plastic are likewise conceivable. Additionally, or alternatively, the sensor element may comprise or consist of a silicate and / or silica such as silicon dioxide, for instance quartz. Additionally, or alternatively, the sensor element may comprise or consist of at least one allotrope of carbon such as graphene. Additionally, or alternatively, the sensor element may comprise or consist of silicone nitride. Additionally, or alternatively, the sensor element may comprise or consist of at least one amorphous solid such as glass. Additionally, or alternatively, the sensor element may comprise or consist of at least one metal compound.

[0044] The sensor element can comprise two or more flexible supports. Said two or more flexible supports are preferably arranged in an array. Additionally, or alternatively, said two or more flexible supports are preferably arranged on one lateral side or on two or more lateral sides of the sensor element. The provision of several flexible supports on a sensor element allows redundant measurements and / or multiple measurements performed by the same sensor element.

[0045] The sensor element preferably comprises a sensor body, and wherein the flexible support(s) are attached to or are integrally formed on the sensor body. The sensor body preferably is a so-called chip or a die.

[0046] The sensor element, in particular the sensor body, preferably is in the micrometer to millimeter range and / or has a surface area of 1000 micrometer x 1000 micrometer or less, for instance 500 micrometer to 500 micrometer. An inner diameter of the receptacle preferably is in the millimeter range and / or 10 millimeter or smaller, for instance 5 millimeter or smaller such as about 2 millimeter. Additionally, or alternatively, a preferred inner diameter of the receptacle preferably is in the range of 2 millimeter to 10 millimeter. A volume of the receptacle preferably is in the microliter range and / or between 1 microliter to 500 microliter, such as between 10 microliter to 250 microliter.

[0047] The flexible support preferably comprises at least one reflective element configured to reflect incident electromagnetic radiation. Said reflective element preferably is a reflective coating. Additionally, or alternatively, the reflective element preferably extends partially or entirely along the flexible support.

[0048] The reflective element is preferably provided on a top side of the flexible support facing away from a side of the receptacle. Additionally, or alternatively, the reflective element is preferably provided on a bottom side of the flexible support facing a side of the receptacle. Additionally, or alternatively, the reflective element is preferably arranged on the flexible support such as to face a detector device being configured to detect the motional activity sensed by the sensor element, see further below. In fact, the reflective element can be arranged on any side of the flexible support and preferably serves the purpose of enhancing an optical readout of the sensed motional activity by an optical detection device.

[0049] If reference is made herein to a particular side of the receptacle, this is usually related to an arrangement of the sensor element in the receptacle. In principle, the sensor element can be integrated on any side of the receptacle, which is why statements relating to a particular side of the receptacle also apply to other sides. For the sake of simplicity, reference is sometimes made herein to the bottom side of the receptacle. This is particularly the case if the sensor element is integrated at the bottom side. But as just noted, the sensor element can also be integrated on another side, e.g. on one of the lateral sides of the receptacle.

[0050] The sensor element, in particular the flexible support, can be at least regionally functionalized with at least one functionalization to enhance an attachment of the particle. Various functionalizations are conceivable and are well-known in the art. For instance, the functionalization can be a chemical functionalization or a physical functionalization that enhance the attachment of the particles. That is, it is preferred that the particles are attached to a surface of the flexible support before being analyzed. Said attachment is preferably done according to methods as known in the state of the art such as by functionalizing the surface of the flexible support or by using attachment compounds known in the art, respectively. It is particularly preferred that the particles are attached to the surface of the flexible support as described in WO 2021 / 130339 A1 , which is incorporated herein by reference. That is, it is preferred that the particles are dispersed in a solution comprising at least one of a gelling agent, a gellable agent and a thickening agent, and wherein said dispersion is subsequently added to the surface of the flexible support. Additionally, or alternatively, the functionalization can be a physical functionalization as described in WO 2021 / 130339 A1 as well, wherein a surface structure is provided on the surface of the flexible support. The functionalization can be unspecific or specific with regard to the particles to be attached, i.e. it can be configured for a general attachment or for a selective attachment of target particles only. The latter is of advantage when certain particles in a mixture should only attach, and the rest be discarded such as washed away for instance.

[0051] The functionalization preferably extends partially or entirely along the sensor element, in particular along the flexible support. The functionalization is preferably provided on a top side of the sensor element, in particular on the top side of the flexible support, facing away from a side such as the bottom side of the receptacle. Additionally, or alternatively, the functionalization is preferably provided on a bottom side of the sensor element, in particular on the bottom side of the flexible support, facing a side such as the bottom side of the receptacle.

[0052] However, it is likewise conceivable that the particles are not attached to the sensor element but that the device, in particular the sensor element, is configured to sense the motional activity of free-floating particles.

[0053] The sensor element can be directly attached to an inner side of the receptacle. Alternatively, the sensor element can be indirectly attached to an inner side of the receptacle via at least one holding element being attached to the sensor element and to the inner side of the receptacle.

[0054] The sensor element is preferably directly attached to the inner side of the receptacle via at least one of: bonding such as gluing, chemical bonding or anodic bonding, molding, press joining, or mechanical interfaces being provided on the sensor element and the inner side receptacle.

[0055] The holding element is preferably attached to the inner side of the receptacle and / or to the sensor element via at least one of: bonding such as gluing, chemical bonding or anodic bonding, molding, welding such as plastic welding, press joining, or mechanical interfaces being provided on the sensor element and the inner side of the receptacle.

[0056] The holding element preferably comprises or consists of at least one of: plastic, metal, ceramic, glass, silicon, or combinations thereof. Preferred polymers are amorphous polymers or copolymers such as cyclic olefin copolymer (COC) or cyclo-olefin-polymer (COP). Preferred plastics are transparent plastics and / or thermoplastics such as polycarbonate (PC), poly(methyl methacrylate) (PMMA) or polystyrene (PS). However, other materials are likewise conceivable. The holding element preferably comprises or consist of the same material as the receptacle is made of.

[0057] The sensor element preferably comprises at least one sensor-alignment-element that aligns the sensor element with respect to the receptacle and / or with respect to a holding element. The sensor-alignment-element preferably is a recess or opening being formed in the sensor element. The sensor-alignment-element is preferably aligned with respect to a counterpart receptacle-alignment-element provided in the receptacle and / or a counterpart holding- alignment-element provided on the holding element.

[0058] That is, the sensor element may have alignment elements that support the integration, in particular the alignment and possibly also a fixation, of the sensor element in the receptacle or on the holding element, respectively. Such an alignment enables a highly reproducible alignment of the sensor element.

[0059] Hence, the holding element may comprise at least one holding-alignment-element that aligns the holding element with respect to the receptacle. The holding-alignment-element preferably is a recess or opening being formed in the holding element.

[0060] That is, the sensor-alignment-element and the holding-alignment-element in the form of recesses or openings preferably serve the purpose of a visual aid or orientation aid and thereby enable an alignment.

[0061] Furthermore, the holding element can be arranged and configured such as to protect the sensor element from mechanical influences. To this end it is preferred that the holding element at least partially surrounds and thereby protects the sensor element.

[0062] The receptacle-alignment-element preferably is a protrusion or post formed in the receptacle. To this end it is preferred that the sensor-alignment-element in the form of the recess or opening is engaged with the receptacle-alignment-element in the form of the protrusion or post.

[0063] As will be explained in further below, the receptacle-alignment-element can additionally also be configured as a stabilizing element that stabilizes the sensor element within the receptacle.

[0064] The sensor element, in particular the flexible support, is preferably located at a distance from a bottom side of the receptacle, for instance from a bottom side of the receptacle. However, the sensor element can be located at a distance from any other side of the receptacle as well.

[0065] Additionally, or alternatively, a gap is preferably formed between a side of the receptacle such as the bottom side of the receptacle and the sensor element, in particular the flexible support. Said gap is particularly preferably provided by the holding element. That is, if a holding element is present, it is preferred that the holding element attaches the sensor element to an inner side of the receptacle such that a gap is formed between the sensor element and a side such as the bottom side of the receptacle. The gap preferably is in the range of 0.1 millimeter to 1 millimeter.

[0066] The holding element can extend over an entire side of the receptacle such as over the entire bottom side of the receptacle.

[0067] Alternatively, it is likewise conceivable that the holding element extends only partially along a side of the receptacle, e.g. only partially along the bottom side, and leaves at least one uncovered part on the side of the receptacle. The sensor element is preferably arranged on the holding element in such a way that the sensor element, in particular the flexible support, extends at least partially over the uncovered part of the holding element. Additionally, or alternatively, the holding element can comprise at least one recess, and wherein the sensor element, in particular the flexible support, is at least partially arranged in a region of said recess. Said uncovered part and / or said recess preferably define a sub-volume or a first volume level of a total volume defined by the receptacle. In fact, this design allows to decrease the receptacle’s volume while handling expensive substances and media, e.g. smaller volumes for particle attachment, e.g. for a loc inoculum concentration, and allows a bigger volume for other steps. In other words, the receptacle is designed in a way to allow for different volumes, wherein the holding element with the recess defines here two volumes. The smaller volume level, i.e. the sub-volume or the first volume level defines the amount of particle suspension needed for attachment of the particles to the sensor element.

[0068] At least part of the receptacle, preferably at least a side of the receptacle such as the bottom side of the receptacle, is transparent or translucent and / or configured to transmit electromagnetic radiation.

[0069] A side of the receptacle can be straight or can be at least regionally inclined and form at least one inclination. Additionally, or alternatively, the sensor element, in particular the flexible support, can be arranged parallel to a side of the receptacle or sensor element, in particular the flexible support, can be arranged inclined in the receptacle.

[0070] For instance, a side such as the bottom side of the receptacle can be straight, i.e. without any inclinations but extending within a plane. To this end it is preferred that the sensor element, in particular the flexible support, is arranged in the receptacle such that it extends parallel to the side such as the bottom side of the receptacle.

[0071] However, it is likewise conceivable that the side such as the bottom side of the receptacle is not straight but comprises at least one inclination. To this end it is preferred that the sensor element, in particular the flexible support, is arranged in a region of said inclination and such that the sensor element, in particular the flexible support, is arranged inclined inside the receptacle.

[0072] The device can comprise at least one stabilizing element that is configured to stabilize the sensor element, in particular the flexible support. Additionally, or alternatively, the device can comprise at least one sealing element that seals the receptacle towards an outside, the sealing element preferably being removable from the receptacle.

[0073] That is, the sensor element, in particular the sensor body, is preferably stabilized via at least one stabilizing element in order to prevent damages of the sensor element due to external influences, in particular mechanical influences especially during transportation of the device. In particular, the stabilizing device preferably stabilizes the sensor element so that it does not become loose due to external shocks, e.g. during transportation.

[0074] To this end the stabilizing element can temporarily or permanently secure or connect the sensor element to the receptacle, whereby the sensor element is secured against displacement.

[0075] In a first variant, the stabilizing element can be arranged removably in the receptacle and can be removed before using the device for sensing the particle. For instance, the stabilizing element can be a removable pin or plate that presses against the sensor element.

[0076] In a second variant, the stabilizing element can be arranged non-removable in the receptacle, i.e. permanently. To this end it is preferred that the stabilizing element is arranged inside the receptacle and in contact with the sensor element, in particular with the sensor body. For example, the stabilizing element can have the shape of a pin or plate that is glued or otherwise attached to the receptacle and the sensor element. To this end it is particularly preferred that said stabilizing element also serves the purpose of aligning with the sensor element and can at the same time also provide the receptacle-alignment- element mentioned earlier, i.e. the counterpart alignment element to the sensor-alignment- element.

[0077] The sealing element is preferably arranged on the top side of the receptacle seals an inside of the receptacle towards an outside, whereby the inside of the receptacle is protected against external influences such as contamination and / or sterile conditions during handling prior to the analysis can be maintained. Hence, the receptacle is preferably sterile.

[0078] The sealing element is preferably removable from the receptacle. The stabilizing element can be in connection with the sealing element. For instance, the stabilizing element can be a pin that protrudes from a bottom side of the sealing element facing an inside of the receptacle and that extends into the receptacle to the sensor element being arranged at the bottom side of the receptacle, and wherein its free end presses against the sensor element.

[0079] When seen in cross-section, a shape of the receptacle at least in a region of the bottom side of the receptacle is preferably circular, polygonal, rectangular, multi angled, elliptical, squared, or non-centrosymmetric. Additionally, or alternatively, lateral sides of the receptacle are preferably tapering inwards when seen from a top side of the receptacle towards a bottom side of the receptacle. These shapes preferably provide a manufacturing aid and / or are self-centering that allow an easier insert of the receptacle into the aperture of the frame.

[0080] The receptacle can comprise at least one port configured to inlet at least one fluid into the receptacle and / or to outlet at least one fluid out of the receptacle. The port is preferably provided in a region of a bottom side of the receptacle.

[0081] The fluid can comprise or consist of the sample to be analyzed, i.e. a sample fluid. Said sample fluid can be introduced into the receptacle via the at least one port for analysis of the sample fluid, i.e. for analyzing a motional activity of a particle in the sample. Additionally, or alternatively, the sample fluid can be removed from the receptacle via the at least one port after the analysis of the sample fluid. The fluid can be a washing fluid that serves the purpose of cleaning or washing the receptacle. Said washing fluid can be introduced into the receptacle and / or can be removed from the receptacle via the at least one port. Hence, the port can be seen as a fluid drain.

[0082] Especially in the event, that the port serves to remove fluid from the receptacle it is preferred that said port is provided in a region of the bottom side of the receptacle.

[0083] The device can further comprise at least one cover element that covers the receptacle. The cover element preferably seals the receptacle in a liquid tight and / or gas tight manner towards an outside. Additionally, or alternatively, the cover element preferably comprises at least one inlet for introducing fluids into the receptacle and / or at least one outlet for removing fluids out of the receptacle. Additionally, or alternatively, the cover element preferably comprises at least one fluid channel. This cover element can be provided in addition to the sealing element comprising the stabilizing element mentioned earlier. However, it is likewise conceivable that this cover element comprises the at least one stabilizing element mentioned earlier.

[0084] The cover element preferably covers and thereby seals the receptacle in a liquid tight and / or gas tight manner. Sterile conditions within the receptacle can thereby be maintained.

[0085] Additionally, or alternatively, the cover element can comprise at least one inlet that allows an introduction of fluids such as various gasses into and / or at least one outlet that allows a removal of the fluids out of the receptacle to create and / or control specific atmospheric conditions, e.g. microaerophilic, anaerobic etc. Furthermore, the inlet and / or outlet enables an atmosphere control for specific applications, e.g. they allow an adjustment or selection of concentrations of gasses over a culture media in the receptacle, etc.

[0086] Said outlet can be provided in addition to the port provided in the receptacle as mentioned earlier or instead of such a port.

[0087] The inlet and outlet can be provided as separate elements. However, it is likewise conceivable that the inlet and outlet are provided by a common element that serves the purpose of introducing as receptacle as removing fluids.

[0088] The device can comprise a plurality of receptacles, and wherein each receptacle comprises at least one sensor element. The sensor elements in the plurality of receptacles can be the same in all receptacles or two or more of the receptacles can comprise different sensor elements.

[0089] Any statements made with respect to a single receptacle likewise apply to two or more receptacles and vice versa.

[0090] For instance, if the receptacles are sealed with a sealing element, it is conceivable that each receptacle comprises an individual sealing element. However, it is likewise conceivable that two or more of the receptacles share a common sealing element.

[0091] Likewise, it is conceivable that the receptacles are covered with individual cover elements or that two or more receptacles share a common cover element. In the latter case it is preferred that the cover element comprises two or more inlets and / or outlets, such that each receptacle comprises its inlet and / or outlet. Said two or more inlets and / or outlets are preferably in fluid connection with one another via at least one fluid channel.

[0092] In another aspect, an arrangement is provided, wherein the arrangement comprises at least one device as described above and at least one frame comprising at least one aperture, wherein the receptacle is preferably removably insertable into the aperture of the frame. The device preferably comprises a plurality of receptacles that are held by the at least one carrier element and that are insertable into a plurality of apertures of the frame.

[0093] Any statements made with respect to the device as such preferably likewise apply to the arrangement comprising the device and vice versa.

[0094] The carrier element and the frame are preferably separate components, i.e., individual parts. As such, the carrier element can be arranged on the frame and can be removed from the frame as needed. Consequently, the receptacle is preferably insertable into the aperture of the frame and removable therefrom.

[0095] Preferably, the carrier element and the at least one receptacle are disposable. The frame can be disposable or re-usable.

[0096] The carrier element preferably comprises a plurality of receptacles and the frame preferably comprises a plurality of apertures, and wherein each receptacle of the plurality of receptacles is preferably at least partially insertable into a corresponding aperture of the plurality of apertures.

[0097] Upon insertion of the receptacles into the apertures of the frame, the carrier element is preferably deformed.

[0098] The frame preferably comprises or consists of at least one metal compound and / or at least one ceramic material. Conceivable metal compounds are pure metals, metal alloys, or intermetallic compositions, and include but are not limited to rigid, thermally conductive metals such as copper, aluminium, and steels including austenitic and martensitic stainless steels, corrosion-resistant steels, etc. Conceivable ceramic materials are glass-ceramics such as MACOR®, Corning Inc., oxide ceramics, nitride ceramics, carbide ceramics, etc. However, it should be noted that many other materials are likewise conceivable and are well-known in the art.

[0099] The frame preferably is rigid and / or thermally conductive and / or is heat-retaining.

[0100] The frame being rigid preferably means that the frame is configured to resist an elastic deformation under applied mechanical loads. Additionally or alternatively, the frame preferably comprises or consists of at least one material, in particular at least one metal compound and / or at least one ceramic material, that has a stiffness and / or Young's modulus of at least 50 GPa such as at least 100 GPa and / or a yield strength of at least 50 MPa such as at least 200 MPa.

[0101] In any case, it is preferred that the frame is configured to provide mechanical rigidity and / or enable a temperature control via thermal conduction. In other words, the frame preferably has a heat conductivity and heat capacity that prevent the device from unwanted thermal drifts that may cause XYZ dimension crawling leading to setup mechanical instability.

[0102] The frame comprises a top side and an opposite bottom side. The at least one aperture of the frame preferably extends from the top side of the frame at least partially towards the bottom side of the frame. Upon insertion of the receptacle into the aperture of the frame, a bottom side of the carrier element is preferably arranged on the top side of the frame. In other words, to insert the receptacle into the aperture of the frame, the carrier element is preferably arranged on the top side of the frame. The receptacle and the aperture are preferably configured to enter a form-fit and / or a press- fit and / or force-fit upon insertion of the receptacle into the aperture of the frame. Additionally or alternatively, the aperture of the frame preferably comprises at least one aperture- receptacle-alignment element and / or the receptacle preferably comprises at least one receptacle-aperture-alignment element that align the receptacle with respect to the frame upon insertion of the receptacle into the aperture of the frame.

[0103] The aperture-receptacle-alignment element and / or the receptacle-aperture-alignment elements are preferably complementary to one another and / or are preferably provided by means of an asymmetric shape. For instance, the aperture-receptacle-alignment element of the aperture and / or the receptacle-aperture-alignment of the receptacle can be a flat wall or an inclined wall of otherwise inclined walls or flat walls, respectively. As an example, the aperture can comprise an aperture-receptacle-alignment element in the form of a conically tapered wall, and the receptacle can correspondingly comprise a receptacle-aperture- alignment element in the form of a matching conically tapered wall, such that the receptacle is guided into a predefined position during insertion, thereby enhancing the alignment effect and ensuring a unique mating orientation between the receptacle and the aperture.

[0104] The frame, in particular in a region of the aperture, preferably comprises at least one positioning element configured to connect to and / or align at least one interrogation unit configured to interrogate the sensor element with respect to the frame, in particular with respect to the aperture. Additionally or alternatively, the frame, in particular in the region of the aperture, preferably comprises at least one receiving cavity configured to at least partially receive an interrogation unit configured to interrogate the sensor element.

[0105] The interrogation unit preferably comprises or consists of at least one detection device and / or at least one radiation device as explained in further detail below.

[0106] The positioning element may include, but is not limited to, a slot, opening, recess, groove, pin, protrusion, rail, guide channel, etc. In any case, the positioning element is preferably arranged to define a precise location for the positioning of the interrogation unit on the frame.

[0107] To this end it is particularly preferred that the positioning element is arranged in a region of the aperture and thus in a region of the receptacle and consequently of the sensor element when the receptacle is received in the frame. In a region of the aperture preferably means that the interrogation unit can be connected and / or aligned with respect to the aperture and thus the sensor element in close spatial proximity and optimal alignment between the sensor element and the interrogation unit. Thereby, an interrogation of the sensor element by the interrogation unit, in particular an irradiation of the sensor element via the irradiation device and / or a detection of a sensed motional activity of the particle by the sensor element by the detection device, can be performed with minimal signal loss and reduced optical or thermal path lengths, whereby an accuracy, sensitivity, and reliability of the interrogation is enhanced.

[0108] For example, the interrogation unit being arranged in a region of the aperture can be connected to and / or at least partially received in a positioning element in the form of a recess, aperture or the like being formed in the frame and in a vicinity of the aperture.

[0109] For example, a positioning element in the form of an opening or slot or the like may be formed in the frame such that, with respect to the thickness or depth of the frame, it is located beneath the aperture of the frame. In other words, the frame may comprise an aperture that extends partially into the frame from the top side of the frame, along the thickness or depth of the frame, and the opening, slot or the like extends partially into the frame from the opposite bottom side of the frame, likewise along the thickness or depth of the frame. Both the aperture and the opening or slot or the like thus extend into the frame from opposite directions. A portion of the frame preferably remains between the aperture and the opening or slot or the like, thereby separating the two and maintaining structural integrity. In other words, the aperture does not open into the positioning element, although it is in principle conceivable.

[0110] Additionally or alternatively, the frame may comprise at least one receiving cavity in particular in the region of the aperture, the receiving cavity being configured to at least partially receive the interrogation unit.

[0111] The receiving cavity may include, but is not limited to, a slot, opening, recess, groove, guide channel, etc.

[0112] The receiving cavity can be provided in addition or in the alternative of the positioning element. However, it is likewise conceivable that the receiving cavity and the positioning element are provided by a same, common element. As mentioned earlier, the carrier element preferably comprises a plurality of receptacles and the frame preferably comprises a plurality of apertures. In this case it is preferred that the frame furthermore comprises a plurality of positioning elements, wherein at least one positioning element is associated with a particular aperture in order to connect and / or align at least one interrogation unit of a plurality of interrogation units, and / or that the frame furthermore comprises a plurality of receiving cavities, wherein at least one receiving cavity is associated with a particular aperture in order to at least partially receive at least one interrogation unit associated with said aperture and thus the receptacle and sensor element insertable therein.

[0113] In other words, it is preferred that at least one interrogation unit is associated and in particular connected to and / or aligned with respect to an aperture of the frame and thus with a receptacle and in particular with a sensor element received in the aperture of the frame.

[0114] The arrangement is configured such that each of the plurality of sensor elements of a plurality of receptacles can be interrogated individually and / or in parallel, i.e. at the same time. Furthermore, the arrangement preferably enables an interrogation of just a selection, i.e. of a subset of the receptacles and thus of the sensor elements. In other words, it is not mandatory that all receptacles are interrogated at a time.

[0115] Additionally or alternatively, the arrangement preferably allows the provision of a configurable amount of receptacles in the apertures of the frame and thus a configurable interrogation of the sensor elements.

[0116] For instance, a carrier element comprising six receptacles can be provided, wherein said receptacles are provided in six apertures of the frame. To this end it is conceivable that the frame comprises six apertures or more. That is, a number of apertures preferably corresponds or exceeds a number of receptacles.

[0117] For instance, the frame can comprise twelve apertures, wherein one carrier element comprising six receptacles, one carrier element comprising twelve receptacles, two carrier elements comprising in each case six receptacles, etc. can be arranged on the frame. Or, more generally speaking, the frame can comprise apertures and optionally also positioning elements in a custom designed number and provided, for instance, as an array along lines and columns allowing parallel and / or individual interrogations by the interrogation unit(s). Regardless of the number of carrier elements and / or receptacles, the frame with its apertures is positioning each receptacle in a predefined location ensuring alignment with the interrogation unit(s). An additional positioning or adjustment of the interrogation unit(s) such as the detection device(s) and / or the radiation source(s) can be dispensed with.

[0118] In another aspect, an analyzing apparatus configured to analyze a motional activity of a particle is provided. The analyzing apparatus comprises at least one arrangement as described above, and at least one analyzing unit configured to analyze the sensed motional activity of the particle. The analyzing apparatus can optionally further comprise at least one interrogation unit configured to interrogate the sensor element. The interrogation unit preferably comprises at least one detection device and / or at least one radiation device. The detection device is preferably configured to detect a motional activity sensed by the sensor element. In this case it is preferred that the detection device generates at least one detection signal upon the detection of the sensed motional activity and transmits said detection signal to the analyzing unit, and wherein the analyzing unit anayzes the detection signal. The detection device is preferably configured to detect an oscillation of the flexible support due to a motional activity of the particle.

[0119] Any statements made herein regarding the arrangement as such preferably likewise apply to the apparatus comprising the arrangement and vice versa.

[0120] The analyzing unit is preferably configured to analyze the sensed motional activity, and in particular one or more detection signals generated by the detection device upon detection of the sensed motional activity of the particle. As mentioned initially, various analysis methods are conceivable such as the analysis of a detected time-dependent signal that comprises the analysis of a time-dependency of the signal to derive a plurality of signal parameters that characterize a variation of the signal as a function of time, and wherein at least one activity indicator is determined that is indicative of the motional activity of the particle as described in WO 2023 / 174728 A1 which is incorporated herein by reference.

[0121] The detection device is preferably configured for an electromagnetic detection, in particular an optical detection, and / or electrical and / or magnetic and / or mechanical detection.

[0122] The detection device being configured for optical detection preferably is an optical detection device as it is known in the field of the art. For instance, the detection device can be a photodetector, a camera or an interferometer. The photodetector can be configured and arranged such as to detect electromagnetic radiation being emitted from a source of electromagnetic radiation onto the sensor element and then being reflected from the sensor element, see further below. In particular, it is preferred that the photodetector is configured and arranged such as to detect a change of the reflected electromagnetic radiation position, i.e. the photodetector preferably is a position sensitive detector. The camera can be configured and arranged such as to visually inspect and / or detect a position of the sensor element, in particular an XYZ position of the sensor element. To this end it is conceivable that the sensor element comprises at least one marking element that is recognized by the camera. In other words, the camera is preferably configured for image recognition.

[0123] In the event of the detection device being an interferometer, it is preferred that an interferometric cavity is formed within the receptacle, in particular between the sensor device and a side of the receptacle, for instance the bottom side of the receptacle. For example, the sensor element in the form of a cantilever can be directly or indirectly attached to the bottom side of the receptacle and can optionally further comprise at least one reflective element configured to reflect incident electromagnetic radiation on a bottom side of the cantilever facing the bottom side of the receptacle. The bottom side of the receptacle preferably is transparent or translucent. To this end, an interferometric cavity is formed between the oscillating part of the cantilever and the bottom side of the receptacle allowing placing of the interferometer head a few centimeters away from the interferometric cavity. In particular, it is preferred that the interferometer comprises a photodetector being configured and arranged such as to detect a change of the reflected electromagnetic radiation intensity.

[0124] The detection device being configured to electrical detection preferably is an electrical detection device as it is known in the field of the art. For instance, the detection device can be a piezoelectric detection device, a piezoresistive detection device, or capacitive detection device. To this end it is preferred that the detection device is in electrical connection with one or more electrodes being provided in the device, in particular in the receptacle. That is, the device, in particular the receptacle, preferably comprises one or more electrodes, wherein said electrodes are preferably integrated.

[0125] The apparatus can further comprise at least one radiation device configured to irradiate electromagnetic radiation onto the sensor element in the event that the detection device is configured for an optical readout. Said radiation device can be provided in addition to the detection device or the detection device and the radiation device can be provided by a single component such as a camera. The radiation device can be configured to emit electromagnetic radiation in the UV and / or VIS and / or IR region of the electromagnetic spectrum. Additionally, or alternatively, the radiation device can be configured to emit electromagnetic radiation of a fixed or sweeping wavelength. Sweeping wavelengths can enhance the resolution of the detection.

[0126] That is, the motional activity sensed by the sensor element can be detected in a variety of ways. A concrete example is now given for illustrative purposes. For instance, the sensor element can comprise a flexible support such as an oscillating cantilever. The oscillations of the flexible support can be detected by optical detection, wherein changes of position of a spot caused by laser light being irradiated from a radiation device and being reflected from the surface of the flexible support are measured with an optical detector such as a photodetector, particularly preferably with a position sensitive photodetector. The changes of position of the spot cause changes of signal recorded by the detector.

[0127] The interrogation unit, in particular the detection device and / or the radiation device, is preferably located outside of the receptacle.

[0128] Additionally, or alternatively, the interrogation unit, in particular the detection device and / or the radiation device, is preferably facing a bottom side of the receptacle and / or a lateral side of the receptacle. Additionally, or alternatively, the detection device and the radiation device can be located with respect to a same side or a different side of the receptacle.

[0129] The arrangement, in particular the device and / or the frame, and / or the interrogation unit, in particular the detection device and / or the radiation device, can be immovable..

[0130] The radiation device can comprise at least one lightguide, preferably an optical fiber, that is configured to guide the electromagnetic radiation to the receptacle. In the event that the device comprises a plurality of receptacles the radiation device preferably comprises a plurality of lightguides that guide the electromagnetic radiation to each of the receptacles.

[0131] For example, if the device comprises a plurality of receptacles each comprising at least one sensor element, the lightguides can guide radiation to the plurality of receptacles and light reflected from the sensor elements can be guided to the detection device. However, it is likewise conceivable that no lightguide(s) and in particular no optical fiber(s) is present and / or that the interrogation unit(s), in particular the detection device(s) and the radiation device(s), are preferably miniaturized bulk optics such as free-air optics or free- space optics, respectively, see further below.

[0132] In any case, it is conceivable that a plurality of interrogation units, in particular detection devices and radiation devices, are provided that are assigned to the plurality of receptacles, and wherein the sensed motional activity in all receptacles is detected at once, i.e. in parallel. However, it is likewise conceivable that the sensed motional activity is detected in sequence, for instance one receptacle after the other.

[0133] It is furthermore preferred that the radiation device and the detection device, are configured for an auto-alignment with the sensor element. Said auto-alignment is preferably provided by automation components such as dedicated software, mechatronic and optomechanic hardware provided on these components.

[0134] Additionally or alternatively, the interrogation unit is preferably at least partially connected to and / or aligned with at least one positioning element of the frame, in particular in a region of the aperture of the frame. Additionally or alternatively, the interrogation unit is preferably at least partially received in at least one receiving cavity of the frame.

[0135] That is, and as mentioned earlier, the frame preferably comprises at least one positioning element that is configured to connect to and / or align with the interrogation unit. Additionally or alternatively, the frame preferably comprises at least one receiving cavity configured to at least partially receive the interrogation unit.

[0136] For the sake of completeness, it is noted again that a plurality of receptacles can be provided that are insertable into a plurality of apertures of the frame, and in which case it is preferred that a plurality of interrogation units and thus of positioning elements and / or receiving cavities are provided as well.

[0137] As mentioned earlier, the interrogation unit preferably comprises a detection device and a radiation device.

[0138] By arranging the interrogation unit(s), in particular the detection device(s) and the radiation device(s) at least partially in the receiving cavity(s) of the frame, a compact system integration is achieved.

[0139] The interrogation unit(s), in particular the detection device(s) and the radiation device(s), are preferably miniaturized, i.e. of a compact size and / or having a reduced form factor. As mentioned earlier, the radiation device preferably is an optical radiation device, and thus preferably is a miniaturized optical radiation device such as a laser diode or LED. The detection device preferably is an optical detection device and thus preferably a miniaturized optical detection device such as a photodetector or a micro-spectrometer.

[0140] The interrogation unit(s), in particular the detection device(s) and the radiation device(s) are preferably part of an interrogation device. The interrogation device preferably comprises a supporting frame on and / or in which the interrogation unit(s) are arranged. The supporting frame preferably has a flat shape such as plate-like shape, for instance of a rectangular or squared form.

[0141] The supporting frame is preferably connectable to the frame comprising the at least one aperture into which the receptacle comprising the sensor element is received. In particular, the supporting frame is preferably configured to be at least partially inserted into the frame. In other words, the frame may function as a cover or lid for the supporting frame, surrounding the supporting frame at least on its top side and at least partially along its lateral sides when assembled. To ensure proper positioning and orientation during assembly, the frame and the supporting frame may each comprise one or more alignment elements, such as recesses, protrusions, notches, or other geometrical features, formed for instance on corresponding sides. These alignment elements serve to guide the frame into a predefined orientation relative to the supporting frame during insertion, thereby preventing incorrect assembly and ensuring a secure and repeatable connection.

[0142] The supporting frame preferably comprises or consists of the same material as the frame.

[0143] The supporting frame and the frame, when assembled, in particular upon insertion of the supporting frame into the frame, can be seen as a chassis, i.e. the frame at least partially surrounds the supporting frame, providing structural support and ensuring proper alignment between the two components. This configuration facilitates a compact and stable assembly of the chassis.

[0144] Additionally, or alternatively, it is conceivable that the arrangement, in particular its frame, comprises at least one alignment element such as a V-groove that can align with a corresponding alignment element provided on the detection device and / or the radiation device in a mechanical manner.

[0145] The apparatus can comprise further components such as a fluid handling device configured to supply and / or remove fluids such as sample fluids or drugs from the device, in particular from the receptacle.

[0146] The apparatus can further comprise at least one heating element being configured to heat at least one of: the frame, the device, the receptacle, a sample received in the receptacle, or a fluid received in the receptacle. Additionally, or alternatively, the apparatus can comprise at least one cooling element being configured to cool at least one of: the frame, the device, the receptacle, a sample received in the receptacle, or a fluid received in the receptacle. Additionally, or alternatively, the apparatus can comprise at least one heating- cooling-element being configured to heat and cool at least one of: the frame, the device, the receptacle, a sample received in the receptacle, or a fluid received in the receptacle.

[0147] The heating element and / or the cooling element and / or the heating-cooling-element is preferably formed separately from the arrangement and is configured to contact the arrangement, in particular at least one of the frame, the device, the receptacle and / or being at least partially inserted into the receptacle. For example, a heating element in the form of a heating block could be provided, and wherein the device such as the frame is arranged on said heating block. Various heating elements are conceivable such as resistive heating elements or thermoelectric heating elements, e.g. Peltier elements, air fans or the like. Various cooling elements are conceivable such as thermoelectric cooling elements, e.g. Peltier elements. Various heating-cooling-elements are conceivable such as thermoelectric heating-cooling-elements, e.g. Peltier elements. The heating element and / or the cooling element and / or the heating-cooling-element can be configured and arranged such, that it heats and / or cools the entire arrangement or just part thereof, in particular just the receptacle.

[0148] It is furthermore preferred that the heating element and / or the cooling element and / or the heating-cooling-element is in connection with at least one temperature control device that control the heating and / or cooling.

[0149] It is furthermore preferred that the arrangement, for instance the receptacle, comprises at least one temperature sensing element being configured to sense a temperature of the receptacle and / or of a sample or fluid received within the receptacle.

[0150] In another aspect, a method of producing a device for sensing a motional activity of a particle is provided. The device preferably corresponds to the device as described above. The method comprises the steps of i) providing at least one receptacle configured to receive a sample comprising at least one particle, and ii) providing at least one sensor element being configured to sense a motional activity of the particle. The sensor element is integrated into the receptacle. The receptacle is at least partially insertable into at least one aperture of a frame. The device comprises at least one carrier element that is configured to hold the receptacle. The carrier element is configured to deform upon insertion of the receptacle into the aperture of the frame.

[0151] Any statements made herein regarding the method of producing the device preferably likewise apply to the device as such and vice versa.

[0152] The sensor element can be automatically integrated into the receptacle, preferably via a robotic arm of a robotic handling assembly. The automatic, in particular robotic, integration of the sensor element into the receptacle enables an exact xy positioning, e.g. with tolerances in the micrometer range. The robotic arm can directly attach the sensor element to an inner side of the receptacle. Alternatively, the robotic arm can attach the sensor element to the holding element and then attach the holding element to the inner side of the receptacle. In the event of the device comprising a plurality of receptacles it is preferred that the robotic arm integrates a plurality of sensor elements, optionally while being attached to the holding elements, into the receptacles, for instance via a so-called "pick & place".

[0153] To this end it is particularly preferred that all manufacturing steps are carried out automatically, in particular via the robotic arm. For instance, the robotic arm can attach the sensor element and / or the holding element to the inner side of the receptacle by chemical bonding such as gluing, wherein the robotic arm can comprise one or more glue nozzles that dispense droplets of glue into the receptacles and then picks and places the sensor elements and / or the holding elements onto the glue.

[0154] The sensor element can be at least regionally functionalized before or after being integrated into the receptacle. Different functionalization techniques are conceivable. For instance, the sensor element(s) can be at least regionally functionalized via dip coating as it is receptacle- known in the art.

[0155] The device is preferably manufactured under sterile conditions. As a result, the device, in particular its receptacle(s) and integrated sensor element(s), are sterile as receptacle.

[0156] In another aspect, a method of analyzing a motional activity of a particle with the apparatus as described above is provided. The method comprises the steps of i) at least partially inserting the at least one receptacle in the at least one aperture of the frame, ii) providing at least one sample comprising at least one particle in the at least one receptacle of the device, iii) sensing the motional activity of the particle with the sensor element, iv) optionally detecting the motional activity sensed by the sensor element with the detection device and generating at least one detection signal, and v) analyzing the sensed motional activity, in particular analyzing the at least one detection signal, with the analyzing unit.

[0157] Any statements made herein regarding the device as such, the apparatus comprising the arrangement or the method of manufacturing the device preferably likewise apply to the method of analyzing the motional activity with the apparatus and vice versa.

[0158] In the event of a plurality of receptacles comprising a plurality of sensor elements, the motional activity of particles can be sensed and detected simultaneously.

[0159] To this end it is particularly preferred that a plurality of receptacles are at least partially inserted into a plurality of apertures of the frame, wherein a plurality of same or different samples are provided in the plurality of receptacles, and wherein the motional activity of the plurality of sensor elements are preferably sensed individually and / or in parallel.

[0160] BRIEF DESCRIPTION OF THE DRAWINGS

[0161] Preferred embodiments of the invention are described in the following with reference to the drawings, which are for the purpose of illustrating the present preferred embodiments of the invention and not for the purpose of limiting the same. In the drawings,

[0162] Fig. 1 shows an exploded view of an analyzing apparatus comprising a device for sensing the motional activity of particles that comprises a plurality of receptacles and a plurality of sensor elements, a frame configured to receive the receptacles, and an interrogation device comprising interrogation units that are configured to interrogate the sensor according to the invention;

[0163] Fig. 2 shows a partial sectional view of the apparatus according to figure 1 ;

[0164] Fig. 3 shows a sectional view of receptacle of the device according to figure 1 ;

[0165] Fig. 4 shows a perspective view of a carrier element comprising a plurality of receptacles of a device for sensing a motional activity of a particle on a frame;

[0166] Fig. 5 shows a sectional view of the carrier element comprising the receptacles according to figure 4 on the frame;

[0167] Fig. 6 shows a sectional view of a receptacle comprising a sensor element and a cover element comprising a fluid channel of a device for sensing a motional activity of a particle;

[0168] Fig. 7 shows a sectional view of the carrier element comprising a plurality of receptacles comprising sensor elements and a cover element comprising a fluid channel of a device for sensing a motional activity of a particle;

[0169] Fig. 8 shows another sectional view of a receptacle comprising a sensor element and a cover element comprising a fluid channel of a device for sensing a motional activity of a particle;

[0170] Fig. 9 shows another sectional view of the carrier element comprising a plurality of receptacles comprising sensor elements and a cover element comprising a fluid channel of a device for sensing a motional activity of a particle;

[0171] Fig. 10 shows a perspective view of a sensor element comprising a flexible support;

[0172] Fig. 11 shows a perspective view of another sensor element comprising a plurality of flexible supports;

[0173] Fig. 12 shows a perspective view of another sensor element comprising a plurality of flexible supports;

[0174] Fig. 13 shows a partial top view of a sensor element comprising a flexible support and a sensor-alignment-element;

[0175] Fig. 14 shows a partial top view of another sensor element comprising a flexible support and sensor-alignment-elements;

[0176] Fig. 15 shows a partial side view of a sensor element comprising a flexible support comprising a reflective element;

[0177] Fig. 16 shows a partial side view of another sensor element comprising a flexible support comprising a reflective element;

[0178] Fig. 17 shows a top view of a sensor element being arranged on a holding element that comprises holding-alignment-elements; Fig. 18 shows a top view of a sensor element being arranged on another holding element that comprises holding-alignment-elements;

[0179] Fig. 19 shows a partial side view of a sensor element being arranged on a holding element;

[0180] Fig. 20 shows a top view of a receptacle comprising a sensor element being arranged on a holding element that comprises a recess and an uncovered part;

[0181] Fig. 21 shows a sectional view of a receptacle comprising a sensor element being arranged on a holding element that comprises a recess and an uncovered part;

[0182] Fig. 22 shows a partial exploded sectional view of a receptacle comprising a sensor element that is to be arranged on a holding element;

[0183] Fig. 23 shows a partial exploded sectional view of another receptacle comprising a sensor element that is to be arranged on an inner side of the receptacle;

[0184] Fig. 24 shows different manufacturing steps of arranging a sensor element on an inner side of a receptacle;

[0185] Fig. 25 shows a sectional view of another receptacle comprising a sensor element being arranged on an inner side of a receptacle;

[0186] Fig. 26 shows a sectional view of another receptacle comprising a sensor element being arranged on an inner side of a receptacle;

[0187] Fig. 27 shows a sectional view of another receptacle comprising a sensor element being arranged on a holding element in a receptacle;

[0188] Fig. 28 shows a sectional view of another receptacle comprising a sensor element being arranged on an inner side of a receptacle;

[0189] Fig. 29 shows a sectional view of another receptacle comprising a sensor element that is to be arranged on an inner side of a receptacle;

[0190] Fig. 30 shows a sectional view of another receptacle comprising a sensor element being stabilized by a stabilizing element of a sealing element;

[0191] Fig. 31 shows different manufacturing steps of arranging a sensor element on a holding element in a receptacle;

[0192] Fig. 32 shows different manufacturing steps of arranging another sensor element on a holding element in a receptacle;

[0193] Fig. 33 shows a partial sectional view of a sensor element and a detection device configured to detect a motional activity sensed by the sensor element;

[0194] Fig. 34 shows another partial sectional view of the sensor element according to figure 33;

[0195] Fig. 35 shows another partial sectional view of the sensor element according to figure 33; Fig. 36 shows a partial sectional view of a sensor element being arranged on an inclination of a receptacle;

[0196] Fig. 37 shows a partial sectional view of a sensor element being arranged in a receptacle comprising a port;

[0197] Fig. 38 shows a partial sectional view of another sensor element being arranged on an inclination of a receptacle;

[0198] Fig. 39 shows a top view of a sensor element being arranged on an inner side of a receptacle;

[0199] Fig. 40 shows a top view of another sensor element being arranged on an inner side of another receptacle;

[0200] Fig. 41 shows a partial sectional view of a receptacle comprising a sensor element that comprises functionalizations;

[0201] Fig. 42 shows a top view of another sensor element comprising a functionalization;

[0202] Fig. 43 shows another top view of another sensor element comprising a functionalization;

[0203] Figs. 44-

[0204] 53 show side views of other sensor elements comprising functionalizations;

[0205] Fig. 54 shows a graph depicting the motional activity of particles that has been analyzed with an apparatus according to the invention.

[0206] DESCRIPTION OF PREFERRED EMBODIMENTS

[0207] Various aspects of a device 1 , of an arrangement 100 comprising the device 1 and a frame 45, and of an analyzing apparatus 1000 comprising the arrangement 100 configured to analyze a motional activity of a particle are illustrated with respect to the figures.

[0208] As follows from figures 1 and 2, the device 1 comprises a carrier element 24 with a plurality of receptacles 2, 2a, ... being held on a carrier element 24. In particular, and as follows from figures 4 and 5, the receptacles 2, 2a, ... are formed separately from the carrier element 24 and are inserted into receiving openings 38, 38a, 38b, 38c... formed in the carrier element 24 and on demand, i.e. according to a particular need.

[0209] The receptacles 2, 2a, ... are insertable into apertures 46, 46a, ... of the frame 45. The carrier element 24 is compliant and configured to deform upon insertion of the receptacles 2, 2a, ... into the apertures 46, 46a, ... of the frame 45. As follows from figure 1 , the carrier element 24 has a flat shape and extends primarily along a first and second orthogonal dimensions D1 ; D2 and to a lesser extend along a third dimension D3 perpendicular to said first and second dimensions D1 ; D2. Said first and second dimensions D1 ; D2 can be referred to as a length and a width of the carrier element 24, which are preferably larger than the third dimension D3 being a depth or thickness of the carrier element 24. In the depicted examples, the carrier element 24 is in the form of a rectangular strip or plate.

[0210] As best seen in figures 1 and 2, the receptacles 2, 2a, ... extend along the third dimension D3 or the depth or thickness of the carrier element 24, respectively, and protrude from a bottom side 54 of the carrier element 24. That is, a length of the receptacles 2, 2a, ... along this third dimension D3 is greater than the length or the thickness of the carrier element 24.

[0211] The receptacles 2, 2a, ... comprise in each case a top side 12 and an opposite bottom side 13. The bottom side 13 of the receptacle protrudes from the bottom side 54 of the carrier element 24 and the top side 12 of the receptacle 2, 2a, ... protrudes in the depicted example from the top side 55 of the carrier element 24.

[0212] The receptacles 2, 2a, ... extends entirely through the carrier element 24 with respect to the third direction D3 and the receiving openings 38, 38a, ... of the carrier element 24 in which the receptacles 2, 2a, ... are received are through-openings.

[0213] The carrier element 24 and the frame 45 are separate components, i.e., individual parts, wherein the carrier element 24 can be arranged on the frame 45, in particular on a top side 56 of the frame 45, and can be removed from the frame 45 as needed.

[0214] That is, the frame 45 comprises a top side 56 and an opposite bottom side 57. The apertures 46, 46a, ... of the frame 45 extend from the top side 56 of the frame 45 at least partially towards the bottom side 57 of the frame 45. Upon insertion of the receptacles 2, 2a, ... into the apertures 46, 46a, ... of the frame 45, the bottom side 54 of the carrier element 24 is arranged on the top side 56 of the frame 45.

[0215] At least one aperture 46 of the frame 45 comprises at least one aperture-receptacle- alignment element 50 and at least one receptacle 2 comprises at least one receptacle- aperture-alignment element 51 that align the receptacle 2 with respect to the frame 45 upon insertion of the receptacle 2 into the aperture 46 of the frame 45, see figure 2. In fact, the aperture-receptacle-alignment element 50 and the receptacle-aperture-alignment element 51 are complementary to one another and are in each case provided by means of an asymmetric shape of the particular aperture 46 and the receptacle 2. Said asymmetric shapes, i.e. the aperture-receptacle-alignment element 50 of the aperture 46 and the receptacle-aperture-alignment 51 of the receptacle 2 are provided here in each case by means of an inclined wall 58; 59 of otherwise flat walls. That is, the aperture 46 comprises an aperture-receptacle-alignment element 50 in the form of a conically tapered wall 58, and the receptacle 2 correspondingly comprises a receptacle-aperture-alignment element 51 in the form of a matching conically tapered wall 59, such that the receptacle 2 is guided into a predefined position during insertion of the receptacle 2 into the aperture 46.

[0216] The frame 45, in the regions of the apertures 46, 46a, ... , comprises receiving cavities 53, 53a, ... configured to at least partially receive interrogation units 48, 48a, ... configured to interrogate the sensor elements 3, 3a, ....

[0217] The interrogation units 48, 48a, ... comprise in each case a detection device 30, 30a, ... in the form of miniaturized optical detection devices such as photodetectors or microspectrometers and a radiation device 31 , 31a, ... in the form of miniaturized optical radiation devices such as laser diodes or LEDs.

[0218] The interrogation units 48, 48a, ... , i.e. the detection devices 30, 30a, ... and the radiation devices 31 , 31a, ... , are part of an interrogation device 47. The interrogation device 47 comprises a supporting frame 49 on and in which the interrogation units 48, 48a, ... are arranged. In particular, the supporting frame 49 comprises a plurality of openings 60, 60a, ... into which the interrogation units 48, 48a, ... are partially inserted while protruding from a top side 61 of the supporting frame 49. The supporting frame 49 has a flat shape, in particular a plate-like shape of a rectangular form corresponding to the form of the frame 45.

[0219] The supporting frame 49 is partially inserted into the frame 45., wherein the frame 45 covers the supporting frame 49 on its top side 61 and along its lateral sides 62 when assembled. To ensure proper positioning and orientation during assembly, the frame 45 and the supporting frame 49 in each case comprise an alignment element 63; 64 here in the form of a recess formed in a corner region 65; 66 of the frame 45 and the supporting frame 49, respectively. These alignment elements 63; 64 serve to guide the frame 45 into a predefined orientation relative to the supporting frame 49 during insertion of the supporting frame 49 into the frame 45.

[0220] In the assembled state of the frame 45 and the supporting frame 49, the interrogation units 48, 48a, ... are arranged in a region of the apertures 46, 46a, ... of the frame 45. In particular, the receiving cavities 53, 53a, ... of the frame 45 can merge into the apertures 46, 46a, ... of the frame 45. That is, one cavity 53, 53a, ... and one aperture 46, 46a, ... of the frame form in each case a passage opening 67, 67a, ....

[0221] Furthermore, the frame 45 in a region of the apertures 46, 46a... as well as in the regions of the receiving cavities 53, 53a, ... comprises positioning elements 52, 52a, .. configured to align the interrogation units 48, 48a, .... In the depicted example, the positioning elements 52, 52a, ... are sockets and serve the purpose of defining a precise location for the positioning of the interrogation units 48, 48a, ... on the frame.

[0222] As follows from figures 1 and 2, the detection devices 30 and the radiation devices 31 are located outside of the receptacles 2, 2a, .... Moreover, the detection devices 30 and the radiation devices 31 are located with respect to a same side of the receptacles 2, 2a,... , here with respect to the bottom side 13 of the receptacles 2, 2a, ... .

[0223] In the embodiment depicted in figures 3-to 5, lateral sides 15 of the receptacle 2 are tapering inwards when seen from a top side 12 of the receptacle 2 towards a bottom side 13 of the receptacle 2. Moreover, various shapes of the receptacle 2 are conceivable. For instance, when seen in cross-section, a shape of the receptacle 2 at least in a region of the bottom side 13 of the receptacle 2 is circular, see e.g. figures 1 to 5 and 39, or elliptical, see figure 40.

[0224] As furthermore follows from these figures, a plurality of the receptacles 2, 2a, ... comprise in each case a sensor element 3, 3a, ... being configured to sense a motional activity of the particle, wherein said sensor elements 3, 3a, ... are in each case integrated into the respective receptacle 2, 2a, .... To this end two ways of integration are possible, either an integration in the form of a direct attachment of the sensor element 3 to the receptacle 2 such as a bottom side 13 of the receptacle 2, see e.g. figures 5 to 9, or an integration in the form of an indirect attachment of the sensor element 3 to the receptacle 2 via a holding element 4, see e.g. figures 3 and 19 to 23. As follows from figures 4 to 9, the receptacles 2, 2a, ... can be covered with at least one cover element 26. In the embodiments of figures 4 and 5, the receptacles 2, 2a, ... are covered with individual cover elements 26, 26a, ... , whereas in the embodiments of figure

[0225] 7 and 9, several receptacles 2, 2a, ... share a common cover element 26. The cover elements 26 depicted in figures 6 to 9 comprise at least one inlet 27 for introducing fluids into the receptacle 2 as well as at least one outlet 28 for removing fluids out of the receptacle 2. Furthermore, a fluid channel 29 is present that provides a fluid connection between the inlet 27 and the outlet 28.

[0226] The sensor elements 3 comprises at least one flexible support 5 being configured to oscillate due to a motional activity of the particle. In figures 3, 6 to 21 , 33 to 41 , and 45, 47, 49, 51 and 53 for instance, the flexible support 5 is a cantilever. In figures 42, for instance, the flexible support 5 is a membrane such as a graphene drum. In figures 44, 46, 48, 50 and 52, for instance, the flexible support 5 is a bridge.

[0227] As follows from figures 10 to 12, the sensor element 3 can comprise a single flexible support (figure 10) or two or more flexible supports 5, 5a, ... (figures 11 and 12). Said two or more flexible supports 5, 5a, ... can be arranged in an array and on one lateral side 6 (figure 11) or on two or more lateral sides 6, 6a, ... of the sensor element 3 (figure 12). As furthermore follows from these figures, the sensor element 3 comprises a sensor body 7 in the form of a chip or a die, and wherein the flexible support(s) 5, 5a, ... are attached to or are integrally formed on the sensor body 7.

[0228] Figures 15 and 16 depict a flexible support 5 that comprises at least one reflective element

[0229] 8 configured to reflect incident electromagnetic radiation in the form of a reflective coating. In the depicted examples, the reflective element 8 extends partially along the flexible support 5, in particular on a top side 10 of the flexible support 5 facing away from a bottom side 13 of the receptacle 2 (figure 15) or on a bottom side 11 of the flexible support 5 facing a bottom side 13 of the receptacle 2 (figure 16).

[0230] As mentioned initially, the sensor element 3 can be integrated into the receptacle 2 via a direct attachment to an inner side 14 of the receptacle 2 or via an indirect attachment to an inner side 14 of the receptacle 2 via at least one holding element 4 being attached to the sensor element 3 and to the inner side 14 of the receptacle 2.

[0231] Figures 17 to 22 and 31 to 32 depict sensor elements being attached to holding elements 4, in particular onto a top surface 39 of the holding elements 4. A bottom surface 40 of the holding elements 4 is in turn attached to an inner side 14 of the receptacle 2. As follows from figures 13 and 14, the sensor element 3 can comprise at least one sensor-alignment- element 16 that aligns the sensor element 3 with respect to the receptacle 2 and / or with respect to the holding element 4. Here, the sensor-alignment-element 16 is a recess or opening being formed in the sensor element 3 that can be aligned with respect to a counterpart receptacle-alignment-element 33 of the receptacle, see e.g. figure 31 , and / or with respect to a counterpart holding-alignment-element 17 of the holding element 4, see e.g. figures 17 and 18. In particular, the receptacle-alignment-element 33 is provided here in the form of a protrusion or post formed in the receptacle 2 and the holding-alignment- element 17 is a recess or opening being formed in the holding element 4.

[0232] As best seen in figure 19, the holding element 4 can at least partially surround the sensor element 3 and form a pocket 41 , whereby the holding element 4 protects the sensor element 3 from mechanical influences. Moreover, the sensor element 3, in particular the flexible support 5, is located at a distance from a bottom side 13 of the receptacle 2, wherein a gap 18 is formed between the bottom side 13 of the receptacle 2 and the sensor element 3, in particular the flexible support 5. Said gap 18 is provided by the holding element 4.

[0233] As furthermore follows from these figures and from figure 20, the holding element 4 extends only partially along the bottom side 13 of the receptacle 2 and leaves at least one uncovered part 19 on the bottom side 13 of the receptacle 2. The sensor element 3 is arranged on the holding element 4 in such a way that the sensor element 3, in particular the flexible support

[0234] 5, extends at least partially over the uncovered part 19 of the holding element 4. In the present case, the uncovered part 19 is provided by a recess 20 of the holding element 4, and wherein the flexible support 5 is partially arranged in a region of said recess 19. As indicated in figure 21 , said uncovered part 19 and / or said recess 20 define a sub-volume Vs or a first volume level of a total volume Vt defined by the receptacle.

[0235] Figures 24 to 29 illustrate various possibilities of directly or indirectly attaching the sensor element 3 to the receptacle 2. In fact, figures 24 and 25 illustrates a direct attachment of the sensor element 3 to an inner side 14 of the receptacle 2, here to the bottom side 13, via gluing with at least one glue 34. Gluing can enhance the mechanical stability over storage, transport and the measurements. The glue composition may vary with respect to the receptacle material and the sensor element material to obtain strong binding force. Figures 26 and 27 illustrate a direct and indirect attachment of the sensor element 3 to the inner side 14 of the receptacle 2 via press joining. That is, the sensor element 3 or the holding element 4 can be attached by a pressing process that likewise enhances a mechanical stability over storage, transport and measurements, however without any external chemicals that need to be added to the receptacle 2 as it is the case with the gluing. As illustrated in figure 26, in press joining, the sensor element 3 is pressed directly into the receptacle 2 creating strong mechanical fixation by applying forces F in directions presented by arrows.

[0236] Figure 28 illustrates a direct attachment of the sensor element 3 to the inner side 14 of the receptacle 2 via electrostatic sealing, wherein the sensor element 3 is electrochemically attached to the inner side 14 with the help of voltage applied by two electrodes 35, whereby the sensor element 3 is bonded directly into the receptacle 2 creating strong mechanical fixation.

[0237] Figure 29 illustrates a direct attachment of the sensor element 3 to the inner side 14 of the receptacle 2 via corresponding mounting interfaces 36 and 37 that are provided on the sensor element 3 and the inner side 14 of the receptacle 2, respectively. Here, said mounting interfaces correspond to a recess or groove 37 formed in a bottom side 11 of the sensor element 3 that can engage a corresponding protrusion or notch 36 formed on the bottom side 13 of the receptacle 2. That is, the mounting interfaces correspond to mechanical interface structures that enable a mechanical positioning and attachment of the sensor element 3, wherein the sensor element 3 is pressed directly into the receptacle 2, thereby creating a strong mechanical fixation based on mechanical / topological features designed both in the receptacle 2 and the sensor element 3. The arrow in figure 29 indicates a direction of the applied force to create the fixation.

[0238] Figures 30 to 32 depict sensor elements 3 being stabilized with stabilizing elements 22; 32. In a first variant depicted in figure 30, the stabilizing element 22 is arranged removably in the receptacle 2 and can be removed before using the device 1 for sensing the particle. In particular, the stabilizing element 22 is in connection with a removable sealing element 23 that seals the receptacle 2 towards the outside. Here, the stabilizing element 22 is a pin that protrudes from a bottom side 42 of the sealing element 23 facing an inside of the receptacle 2 and that extends into the receptacle 2 to the sensor element 3 being arranged at the bottom side 13 of the receptacle 2. A free end 43 of the stabilizing element 22 presses against the sensor element 2. In a second variant depicted in figures 31 and 32, the stabilizing elements 32 are permanently arranged in the receptacle 2. Here, said stabilizing elements 32 have the shape of a pin or plate that is glued or otherwise attached to the receptacle 2 and the sensor element 3. Said stabilizing elements 32 also serve the purpose of aligning the receptacle 2 with the sensor element 3 and can at the same time also provide the receptacle-alignment-element 33 mentioned earlier, i.e. the counterpart alignment element to the sensor-alignment-element 16. For example, figure 31 illustrates that the receptacle-alignment-elements 33 can also be a stabilizing element 32 if, for example, they are melted down. Figure 32 illustrates a stabilizing element 32 in the form of a plate that presses against the sensor element 3.

[0239] Figures 33 to 38 illustrate various arrangements of the sensor element 3 within the receptacle 2 as well as various conceivable designs of the receptacles 2. For instance, and as illustrated in figures 33 to 36, at least part of the receptacle 2 such as here the bottom side 13 of the receptacle 2 and / or a lateral side 15 of the receptacle 2 can be transparent or translucent and thereby allow the transmission of electromagnetic radiation that is emitted from a radiation device 31 and that is to be detected with a detection device 30 being located outside of the receptacle 2.

[0240] As follows from figure 33, the particular design and arrangement of the sensor element 3 within the receptacle 2 defines a cavity 44 that can serve as an interferometric cavity, allowing a detection of the sensed motion with a detection device 30 in the form of an interferometer. In fact, and as follows from figure 33, an interferometer head 30 can be located close to the bottom side 13 of the receptacle 2 and thus close to the interferometric cavity 44.

[0241] Moreover, a side such as here a bottom side 13 of the receptacle 2 can be straight (see figures 33 to 35) or can be at least regionally inclined and form at least one inclination 21 (see figures 36 and 38). Consequently, the sensor element 3, in particular the flexible support 5, can be arranged parallel to a side such as here the bottom side 13 of the receptacle 2 (see figures 33 to 35), or can be arranged inclined in the receptacle 2 (see figures 36 and 38).

[0242] Furthermore, and as illustrated in figure 37, the receptacle 2 can comprise at least one port 25 configured to inlet at least one fluid into the receptacle 2 and / or to outlet at least one fluid out of the receptacle 2. Here, said port 25 is provided in a region of a bottom side 13 of the receptacle 2. Figures 39 to 53 illustrate different functionalizations of the sensor element 3. That is, the sensor element 3, in particular the flexible support 5, can be at least regionally functionalized with at least one functionalization 9. Said functionalization 9 can enhance an attachment of the particle to the sensor element 3. As follows from these figures, the functionalization 9 can be provided on a top side 10 of the sensor element 3, in particular on the top side of the flexible support 5, facing away from the bottom side 13 of the receptacle 2 (see figure 41). Additionally, or alternatively, the functionalization 9 can be provided on a bottom side 11 of the sensor element 3, in particular on the bottom side 11 of the flexible support 5, facing the bottom side 13 of the receptacle (see figure 41). Moreover, the functionalization 9 can extend only partially along the flexible support 5 (see figures 41 to 49) or along the entire flexible support 5 (see figures 50 to 53).

[0243] The graph depicted in figure 54 illustrates that the device 1 and apparatus 1000 according to the invention can be used to perform antibiotic susceptibility testing (AST). In fact, said example concerns bacteria attached to a sensor element 3 in the form of a Si / SiO2 cantilever in a plastic device 1 comprising receptacles 2, 2a, ... made of polystyrene. The figure shows oscillations sensed by the sensor element 3 at different points in time, in fact before an attachment of the particles to the sensor element 3, after the attachment of the particles to the sensor element 3, and ultimately after the supply of a drug into the receptacle 2. In particular, the sensor element 3 in the form of the cantilever with attached Escherichia coli ATCC-25922 was measured in 50% (v / v) lysogenic broth culture medium for 30 minutes and was subsequently exposed to inhibitory concentrations of the antibiotic meropenem for 90 min (2 pg / ml). The sensed motional activity of the cantilever 3 was detected with an interrogation device in the form of an optical readout system consisting of an SLED 31 and a photodetector 30 that was used to detect the oscillations at a 60kHz frequency. The detected signals were then analyzed with an analysis unit that performed an analysis as described in the patent application of Jozwiak et al., Method of analyzing the motional activity of particles, PCT / EP2023 / 055596, WO2023174728A1. As follows from this graph, the trend of the variance upon exposure to meropenem is negative as expected when bacterial viability decreases. LIST OF REFERENCE SIGNS

[0244] 1 device

[0245] 2 receptacle

[0246] 3 sensor element

[0247] 4 holding element

[0248] 5 flexible support

[0249] 6 lateral side of sensor element

[0250] 7 sensor body

[0251] 8 reflective element

[0252] 9 functionalization

[0253] 10 top side of sensor element

[0254] 11 bottom side of sensor element

[0255] 12 top side of receptacle

[0256] 13 bottom side of receptacle

[0257] 14 inner side of receptacle

[0258] 15 lateral side of receptacle

[0259] 16 sensor-alignment-element

[0260] 17 holding-alignment-element

[0261] 18 gap

[0262] 19 uncovered part

[0263] 20 recess

[0264] 21 inclination

[0265] 22 stabilizing element

[0266] 23 sealing element

[0267] 24 carrier element

[0268] 25 port

[0269] 26 cover element

[0270] 27 inlet

[0271] 28 outlet

[0272] 29 fluid channel

[0273] 30 detection device

[0274] 31 radiation device

[0275] 32 stabilizing element

[0276] 33 receptacle-alignment-element

[0277] 34 glue 35 electrode

[0278] 36 mounting interface

[0279] 37 mounting interface

[0280] 38 receiving opening

[0281] 39 top surface

[0282] 40 bottom surface

[0283] 41 pocket

[0284] 42 bottom side

[0285] 43 free end

[0286] 44 cavity

[0287] 45 frame

[0288] 46 aperture

[0289] 47 interrogation device

[0290] 48 interrogation unit

[0291] 49 supporting frame

[0292] 50 aperture-receptacle-alignment element

[0293] 51 receptacle-aperture-alignment element

[0294] 52 positioning element

[0295] 53 receiving cavity

[0296] 54 bottom side of carrier element

[0297] 55 top side of carrier element

[0298] 56 top side of frame

[0299] 57 bottom side of frame

[0300] 58 inclined wall aperture

[0301] 59 inclined wall receptacle

[0302] 60 opening

[0303] 61 top side of supporting frame

[0304] 62 lateral side of supporting frame

[0305] 63 alignment element

[0306] 64 alignment element

[0307] 65 corner region

[0308] 66 corner region

[0309] 100 arrangement

[0310] 1000 analyzing apparatus Vs sub-volume

[0311] Vt total volume D1 first dimension

[0312] D2 second dimension

[0313] D3 third dimension

Claims

44CLAIMS1 . A device (1) for sensing a motional activity of a particle comprising:- at least one receptacle (2) configured to receive a sample comprising at least one particle, and- at least one sensor element (3) being configured to sense a motional activity of the particle, wherein the sensor element (3) is integrated into the receptacle (2), wherein the receptacle (2) is at least partially insertable into at least one aperture (46) of a frame (45), characterized in that the device (1) comprises at least one carrier element (24) that is configured to hold the receptacle (2), and wherein the carrier element (24) is configured to deform upon insertion of the receptacle (2) into the aperture (46) of the frame (45).

2. The device (1) according to claim 1 , wherein the carrier element (24) is compliant and / or configured to undergo a shape change and / or to elastically deform, and / or wherein the carrier element (24) comprises or consists of at least one polymer, preferably at least one thermoplastic polymer such as a thermoplastic elastomer (TPEs), low-density polyethylene (LDPE), ethylene-vinyl acetate (EVA), thermoplastic polyurethane (TPU), or polypropylene (PP), and / or at least one metal compound and / or an alloy such as a metal alloy, for instance steel.

3. The device (1) according to any one of the preceding claims, wherein the receptacle (2) is at least one of rigid, stiff, or non-deformable, and / or wherein the receptacle (2) and the carrier element (24) are a single-piece element or separate components.

4. The device (1) according to any one of the preceding claims, wherein the sensor element (3) comprises at least one flexible support (5) being configured to oscillate due to a motional activity of the particle, the flexible support (5) preferably being a cantilever, a membrane such as a graphene drum, or a bridge.

5. The device (1) according to any one of the preceding claims, wherein the sensor element (3) comprises at least one sensor-alignment-element (16) that aligns the sensor45 element (3) with respect to the receptacle (2) and / or with respect to a holding element (4), and wherein the sensor-alignment-element (16) preferably is a recess or opening being formed in the sensor element (3), and / or wherein the sensor-alignment-element (16) is preferably aligned with respect to a counterpart receptacle-alignment-element (33) provided in the receptacle and / or a counterpart holding-alignment-element (17) provided on the holding element (4).

6. The device (1) according to any one of the preceding claims, wherein at least one of:- a side (13) of the receptacle (2) is straight or is at least regionally inclined and forms at least one inclination (21),- the sensor element (3), in particular the flexible support (5), is arranged parallel to a side (13) of the receptacle (2), or- the sensor element (3), in particular the flexible support (5), is arranged inclined in the receptacle (2).

7. The device (1) according to any one of the preceding claims, further comprising at least one cover element (26) that covers the receptacle (2), and wherein:- the cover element (26) seals the receptacle (2) in a liquid tight and / or gas tight manner towards an outside, and / or- the cover element (26) comprises at least one inlet (27) for introducing fluids into the receptacle (2) and / or at least one outlet (28) for removing fluids out of the receptacle (2), and / or- the cover element (26) comprises at least one fluid channel (29).

8. An arrangement (100) comprising:- at least one device (1) as claimed in any one of the preceding claims, and- at least one frame (45) comprising at least one aperture (46), wherein the receptacle (2) is preferably removably insertable into the aperture (46) of the frame (45), and wherein the device (1) preferably comprises a plurality of receptacles (2, 2a. ...) that are held by the at least one carrier element (24) and that are insertable into a plurality of apertures (46, 46a, ...) of the frame (45).

9. The arrangement (100) according to claim 8, wherein the frame (45) comprises or consists of at least one metal compound and / or at least one ceramic material, and / or46 wherein the frame (45) is rigid and / or thermally conductive and / or is heat-retaining.

10. The arrangement (100) according to claim 8 or 9, wherein the receptacle (2) and the aperture (46) are configured to enter a form-fit and / or a press-fit and / or force-fit upon insertion of the receptacle (2) into the aperture (46) of the frame (45), and / or wherein the aperture (46) of the frame (45) comprises at least one aperture- receptacle-alignment element (50) and / or the receptacle (2) comprises at least one receptacle-aperture-alignment element (51) that align the receptacle (2) with respect to the frame (45) upon insertion of the receptacle (2) into the aperture (46) of the frame (45).11 . The arrangement according to any one of claims 8 to 10, wherein the frame (45), in particular in a region of the aperture (46), comprise at least one positioning element (52) configured to connect to and / or align at least one interrogation unit (48) configured to interrogate the sensor element (3) with respect to the frame (45), in particular with respect to the aperture (46), and / or wherein the frame (45), in particular in the region of the aperture (46), comprises at least one receiving cavity (53) configured to at least partially receive an interrogation unit (48) configured to interrogate the sensor element (3).

12. An analyzing apparatus (1000) configured to analyze a motional activity of a particle comprising: at least one arrangement (100) as claimed in any one of claims 8 to 11 , and at least one analyzing unit configured to analyze the sensed motional activity of the particle, and optionally, further comprising at least one interrogation unit (48) configured to interrogate the sensor element (3), the interrogation unit (48) preferably comprising at least one detection device (30) and / or at least one radiation device (31), the detection device (30) preferably being configured to detect a motional activity sensed by the sensor element (3) and to transmit at least one detection signal being generated upon the detection of the sensed motional activity to the analyzing unit, the detection device (30) preferably being configured to detect an oscillation of the flexible support (5) due to a motional activity of the particle, and the radiation device (31) preferably being configured to irradiate electromagnetic radiation onto the sensor element (3).

13. The analyzing apparatus (1000) according to claim 12, wherein the interrogation unit(48), in particular the detection device (30) and / or the radiation device (31), is located outside of the receptacle (2), and / or wherein the interrogation unit (48), in particular the detection device (30) and / or the radiation device (31), is facing a bottom side (13) of the receptacle (2) or a lateral side (15) of the receptacle (2), and / or wherein the detection device (30) and the radiation device (31) are located with respect to a same side or a different side of the receptacle (2).

14. The analyzing apparatus (1000) according to claim 12 or 13, wherein the device (1) and / or the interrogation unit (48), in particular the detection device (30) and / or the radiation device (31), are immovable, and / or wherein the interrogation unit (48) is at least partially connected to and / or aligned with at least one positioning element (52) of the frame (45), in particular in a region of the aperture (46) of the frame (45), and / or wherein the interrogation unit (48) is at least partially received in at least one receiving cavity (53) of the frame (45).

15. A method of producing a device (1) for sensing a motional activity of a particle, preferably a device (1) as claimed in any one of claims 1 to 7, the method comprising the steps of:- Providing at least one receptacle (2) configured to receive a sample comprising at least one particle, and- Providing at least one sensor element (3) being configured to sense a motional activity of the particle, wherein the sensor element (3) is integrated into the receptacle (2), wherein the receptacle (2) is at least partially insertable into at least one aperture (46) of a frame (45), characterized in that the device (1) comprises at least one carrier element(24) that is configured to hold the receptacle (2), and wherein the carrier element (24) is configured to deform upon insertion of the receptacle (2) into the aperture (46) of the frame (45).

16. A method of analyzing a motional activity of a particle with the analyzing apparatus (1000) as claimed in any one of claims 12 to 14, the method comprising the steps of:- At least partially inserting the at least one receptacle (2) in the at least one aperture (46) of the frame (45);- Providing at least one sample comprising at least one particle in the at least one receptacle (2) of the device (1);- Sensing the motional activity of the particle with the sensor element (3), and- Optionally detecting the motional activity sensed by the sensor element (3) with the detection device (30) and generating at least one detection signal, and- Analyzing the sensed motional activity of the particle, in particular the at least one detection signal, with the analyzing unit.

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