Parallel probing of multiple samples in self-assembled structures

Abstract

Disclosed herein are methods for parallel probing of multiple samples, sensor chips for parallel probing of multiple samples, sensing devices for parallel probing of multiple samples, and measurement systems for parallel probing of multiple samples. The methods include providing a sensor chip, the sensor chip comprising a sensing layer disposed in or on a substrate, and a measurement volume adjacent to the sensing layer. The sensing layer comprises a plurality of sensing elements, each configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element. A carrier fluid including a plurality of sample objects is provided to the measurement volume, each of the sample objects comprising or forming a respective sample. The number of sample objects in the measurement volume is controlled such that the sample objects form a self-assembled structure in the measurement volume. A self-assembled structure is a structure in which the arrangement of the sample objects is at least partially defined by interactions between the sample objects themselves. Measurements are performed on one or more of the samples while the sample objects are disposed in the self-assembled structure, the measurements on the samples being performed using one or more sensing elements disposed adjacent to the respective sample objects in the self-assembled structure.

Description

[Technical field]

[0001] The present invention is in the field of chemical analysis and medical diagnostics. In particular, the present invention relates to a method for parallel probing of multiple samples, a corresponding sensor chip, a corresponding sensing device and a corresponding measurement system. [Background technology]

[0002] High-throughput parallel analysis of samples is essential for many applications in chemistry, life sciences, and medicine. Such experiments can be carried out, for example, on standardized microplates that typically comprise a rectangular array of wells for receiving samples, and their standardized well layout allows efficient processing of large numbers of samples using liquid handling robots.

[0003] To further increase throughput, microfluidic chips have been developed with multiple sample sites, such as microfluidic sample wells, which can provide and process samples simultaneously. Sample wells typically have a size on the order of 10 μm to 100 μm, which not only allows for multiple sample wells to be placed on a single chip, but also facilitates placing sensors in close proximity to the sample. Sensors can be integrated into the chip and configured to measure, for example, the temperature or electrical or magnetic properties of the sample, see, for example, C. Yang et al., IEEE Transactions on Biomedical Circuits and Systems, vol. 3, no. 3, pp. 160-168 (2009); H. Zhang et al., Anal. Chem. 2017, 89, 11, 5832-5839; and H. Zhang et al., npj Quantum Inf. 3:31 (2017). In other examples, samples can be probed by optical means, such as fluorescence spectroscopy.

[0004] However, while such microfluidic chips allow for rapid probing of many samples in parallel, the small size of the sample wells creates several challenges in manufacturing, and in particular in handling the chips. Microfluidic chips are prone to mechanical damage as well as contamination from previous samples, since it is nearly impossible to completely remove the sample from the sample well after a measurement. As a result, microfluidic chips are typically disposable products, making experiments costly and time-consuming, since a new chip needs to be attached and possibly realigned for each experiment. Furthermore, preparing the sample in the sample well is difficult due to the small length scales involved. Due to the small volume of the sample well, the sample may also evaporate during preparation and measurement, which may reduce the reliability of the measurement results. US Patent Application Publication No. 2019 / 0285579 discloses a fluorescent test system having a dielectrophoretic device with microwells in which a test object, such as a cell, can be placed above a corresponding photodiode. Using a pair of electrodes, the test object can be captured in one of the microwells by dielectrophoresis. A similar device is also known in US Patent Application Publication No. 2019 / 0250102. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] US Patent Application Publication No. 2019 / 0285579 [Patent Document 2] US Patent Application Publication No. 2019 / 0250102 [Non-patent literature]

[0006] [Non-Patent Document 1] C. Yang et al., IEEE Transactions on Biomedical Circuits and Systems, vol.3, no.3, pp.160-168(2009) [Non-Patent Document 2] H.Zhang et al.,Anal.Chem.2017,89,11,5832-5839 [Non-Patent Document 3] H. Zhang et al.,npj Quantum Inf.3:31(2017) Summary of the Invention

[0007] It is therefore an object of the present invention to simplify sample preparation and handling for high-throughput parallel probing of multiple samples on a microfluidic sensor chip.

[0008] This object is achieved by a method for parallel probing of multiple samples according to claim 1, a sensor chip for parallel probing of multiple samples according to claim 14, a sensing device for parallel probing of multiple samples according to claim 26 and a measurement system for parallel probing of multiple samples according to claim 35. Embodiments of the invention are detailed in the dependent claims.

[0009] A method for parallel probing of multiple samples according to the present invention includes providing a sensor chip, the sensor chip comprising a sensing layer disposed in or on a substrate, and a measurement volume adjacent to the sensing layer. The sensing layer comprises a plurality of sensing elements, each of which is configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element. A carrier fluid containing a plurality of sample objects is provided to the measurement volume, each of the sample objects comprising or forming a respective sample. The number of sample objects in the measurement volume is controlled such that the sample objects form a self-assembled structure in the measurement volume. Measurements are performed on one or more of the samples while the sample objects are disposed in the self-assembled structure, the measurements on the samples being performed using one or more sensing elements disposed adjacent to the respective sample objects in the self-assembled structure.

[0010] The sensor chip may comprise a single-layer or multi-layer substrate, and the measurement volume may be, for example, a recess in the top surface of the substrate or a hollow volume surrounded by the substrate. In addition, the sensor chip may comprise a microfluidic structure, such as an inlet channel and / or an outlet channel, in fluid communication with the measurement volume and providing a carrier fluid thereto. In some examples, the sensor chip may be a sensor chip according to any one of the embodiments of the present invention described herein, or a sensor chip of a sensing device according to any one of the embodiments of the present invention described herein.

[0011] Each of the sensing elements is configured to generate a sensor signal, e.g., an optical signal, a magnetic signal, and / or an electrical signal, that characterizes a physical observable in the vicinity of the sensing element, e.g., at the location of the sensing element, or within a sensing volume around the sensing element. In the context of the present disclosure, a sensing element may refer to any element or unit that can be used to read out a sensor signal that allows the respective physical observable to be measured or quantified. The sensing elements may comprise, for example, one or more of capacitive, inductive, and / or resistive sensing elements, such as microelectrodes, thermistors, or microelectromechanical systems (MEMS), piezoelectric sensing elements, Hall effect sensing elements, and light-sensitive sensing elements, such as photodiodes, and the sensor signal may be, for example, a current or a voltage. In some embodiments, some or all of the sensing elements may be atomic-scale or molecular-scale sensing elements, e.g., atomic-scale or molecular-scale structures with optical absorption and / or emission spectra that depend on the physical observable, and the sensor signal may be, for example, a transmitted light intensity or an emitted light intensity. The sensing elements may in particular be solid-state spin systems, e.g., as described in more detail below.

[0012] The physical observable may be any measurable physical quantity, for example, temperature, pH value, electrical conductivity, dielectric constant, electric field, magnetic field, and / or light intensity. Each of the sensing elements may be configured to measure the same physical observable, or at least some of the sensing elements may be configured to measure different physical observables. In some examples, the sensing elements may be configured to measure, for example, a first physical observable at the position of the respective sensing element, which may depend on a second physical observable, for example, the same or a different physical observable at different positions around the sensing element or in a sensing volume, in particular in a measurement volume or in a sensing volume. Thus, the sensor signal of the sensing element may characterize the second physical observable in addition to the first physical observable.

[0013] The sensing elements may be distributed homogeneously throughout the sensing layer, e.g., with a uniform density and / or uniform spacing between adjacent sensing elements, or may be confined to spatially separated regions within the sensing layer, e.g., as described in more detail below. A collection of adjacent sensing elements within a region or portion of the sensing layer may be referred to as a sensing region hereinafter. The sensing elements within a given sensing region may be spatially separated from other sensing elements in the sensing layer, or may be a subset of sensing elements selected from sensing elements distributed throughout the sensing layer, e.g., sensing elements within a selected region or portion of the sensing layer that may not be spatially separated from other sensing elements in the sensing layer.

[0014] In some embodiments, the sensing elements may form a plurality of sensors. Each of the sensors may comprise one or more sensing elements, e.g., a collection of sensing elements configured to generate a common sensor signal, which may be, for example, a sum or average of the sensor signals of the sensing elements in the collection. The sensors may be spatially separated and / or configured to be read out independently of the other sensors. In some embodiments, each of the sensors may comprise a sensing element in a respective sensing region, which may be spatially separated from each other, i.e., each sensor may correspond to one of a plurality of spatially separated sensing regions in the sensing layer. In some examples, some or all of the sensors may comprise only a single sensing element.

[0015] In some embodiments, performing measurements on one or more samples may include selecting a subset of sensing elements for each of the one or more samples and selectively determining a sensor signal from the sensing elements in the respective subset. For example, the sensor signal may be determined only for the sensing elements in the subset associated with the one or more samples for which the measurements are performed. The sensing elements in the subset for a given sample may be, for example, located within a sensing region, in particular within a sensing region adjacent to the respective sample object in the self-assembled structure. The subset may, for example, comprise all sensing elements within the respective sensing region. For sensing elements outside the sensing region associated with the one or more samples for which the measurements are performed, i.e. sensing elements in other parts of the sensing layer, the sensor signal may not be determined.

[0016] Selecting a subset of the sensing elements and selectively determining sensor signals from sensing elements in the subset, e.g., in the respective sensing regions, may include selectively activating the sensing elements in the subset and / or selectively reading out the sensing elements in the subset. For example, only sensing elements in sensing regions associated with one or more samples for which measurements are performed may be activated and / or read out. Activating the sensing elements may include, for example, changing a state of the sensing elements, e.g., from an off state in which the sensing elements do not generate a sensor signal, to an on state in which the sensing elements generate a sensor signal. The sensing elements may be activated, for example, electrically, e.g., using an electrical switch, and / or optically, e.g., by optically exciting the sensing elements. Selectively reading out the sensing elements in the subset may include, for example, measuring sensor signals only for sensing elements in the respective subset, or discarding sensor signals for sensing elements not included in the respective subset, e.g., when processing or analyzing the measured sensor signals.

[0017] In some embodiments, the sensing elements in the sensing layer form an array of spatially separated sensors, each of the sensors comprising one or more sensing elements. In the self-assembled structure, each sample object may be disposed adjacent to each of the sensors in the array, and measurements on the sample may be performed using each sensor. In some examples, the sensors in the array may be spatially separated sensing regions, each of which comprises multiple sensing elements.

[0018] The sensors can be arranged in a one-dimensional array, where the sensors may be arranged along a first direction, e.g., with a space between adjacent sensors, or in a two-dimensional array, where the sensors may be arranged in a plane, e.g., with a space between adjacent sensors. In some embodiments, the sensor array can be a periodic array. The sensors may be arranged in a one-dimensional periodic array, where the sensors may be positioned, e.g., at equidistant intervals along the first direction. Preferably, the sensors are arranged in a two-dimensional periodic array, where the sensors may be positioned, e.g., at a first equidistant interval in the first direction and at a second equidistant interval in the second direction. The second interval may be the same as or different from the first interval. Preferably, all sensors of the array are arranged in a common plane, which may be parallel to a wall of the measurement volume. The sensing elements may be embedded, e.g., in a bottom or top wall of the measurement volume, and a surface of each sensing element may be exposed to the measurement volume. In other examples, the sensing elements may be fully embedded in the bottom or top wall, such that the sensing elements are not exposed to the measurement volume. Each sensor may be associated with a respective unit cell of the array, which is the basic unit from which the array is formed by successive tiling or translation of identical unit cells. A unit cell of an array may, for example, be an area that is closer to a given sensor than any other sensor of the array.

[0019] In a preferred embodiment, the physical dimensions of each sample object correspond to the spacing of the sensor array, i.e. the pitch or center-to-center distance between adjacent sensors in the sensor array along the first and / or second direction. The sample objects may be, for example, monodisperse objects having a diameter or width corresponding to the first and / or second spacing of the sensor array. To this end, the spacing of the sensor array may be selected such that when probing sample objects of a given size, such as, for example, cells or beads, the spacing of the sensor array corresponds to the physical dimensions of the sample objects. In other words, the sensor chip provided may be adapted to the physical dimensions of the sample objects. Alternatively, the physical dimensions of the sample objects may be selected such that when probing sample objects having an adjustable size, such as, for example, microdroplets, the physical dimensions of the sample objects correspond to the spacing of the sensor array. For example, the flow rate of the carrier fluid and / or the sample fluid in the droplet generator, the viscosity of the carrier fluid and / or the sample fluid, and / or the surface tension at the carrier fluid-sample fluid interface may be adjusted to adapt the physical dimensions of the microdroplets to the spacing of the sensor array. In some embodiments, the physical dimensions of the sample object may be larger than the physical dimensions of the sensor or sensing region, for example, the diameter or width of the sample object may be at least 50% larger, and in some cases at least 100% larger, than the diameter or width of the sensor or sensing region.

[0020] The sample objects may be, for example, microdroplets dispersed in a carrier fluid. The microdroplets may, for example, comprise or consist of a sample fluid, which may be, for example, a biological sample fluid, which may contain biological samples such as proteins, DNA, bacteria, cells or parts thereof, or a chemical sample fluid, which may contain, for example, one or more reagents and / or products of a chemical reaction. The microdroplets may have a well-defined shape (e.g., spherical) in the carrier fluid, for example, due to surface tension at the interface between the microdroplets and the carrier fluid, which may also prevent the microdroplets from fusing when they come into contact with each other. In some examples, the microdroplets may be monodisperse microdroplets, i.e., have the same diameter or width. In other embodiments, the sample objects may also be other objects, in particular cells or components thereof, solid particles, or microbubbles. The sample objects may, for example, be microbeads, for example agarose beads, or magnetic particles.

[0021] In some examples, the sample fluid and the carrier fluid may be immiscible, the sample fluid may be, for example, an aqueous solution, and the carrier fluid may include a hydrophobic fluid, for example, an oil. Preferably, the carrier fluid includes one or more of toluene, chloroform, methanol, dimethylsulfoxide (DMSO), and tetrahydrofuran (THF). The carrier fluid and the microdroplets may form an emulsion in which the carrier fluid is the continuous phase and the sample fluid is the dispersed phase. Additionally or alternatively, the carrier fluid and / or the sample object may include a surfactant, such as an amphiphilic molecule, for example, to stabilize the microdroplets in the carrier fluid. The microdroplets may include, for example, a shell layer formed by a surfactant, which may surround, for example, a core containing the sample fluid. In some examples, the microdroplets are vesicles or liposomes having a lipid bilayer surrounding a core formed by the sample fluid.

[0022] A carrier fluid containing a plurality of sample objects is provided to the measurement volume, for example by pipetting into the measurement volume or through an inlet channel of the sensor chip. The number of sample objects in the measurement volume is controlled so that the sample objects form a self-assembled structure in the measurement volume. To this end, the number of sample objects in the measurement may be adjusted, for example by providing additional sample objects to the measurement volume or by removing sample objects from the measurement volume. This may include, for example, continuously providing carrier fluid containing sample objects to increase the number of sample objects in the measurement volume until a self-assembled structure is formed. In some embodiments, this may also include expelling the carrier fluid from the measurement volume without removing the sample objects therefrom, for example by pipetting or through an outlet channel having a cross-sectional area smaller than the cross-sectional area of ​​the sample objects.

[0023] In the context of the present disclosure, a self-assembled structure of sample objects refers to a structure in which the arrangement of the sample objects is at least partially determined by interactions between the sample objects themselves, for example, by repulsive and / or attractive surface-surface interactions between sample objects that are in contact with or in close proximity to each other. In some embodiments, the interactions between the sample objects may be at least partially mediated by a carrier fluid. Interactions with adjacent sample objects may prevent movement of a given sample object within the self-assembled structure. In other words, the position of a given sample object in the self-assembled structure may not be determined by, or at least not solely by, structural features of the sensor chip. In some embodiments, the self-assembled structure may be periodic, for example, such that adjacent sample objects are positioned at equidistant intervals in one or two directions.

[0024] In the self-assembled structure formed in the measurement volume, the sample objects may be arranged, for example, such that each sample object is adjacent to each of the sensors in the sensor array. For example, the sample objects may be aligned with the unit cells associated with the respective sensors. In some examples, the center of the sample object may be aligned with the center of the respective sensor, for example, such that the distance between the center of the sample object and the center of the respective sensor is minimized. In some examples, the sample object may be in contact with the surface of the respective sensor or with the surface of the wall portion of the measurement volume closest to the respective sensor. Preferably, each of the sample objects is arranged adjacent to the respective sensor. The self-assembled structure may have, for example, the same structure as the sensor array, i.e., the sample objects may be arranged in the same pattern as the sensors. In some embodiments, the self-assembled structure may be periodic and have the same lattice structure as the sensor array, i.e., the sample objects may be arranged in the same periodic pattern as the sensors, for example, such that each of the sample objects is aligned with a respective one of the unit cells of the array.

[0025] In other embodiments, the sample objects in the self-assembled structure may be arranged such that a part or all of the sample objects are located adjacent to a respective sensing area in the sensing layer, each sensing area may comprise sensing elements of a subset of sensing elements selected for the respective sample. In other words, the arrangement of the sample objects in the self-assembled structure may be adapted to the arrangement of the selected subset or sensing area in the sensing layer, or vice versa. In some examples, the sensing area may be a predetermined sensing area that may be defined by structural features of the sensor chip, such as the distribution of sensing elements in the sensing layer, or may be selected before the formation of the self-assembled structure, and the sample objects in the self-assembled structure may be arranged such that a part or all of the sample objects are located adjacent to the respective predetermined sensing area.

[0026] After the self-assembled structure is formed, measurements are performed using some or all of the sensing elements in the sensing layer while the sample object is placed in the self-assembled structure. Measurements on the samples may be performed, for example, using sensing elements of a sensing area or sensor associated with the respective sample. Preferably, the sample object does not move while the measurements are performed, i.e. the self-assembled structure may be stationary during the measurements. In some cases this may include interrupting the flow of carrier fluid through the measurement volume.

[0027] By preparing the self-assembled structures in the measurement volume, the sample objects can be positioned adjacent to the corresponding sensing areas or sensors without the need for individual structural features, such as hydrophilic or hydrophobic surface coatings for each of the sample wells or sensing areas or sensors. Instead, a small number of boundaries or guiding structures, such as side walls of the measurement volume, can be used to globally define the position of the self-assembled structures relative to the sensing areas or sensor array. This allows, for example, to use measurement volumes with flat walls, which greatly facilitates the manufacture of the sensor chip and its handling. In particular, the measurement volume can be cleaned more easily than individual sample wells, which may allow the sensor chip to be reused multiple times without risk of contamination. This not only reduces costs but also increases throughput, since the sensor chip does not need to be replaced between measurements. Furthermore, the positioning of individual sample objects, for example by targeted pipetting, is not required, simplifying the preparation of the samples on the sensor chip. The proposed method can therefore be easily automated, enabling fast and cost-effective parallel probing of a large number of samples.

[0028] Microdroplets arranged in periodic structures have been used previously to increase the density of microdroplets used as microreactors, for example, in the image plane of a microscope, see US 2012 / 0184464 and ACHatch et al, Lab Chip, 2011, 11, 2509. Similar methods for forming microdroplet arrays in microfluidic structures are known, for example, in CE Stanley et al., Chem. Commun., 2010, 46, 1620-1622 and P. Parthiban et al., Soft Matter, 2019, 15, 4244-4254.

[0029] The sensor chip may comprise boundary or guiding structures configured to limit or guide the movement of the sample object in the measurement volume. The boundary or guiding structures, hereinafter collectively referred to as boundary structures, may comprise, for example, one or more of the following: a side wall of the measurement volume, a guiding wall protruding from the bottom wall and / or top wall of the measurement volume, and / or a hydrophilic and / or hydrophobic coating on the bottom wall and / or top wall of the measurement volume, as will be described in more detail below. The self-assembled structure may be formed by interaction between the sample object and the boundary structures and by surface-surface interactions between the sample objects. The interaction between the sample object and the boundary structures may, for example, be a direct interaction of the boundary structures with the sample object itself or may be mediated by a carrier fluid. The boundary structures may, for example, be arranged or shaped such that the self-assembled structures are aligned with respect to the sensing area or the sensor array, as will be described below with respect to the sensor chip according to the invention and the sensing device according to the invention. For this purpose, the boundary structures may, for example, be arranged at a distance corresponding to half the spacing of the sensor array from the outermost sensor in the array. The boundary structures may, for example, be aligned with the edges of the unit cells of the sensor array, such that, for example, an edge of each of the outermost unit cells of the sensor array is aligned with one of the boundary structures.

[0030] In the self-assembled structure, the interaction between the sample object and the boundary structure and the surface-surface interaction between the sample objects can prevent the sample object from moving and thus fix the sample object in a predetermined position, which may be, for example, adjacent to the respective sensor or sensing area. In other words, for example, since the respective sample objects are in contact, it may not be possible to move a given sample object without moving at least one other sample object. Preferably, the self-assembled structure is formed such that at least 90%, and in some cases at least 95%, of the sample objects are prevented from moving along two or more orthogonal directions, for example in a plane parallel to the bottom or top wall of the measurement volume. This may be sufficient to prevent the entire self-assembled structure from moving or collapsing during the measurement. In some cases, the sample object in the self-assembled structure arranged adjacent to the entrance or exit of the measurement volume may still be able to move in one or more directions without moving other sample objects.

[0031] In some embodiments, the sample object may have a circular cross section. The sample object may have, for example, a spherical, spheroidal, elliptical, or cylindrical shape. The self-assembled structure may be, for example, a close packing of circles when projected or observed along a direction perpendicular to the sensing layer and / or the wall of the measurement chamber adjacent to the sensing layer. In close packing of circles, the sample objects may be arranged in a single layer such that their circumferences are in contact or close to each other, thus preventing the sample objects from moving. Close packing of circles may correspond to the closest possible arrangement of the sample objects under boundary conditions imposed by the boundary structures in the measurement volume.

[0032] In some embodiments, the sample objects in the self-assembled structure may not have a circular cross-section, but the self-assembled structure may nevertheless resemble a close packing of circles, e.g., in the sense that the centers of the sample objects and / or the contact points between the sample objects are aligned with corresponding points in an ideal close packing of circles. The circumference of the sample objects in the self-assembled structure may be tangent to a circle in the close packing of circles (or vice versa), e.g., at the points where the sample objects are in contact or close to adjacent sample objects. The physical dimensions of the sample objects may, e.g., be equal to the diameter of the close packing circle. The sample objects may have an essentially non-circular cross-section, e.g., when provided in the carrier fluid, and / or may deform when forming the self-assembled structure, e.g., when contacting adjacent sample objects and / or boundary structures of the sensor chip.

[0033] The self-assembled structure may in particular be a close packing of equal circles, i.e., a close packing of circles having the same diameter. All of the sample objects may, for example, have a circular cross section with the same diameter. Thus, some or all of the sample objects may, for example, be arranged in a two-dimensional hexagonal lattice in the self-assembled structure, i.e., each sample object is surrounded by six equidistant neighboring sample objects, thereby forming a self-assembled periodic structure. The two-dimensional hexagonal lattice corresponds to a close packing of equal circles in a uniform space, which may hereinafter also be referred to as a uniform close packing of equal circles. In another example, some or all of the sample objects may be arranged in a linear chain in the self-assembled structure, each sample object being in contact with two neighboring sample objects.

[0034] In some cases, the sample objects may have a spherical shape and the self-assembled structure may be a close packing of spheres, in particular a close packing of equal spheres, i.e. may correspond to the densest possible arrangement of spheres under boundary conditions imposed by the boundary structure in the measurement volume. The sample objects in the self-assembled structure may be arranged in a single layer, for example in a single plane, and the close packing of spheres in a single layer corresponds to the close packing of circles when projected in a direction perpendicular to the layer.

[0035] In some embodiments, the carrier fluid containing the sample objects can be provided through a microfluidic inlet channel in fluid communication with the measurement volume. Controlling the number of sample objects in the measurement volume can include maintaining a flow of the carrier fluid containing the sample objects through the inlet channel until a self-assembled structure is formed. In this way, sample objects can be added to the measurement volume continuously until a self-assembled structure is formed. In some examples, this can include releasing the carrier fluid from the measurement volume, for example through a microfluidic outlet channel, while preventing the sample objects from leaving the measurement volume, for example by using an outlet channel with a width or cross-sectional area smaller than the width and cross-sectional area of ​​the sample objects, respectively, or by appropriately adjusting the width or cross-sectional area of ​​the outlet channel, for example using a valve.

[0036] In a preferred embodiment, the method further comprises tracking the movement of one or more sample objects on the sensor chip, e.g., before and / or after performing measurements on the respective samples. Tracking the movement of the sample object may, for example, include determining when the sample object reaches one or more predefined points on the sensor chip, e.g., an entrance of a measurement volume, an exit of a measurement volume, and / or an output port of the sensor chip. Tracking the movement of the sample object may further include associating the sample object with a respective sensor or sensing element, e.g., to associate the sample object with a measurement result obtained from the respective sensor or sensing element. Additionally or alternatively, tracking the movement of the sample object may also include associating the sample object and / or the measurement result with information regarding the composition and / or formation process of the sample object. The sample object may, for example, be formed with a composition and / or other properties that change over time, e.g., using a droplet generator. Tracking the movement of the sample objects may allow the sample objects and / or the measurement results to be associated with the time at which the respective sample objects were formed, a particular composition, e.g., the concentration of the sample substance, and / or a particular parameter used to form the sample objects, e.g., the flow rate in the droplet generator, the fluid composition, and / or the temperature. The movement of the sample objects may be tracked, for example, based on the flow rate of the carrier fluid, the duration of the flow of the carrier fluid, and / or the position of the respective sensor or sensing element. In a preferred embodiment, the movement of one or more sample objects on the sensor chip is tracked continuously, for example, by determining the position of the sample objects on the sensor chip at multiple time points. The one or more sample objects may be tracked, for example, using a camera configured to record images of the sample objects on the sensor chip. Tracking the sample objects on the sensor chip may allow, for example, to sort the sample objects based on the respective measurement results. In some examples, the sample objects may include markers that allow the sample objects to be distinguished from one another, for example, by spectroscopic means, as described, for example, in Y.Feng et al., Microsystems&Nanoengineering Vol.6,109(2020).

[0037] In a preferred embodiment, the sensing element is a magnetic quantity sensing element, for example an atomic or molecular scale structure exhibiting a magnetic field dependent behavior, for example a magnetic field dependent energy spectrum and / or a magnetic field dependent transition rate between different states of the magnetic quantity sensing element. The sensing element may in particular be an optically addressable solid-state spin system. An optically addressable solid-state spin system is a quantum system with a spin degree of freedom arranged or embedded in a solid host material, which can be read out and / or manipulated via optical transitions and / or microwave fields. The spin system may in particular be an object that behaves like an artificial atom or molecule, i.e. a system that exhibits an atom- or molecule-like energy spectrum and has at least two different spin states. The spin system may for example be an optically active defect in a crystal structure. The energy levels of the different spin states may shift in the presence of a magnetic field. Furthermore, the spin system may for example have a spin state dependent transition rate between different states of the spin system (for example electronic states of the spin system). Thus, the solid-state spin system may be used as a probe for magnetic fields, for example by determining the energy difference and / or transition rate between the states of the spin system. In a preferred embodiment, the substrate comprises or consists of diamond and the solid-state spin system is a diamond color center, i.e. an optically active point defect in the diamond crystal structure. Preferably, the spin system is a nitrogen vacancy (NV) center in diamond, in particular a negatively charged nitrogen vacancy center.

[0038] Performing a measurement on the sample may include illuminating light onto a solid-state spin system disposed in a sensing region adjacent to each sample object in the self-assembled structure to optically excite the solid-state spin system in the sensing region, and detecting an optical signal emitted by the solid-state spin system in the sensing region.

[0039] Preferably, the solid-state spin systems in some or all of the sensing regions are excited simultaneously by illuminating the sensing regions with light propagating along an optical illumination path through the sensor chip connecting some or all of the sensing regions, i.e., such that a light pulse propagating along the illumination path passes through each sensing region sequentially. The wavelength of the light can, for example, be tuned to the absorption wavelength of the spin systems. Illumination of the sensing regions along the illumination path can be used, inter alia, to optically polarize the spin systems in the sensing regions and / or to excite the spin systems in the sensing regions to induce an optical signal that is detected, i.e., for optical readout. The intensity and / or pulse duration of the light pulses may, for example, be selected such that the spin systems are prepared in a predefined quantum state. In some cases, the intensity and / or pulse duration may be selected such that the spin systems in the sensor undergo multiple transitions, for example, to increase the fluorescence intensity and / or for optical polarization of the spin systems, i.e., to optically pump the spin systems to a predefined state. In a preferred embodiment, the sensing regions are illuminated multiple times, for example, a first time for optical polarization and a second time for inducing an optical signal that is detected. At least one of the illuminations, and preferably both, is produced by light propagating along an illumination path.

[0040] The optical signals can be detected simultaneously, for example using a multi-channel photodetector. The optical signals can be, for example, the intensity of light emitted by the spin system at one or more emission wavelengths (e.g., fluorescence emitted by an excited spin system) or the intensity of light transmitted through the sensing region, for example to determine the absorption rate of light at one or more absorption wavelengths by the spin system. The detected signals can, for example, make it possible to extract information about the state of the spin system, for example the occupation probability of one or more spin states, which can be used, for example, to extract information about the strength and / or orientation of the magnetic field at each sensor, which may arise at least in part from the corresponding sample.

[0041] The present invention further provides a sensor chip for parallel probing of multiple samples using a method according to any one of the embodiments described herein. The sensor chip comprises a measurement volume configured to receive a carrier fluid containing multiple sample objects. The sensor chip further comprises an array of sensors arranged in or adjacent to a first wall of the measurement volume, the sensor array having a first spacing a1. Each of the sensors comprises one or more sensing elements, each of which is configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element. The sensor chip comprises two or more boundary or guiding structures configured to restrict or guide the movement of the sample objects in the measurement volume. The two or more boundary or guiding structures are arranged such that a close-packing of solid objects having a circular cross-section with a diameter equal to the first spacing a1 is arranged in the measurement volume, and when the close-packing of the solid objects covers the entire first wall of the measurement volume, the two or more boundary or guiding structures confine the solid objects such that each solid object is aligned with each of the sensors.

[0042] The sensor chip may comprise a single-layer or multi-layer substrate, and preferably the substrate or at least a part thereof is optically transparent in the ultraviolet, visible, and / or near-infrared spectrum. The measurement volume may be, for example, a recess in the top surface of the substrate, or a hollow volume surrounded by the substrate. In some embodiments, the sensor chip may comprise a removable cover for opening and closing the measurement volume. In addition, the sensor chip may comprise a microfluidic structure, such as an inlet channel and / or an outlet channel, in fluid communication with the measurement volume to provide or discharge the carrier fluid to / from the measurement volume. The sensor chip may also comprise a droplet generator, for example as described in more detail below. The first wall may be, for example, a bottom wall or a top wall of the measurement volume, which may be formed, for example, by the substrate and / or the removable cover. Preferably, the first wall has a flat surface and does not comprise any protrusions and / or depressions. In some examples, the surface of the sensor and / or the surface of the sensing element may be exposed to the measurement volume, for example, flush with the surface of the first wall. In other examples, the sensors and / or sensing elements may be fully embedded within the first wall or within another layer below the first wall and may not be exposed to the measurement volume. In some embodiments, each of the sensors may comprise a sensing element within a respective sensing region, e.g., as detailed above. The sensing elements may be confined to a plurality of spatially separated sensing regions, e.g., within the first wall or within a sensing layer adjacent thereto, and the sensing regions are arranged in an array, thereby forming an array of sensors.

[0043] The sensors may be arranged in a one-dimensional array or a two-dimensional array. The sensors may be arranged in a one-dimensional periodic array, where the sensors may be positioned, for example, at equidistant intervals a1 along a first direction. Alternatively, the sensors may be arranged in a two-dimensional periodic array, where the sensors may be positioned, for example, at a first equidistant interval a1 in a first direction and at a second equidistant interval a2 in a second direction. In the following, the first interval or the second interval may also be referred to as the interval a0 of the sensor array. Any reference to the interval a0 should therefore be understood as referring to the first interval for a one-dimensional array and to either the first interval a1 or the second interval a2 for a two-dimensional array.

[0044] Preferably, all of the sensors are arranged in the same plane, which may be, for example, parallel to the first wall. The sensors may be arranged, for example, in a substrate of the sensor chip adjacent to the measurement volume or in a sensing layer on the substrate. Each sensor may be associated with a respective unit cell of the array, the unit cell being the basic unit of which the array is formed by successive tiling or translation of identical unit cells. In one example, the sensors are arranged in a two-dimensional hexagonal lattice, i.e., such that each sensor is surrounded by six equidistant neighboring sensors. Thus, the unit cell of the array may be, for example, hexagonal, with the edge of the unit cell associated with a given sensor being defined by the perpendicular bisector of the vector connecting the sensor to its neighboring sensors. In another example, the sensors are arranged in a two-dimensional rectangular lattice, with the unit cell of the array having a rectangular shape. In yet another example, the sensors are arranged in a one-dimensional equidistant chain, with the unit cell being defined, for example, as a square around a given sensor, with the size of the square corresponding to the spacing a0 between adjacent sensors.

[0045] The boundary or guiding structure, hereinafter collectively referred to as boundary structure, may for example comprise one or more side walls of the measurement volume, each of which extends at an angle to the first wall, preferably at an angle of more than 60°. The side walls may in particular be perpendicular to the first wall. Preferably, some or all of the side walls of the measurement volume have a flat surface, i.e. do not comprise any inclined portions, protrusions and / or depressions. Additionally or alternatively, the boundary structure may comprise one or more guiding walls protruding from the first wall of the measurement volume and / or from a second wall of the measurement volume facing the first wall. The boundary structure may further comprise one or more hydrophilic and / or hydrophobic coatings on the first and / or second walls of the measurement volume, the coatings for example defining areas on the first wall that can be wetted by the carrier fluid or areas of the first wall that cannot be wetted by the carrier fluid.

[0046] The boundary structure is arranged such that when a sufficiently large number of solid objects having a circular cross section that cannot be deformed and has a diameter equal to the spacing a0 of the sensor array are arranged on the first wall, the solid objects are arranged in a planar close packing in which each solid object is aligned with each of the sensors. The solid objects may have, for example, a spherical, spheroidal, elliptical or cylindrical shape. When projected along a direction perpendicular to the first wall, the close packing of the solid objects can correspond to the close packing of equal circles. Each solid object can be arranged above each of the sensors, for example, such that the center of the solid object in a plane parallel to the first wall is aligned with the center of the sensor and / or such that the solid object is arranged within a unit cell associated with the sensor, for example such that an edge of the unit cell is tangent to the circumference of the solid object when viewed along a direction perpendicular to the first wall. As detailed above, the close packing of the solid objects having a circular cross section can correspond to the densest possible arrangement of the solid objects under the boundary conditions imposed by the boundary structure in the measurement volume. In the resulting structure, each of the solid objects may be in contact with at least one other solid object. Furthermore, at least a portion of the solid object may be in contact with one or more of the bounding structures. Contact between the solid object and the bounding structures may destroy the inherent translational invariance of the uniform close packing of equal circles, thereby fixing the solid object in a desired arrangement. In some embodiments, one or more of the bounding structures may confine the solid object by an interaction mediated by the carrier fluid, instead of or in addition to a direct interaction with the solid object. For example, a hydrophilic or hydrophobic coating may promote or prevent wetting of the respective surfaces by the carrier fluid, thereby confining the object provided in the carrier fluid. In other words, in some examples, the close packing of the solid objects in the measurement volume is formed and / or aligned with the sensor array only when the solid objects are provided in the carrier fluid.

[0047] Thus, the two or more boundary structures may be configured to confine a plurality of sample objects having a circular cross section, which are not truly non-deformable solid objects as described above, to a self-organized close packing of equal circles in the measurement volume, such that each sample object is located adjacent to each of the sensors. In other words, when a sufficiently large number of sample objects are located in the measurement volume, the sample objects form a self-organized structure in the measurement volume in which each sample object is aligned with each of the sensors in the sensor array. As detailed above with respect to the method according to the invention, the same applies to sample objects that do not have a circular cross section, but are nevertheless configured to form a self-organized structure that resembles a close packing of equal circles. The physical dimensions of the sample objects may, for example, be selected such that the physical dimensions of the sample objects correspond to the spacing of the sensor array.

[0048] As detailed above, the sensor array can correspond to a tiling of identical unit cells, with each sensor associated with a respective unit cell. The boundary structures can, for example, be arranged such that segments of the boundary structures are aligned with edges of the unit cells of the sensor array along the circumference of the sensor array to confine the sample objects to their respective unit cells within the self-assembled structure, for example, by interactions between the sample objects and the boundary structures and between the sample objects themselves. Preferably, the edges of each of the outermost unit cells of the sensor array are aligned with one of the boundary structures.

[0049] In some embodiments, each of the outermost sensors in the sensor array may be positioned at a distance corresponding to half the first spacing a1, i.e., a1 / 2, from at least one of the boundary structures, and the distance between the sensor and the boundary structure may be, for example, the distance between the center of the sensor and the respective boundary structure. In this way, a sample object having a physical dimension corresponding to the first spacing, e.g., a diameter corresponding to the first spacing, aligned with one of the outermost sensors may be in contact with the respective boundary structure. The outermost sensor of the sensor array may be, for example, a sensor that allows each solid object in the close packing aligned with the sensor to be moved without moving another solid object if it is not completely confined by other solid objects in the close packing, i.e., not a boundary structure.

[0050] In some embodiments, the two or more boundary structures are positioned such that in close packing of the solid objects, each solid object aligned with each of the sensors, e.g., aligned with a respective unit cell, contact between the solid objects and between the solid objects and the boundary structures prevents at least 90%, preferably at least 95%, of the solid objects from moving in a plane parallel to the first wall.

[0051] In some embodiments, the two or more boundary structures comprise two opposing boundary structures separated by a distance D equal to an integer multiple of the spacing a0 of the sensor array, i.e. D=M·a0, where M is a positive integer, in particular an integer greater than 1. The integer M may be, for example, between 5 and 1000, in one example between 10 and 100. This may enable, for example, M solid or sample objects having a physical dimension corresponding to a0, for example a diameter corresponding to a0, to be positioned between the opposing boundary structures such that the M solid or sample objects are in contact with each other and with the opposing boundary structures, thereby forming a substantially incompressible chain (e.g. a chain that can only be deformed by deforming the solid or sample object).

[0052] Additionally or alternatively, the two or more boundary structures may be spaced apart by a distance a0 of the sensor array.

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[0053] As described above, the sensor array can be a two-dimensional periodic array having a first spacing a1 in a first direction and a second spacing a2 in a second direction. The second spacing a2 can be equal to or different from the first spacing a1. In some examples, the sensors in the array can be arranged in, for example, a rectangular grid, where the second direction is perpendicular to the first direction and the second spacing is different from the first spacing.

[0054] In a preferred embodiment, the sensors in the array are spaced apart by a h The hexagonal lattice is arranged with two basis vectors or transformation vectors, which correspond to the two sides of an equilateral triangle.

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[0055] In some embodiments, the sensor chip may further comprise a droplet generator configured to generate microdroplets of the sample fluid in the carrier fluid, in particular monodisperse microdroplets, i.e. microdroplets having a uniform size. The droplet generator may be configured to generate the microdroplets, for example, by cross-flow droplet generation, e.g., a T-junction, where a first flow path, through which the carrier fluid is provided, crosses at an angle with a second flow path, through which the sample fluid is provided. In other examples, the droplet generator may be configured to generate the microdroplets by parallel flow droplet generation, by hydrodynamic flow focusing, and / or by step emulsification. The size of the microdroplets may be controlled, for example, by adjusting the flow rate and / or composition of the carrier fluid and / or the sample fluid.

[0056] In some embodiments, the sensor chip may comprise a microfluidic inlet channel and a microfluidic outlet channel, the inlet and outlet channels being in fluid communication with the measurement volume. The sensor chip may further comprise means for selectively preventing the sample object from leaving the measurement volume through the outlet channel. The sensor chip may comprise, for example, a valve configured to adjust a width or a cross-sectional area of ​​a portion of the outlet channel, such that, for example, the carrier fluid can be released from the measurement volume through the outlet channel, but the sample object cannot pass through the valve.

[0057] Each of the sensing elements is configured to generate a sensor signal, in particular an optical, magnetic and / or electrical sensor signal, which characterizes a physical observable in the vicinity of the respective sensing element, for example at the position of the respective sensing element or in a sensing volume around the respective sensing element, for example as detailed above with respect to the method according to the invention. The sensor signal may characterize, for example, a temperature, a pH value, an electrical conductivity, a dielectric constant, an electric field, a magnetic field and / or a light intensity. Each of the sensing elements may, for example, comprise one or more of an electrode, in particular an electrode exposed to the measurement volume, a capacitive sensing element, an inductive sensing element, a resistive sensing element, a piezoelectric sensing element, a Hall effect sensing element and a photodiode.

[0058] In a preferred embodiment, the sensor is a magnetic quantity sensor and the sensing element is a magnetic quantity sensing element, each of the sensors comprising a plurality of magnetic quantity sensing elements. The sensing element may be, for example, an optically addressable solid-state spin system, for example as detailed above. The optically addressable solid-state spin system may in particular be a nitrogen vacancy (NV) center in diamond. The NV center can be used, for example, to measure electric and magnetic fields locally (see, for example, R. Schirhagl et al., Annu. Rev. Phys. Chem. 65, 83-105 (2014)) and to perform nuclear magnetic resonance (NMR) spectroscopy on small samples, as reported, for example, in DRGlenn et al., Nature 555, 351-354 (2018) and WO2018 / 052497A2.

[0059] The solid-state spin system may be disposed in a sensing region, for example located in a sensing layer, which may be, for example, a surface layer below the surface of the first wall exposed to the measurement volume. The sensing layer may, for example, comprise or consist of diamond and may have a thickness perpendicular to the surface of 1 μm to 1000 μm, in some examples 2 μm to 100 μm, in one example 5 μm to 10 μm. In some examples, the sensing layer may at least partially form the top surface of the first wall. In other examples, one or more additional layers, for example optical coatings, may be disposed between the sensing layer and the surface of the first wall. In some examples, the spin system may be confined to the sensing region, while in other examples, the spin system may be distributed throughout the surface layer. In some embodiments, the density of the spin systems in the sensing layer outside the sensing region may be at least 100 times lower, preferably at least 1000 times lower, than the density of the spin systems in the sensing region.

[0060] In some embodiments, the sensor chip may comprise a light guiding system configured to provide an optical path through the sensor chip, the optical path connecting some or all of the sensing areas such that light propagating along the optical path passes through each sensing area in sequence at least once. In other words, some or all of the sensing areas may be arranged along an optical path provided by the light guiding system. Preferably, light propagating along the optical path passes through each sensing area the same number of times, e.g. once.

[0061] The light guiding system may comprise one or more optical elements that modify the propagation of light along the light path, such as, in particular, a reflective structure, an optical coating, and / or a waveguide. The light guiding system may comprise, for example, one or more reflective coatings, in particular, a broadband or dichroic reflective coating. The reflective coating may be arranged, for example, on the surface of the first wall exposed to the measurement volume, on the bottom surface of the substrate opposite the surface of the first wall, and / or on one or more side surfaces of the substrate extending between the top and bottom surfaces. In some cases, the propagation of light along the light path may also include one or more total internal reflections at the surface of the sensor chip, i.e. the light guiding system may be configured such that the angle of incidence of the light path on the respective surface is greater than the critical angle for total internal reflection.

[0062] In some embodiments, at least two segments of the light path are not parallel to each other, for example due to reflections from reflective elements of the light guiding system or due to curvatures or bends of the waveguiding elements of the light guiding system. Each of the non-parallel segments may in particular be located or extend between two or more of the sensing regions. In some cases, the light path may additionally comprise one or more sets of parallel segments. The light path may form a periodic pattern, for example a zigzag pattern and / or a meandering pattern, for example in one or more planes, for example perpendicular or parallel to the surface of the first wall. In some cases, the light path may form a non-intersecting pattern, in particular a non-intersecting periodic pattern.

[0063] The sensors and / or sensing elements may be exposed to the measurement volume or may be separated from the measurement volume by a portion of the first wall. The sensors and / or sensing elements may, for example, be completely embedded in the first wall or may be arranged in a layer below the first wall. The distance between each of the sensors and the surface of the first wall exposed to the measurement volume may, for example, be less than 5 times, preferably less than 2 times, the spacing a0 of the sensor array. In some examples, the distance between the sensors and the surface of the first wall may be equal to or less than the spacing a0, and in one example may be less than 50% of the spacing a0. This may facilitate interaction between the respective sensing elements and the sample object in the measurement volume and may reduce crosstalk between the sensors. The distance between the sensors and the surface of the first wall may, for example, be the distance between the center of the sensor and the surface of the first wall.

[0064] The present invention further provides a sensing device for parallel probing of multiple samples using a method according to any one of the embodiments described herein. The sensing device comprises a sensor chip, the sensor chip comprising a substrate and a measurement volume configured to receive a carrier fluid containing multiple sample objects. The substrate comprises a plurality of optically addressable sensing elements arranged in a sensing layer in or under a first wall of the measurement volume, each of the sensing elements configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element. The sensing device further comprises an illumination system for illuminating the sensing elements. The sensor chip comprises two or more boundary or guiding structures configured to restrict or guide the movement of the sample objects in the measurement volume. The two or more boundary or guiding structures are arranged such that when a solid object having a circular cross section of diameter d is arranged in the measurement volume and the solid object covers the entire first wall of the measurement volume, the solid object is arranged in a self-assembled structure in which a plurality of subsets of the solid objects are each arranged along a respective one of a plurality of straight lines. The illumination system is configured to provide a plurality of illumination light beams, each of which propagates through the substrate along an optical path aligned with a respective one of the plurality of straight lines to illuminate sensing elements adjacent a respective subset of solid objects within the self-assembled structure.

[0065] The sensing device according to the invention offers an alternative way of implementing the method according to the invention compared to the sensor chip according to the invention. Whereas the sensor chip according to the invention offers a boundary structure that allows a plurality of sample objects to be arranged in a self-organizing structure adapted to an array of individual spatially separated sensors on the sensor chip as detailed above, the sensing device according to the invention offers means for selectively illuminating sensing elements, which may for example be uniformly distributed over the entire sensing layer, using a pattern of light adapted to the self-organizing structure of the sample objects in the measurement volume as imposed by the boundary structure. In this way, sensing areas adjacent to the sample objects in the self-organizing structure can for example be selectively activated and / or read out, thereby forming an "illumination-induced" array of sensors adapted to the self-organizing structure.

[0066] The sensor chip of the sensing device may be at least partially similar to any one of the embodiments of the sensor chip according to the invention described herein. For example, the substrate, the measurement volume, and / or the boundary structure of the sensor chip of the sensing device may be similar to the respective elements described above, the description of which is omitted here for brevity. The sensor chip may also comprise additional components, such as droplet generators, microfluidic inlet and / or outlet channels, and / or valves, as described above for the sensor chip according to the invention. In some embodiments, the sensor chip of the sensing device may be a sensor chip according to one of the embodiments of the invention described herein. The sensing elements in the sensing layer may form, for example, an array of spatially separated sensing regions or sensors.

[0067] The sensing layer in which the optically addressable sensing elements are arranged may form at least a part of the first wall, i.e. have a surface exposed to the measurement volume. The sensing layer may for example be a surface layer of a substrate or may be arranged or deposited on a surface layer of a substrate. In other embodiments, one or more layers, for example an optical coating and / or a hydrophilic or hydrophobic coating, may be arranged between the sensing layer and the measurement volume such that the sensing layer is not exposed to the first volume.

[0068] In the context of the present disclosure, an optically addressable sensing element refers to a sensing element that can change its state using light. The sensing elements may be configured, for example, to be optically activated. Each of the sensing elements may be configured, for example, to be switched, using light, from an off state, in which the sensing element does not generate a sensor signal, to an on state, in which the sensing element generates a sensor signal. Additionally or alternatively, the sensing elements may be configured, for example, to be optically read out. Each of the sensing elements may be configured, for example, to be optically excited from a first state to a second state and to generate a sensor signal in response to the excitation. The sensor signal may in particular be an optical sensor signal. The sensor signal may be, for example, the intensity of light emitted by the respective sensing element following optical excitation, for example the fluorescence intensity, or the intensity of light absorbed by the respective sensing element due to optical excitation. In a preferred embodiment, the sensing elements are optically addressable solid-state spin systems, for example nitrogen vacancy centers.

[0069] The boundary structure is arranged such that the solid objects in the self-assembled structure form a plurality of subsets, with the solid objects of a given subset being arranged along respective straight lines. As detailed above, this may also allow for arranging the sample objects, in particular sample objects having a circular cross section with the same diameter d, in a corresponding self-assembled pattern. The solid objects of a given subset may, for example, form a linear chain with each of the solid objects touching or in close proximity to two adjacent solid objects. Each of the subsets may comprise, for example, 5-1000 solid objects, in some cases 10-100 solid objects. The self-assembled structure may include, for example, 2-100, in some cases 5-20 such subsets. Some or preferably all of the straight lines may be parallel to each other, i.e., each subset may be arranged in parallel. In some embodiments, the self-assembled structure may be a uniform close-packing of equal circles or spheres, and the straight lines may be parallel to the fundamental vectors of the corresponding hexagonal lattice. Each of the solid objects in the self-assembled structure may, in some instances, be part of a subset, while in other instances, one or more solid objects in the self-assembled structure may not be part of a subset.

[0070] The illumination system may comprise one or more optical elements, such as beam splitters, diffractive optical elements, reflective coatings, mirrors, waveguides, and / or lenses, to provide the illumination light beams. The illumination system is configured to provide the illumination light beams such that each of the illumination light beams propagates through the substrate along an optical path aligned with a respective straight line and thus with a respective subset of solid objects in the self-assembled structure. The optical paths may extend, for example, such that the optical paths can be projected onto the respective straight lines along a direction perpendicular to the straight lines, i.e., such that they overlap with the straight lines when viewed along a direction perpendicular to the straight lines. In other words, the optical paths may extend in a plane that includes the straight lines, and in particular may be parallel to the straight lines. At least a portion of the optical paths extends through the sensing layer such that the sensing elements can be illuminated by the illumination light beams. Light for generating the illumination light beams may be provided by one or more external light sources, such as lasers. The illumination system may not include a light source in some embodiments. In other embodiments, the illumination system may also comprise one or more light sources for generating the illumination light beams.

[0071] The illumination system may be configured to split the incident light beam into a number of illumination light beams. The incident light beam may be provided, for example, by an external light source or a light source forming part of the illumination system. The illumination system may, for example, comprise one or more beam splitters, each of which may, for example, be configured to split an illumination light beam from the incident light beam and couple the illumination light beams into respective optical paths. The beam splitters may, for example, be non-polarizing beam splitters, which may be configured to split the incident light beam by a partially reflective surface or interface, and / or polarizing beam splitters, which may be configured to split the incident light beam by an interface surface having a polarization-dependent reflectivity. Additionally or alternatively, the illumination light system may comprise one or more diffractive optical elements, each of which is configured to split a light beam, such as the incident light beam, into two or more beams by diffraction.

[0072] Some or all of the optical paths of the illumination light beam may be parallel to one another, and the optical paths may be arranged, for example, with a uniform spacing A1 between adjacent optical paths. The optical paths may in particular be arranged with spacing A1=d or

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[0073] One or more of the optical paths of the illumination light beam, in some cases all of the optical paths of the illumination light beam, may extend through the sensing layer at an angle of less than 10°, preferably less than 5°, with respect to the first wall of the measurement volume. In some embodiments, each of the respective optical paths may comprise a reflection at an upper or lower surface of the sensing layer, e.g. total internal reflection at the first wall of the measurement volume, or a reflection at a reflective coating on the first wall. In other embodiments, each optical path may be parallel to the first wall of the measurement volume.

[0074] Additionally or alternatively, for one or more of the optical paths of the illumination light beam, and in some examples for all of the optical paths of the illumination light beam, the light propagating along the respective optical paths may be sequentially reflected from a first surface above the sensing layer and a second surface below the sensing layer, such that the optical paths intersect the sensing layer within a sensing region. The sensing regions may correspond to portions of the sensing layer in which sensing elements are illuminated by the illumination light beam, and thus may be optically addressed using an illumination system, for example, to activate and / or read out the respective sensing elements. The optical path of the illumination light beam passes sequentially through each of the corresponding sensing regions, such that the sensing elements in these sensing regions may be addressed using a single optical beam. Preferably, each of the sensing regions is adjacent to a respective one of the solid objects in the self-assembled structure, for example, such that the center of the sensing region is aligned with the center of the respective solid object in the self-assembled structure. This may enable, for example, targeted addressing of the sensing elements in the vicinity of the sample object in the corresponding self-assembled structure.

[0075] The reflection at the first surface and / or the second surface may occur, for example, by total internal reflection at the respective surfaces or interfaces. In some embodiments, the illumination system may also comprise a reflective coating on the first surface and / or the second surface, the reflective coating being configured to reflect the illumination light beam. The first surface may be in close proximity to the sensing layer, for example, less than 2 μm, in some cases less than 1 μm, from the top surface of the sensing layer. The distance between the top surface of the sensing layer and the first surface may be selected such that the portions of the respective light paths in the sensing layer before and after the reflection at the first surface are sufficiently close to each other such that a single sensing region is formed, for example, such that the distance between the respective portions is smaller than the diameter of the illumination light beam. The first surface may be, for example, a first wall of the measurement volume and / or may be the top surface of the sensing layer. The second surface may be located at a greater distance from the sensing layer, for example, at a distance of 10 μm to 1000 μm from the bottom surface of the sensing layer, such that the portions of the respective light paths before and after the reflection at the second surface are located outside the sensing layer, thereby allowing the formation of spatially separated sensing regions. The second surface may be, for example, a bottom surface of the substrate. Preferably, the first and second surfaces are parallel to each other.

[0076] In some embodiments, the sensing elements may be distributed uniformly throughout the sensing layer, e.g. such that the density of the sensing elements or the average spacing between adjacent sensing elements is uniform within the sensing layer. Thus, the sensing elements may not only be located in the vicinity of the optical path of the illumination light beam, but also in other parts of the sensing layer. The illumination light beam propagating through the substrate may define sensing regions, i.e. parts of the sensing layer where the sensing elements are illuminated and thus may be addressed by the illumination light beam, e.g. for selective activation and / or readout of the respective sensing elements. As a result of the alignment between the optical path of the illumination light beam and the solid objects in the self-assembled structure, these "illumination-induced" sensing regions also form a pattern adapted to the self-assembled structure. The sensing regions may be, for example, strip-like portions or regions of the sensing layer extending parallel to a subset of the solid objects in the self-assembled structure, or may form an array of spatially separated sensing regions that may match the arrangement of the solid objects in the self-assembled structure.

[0077] In other embodiments, the sensing elements may not be distributed throughout the entire sensing layer, but may be confined to a portion of the sensing layer, for example confined to an array of spatially separated sensing regions, as described above for the sensor chip according to the invention.

[0078] In some embodiments, each of the sensing elements may be configured to generate an optical sensor signal, which may for example be light emitted or transmitted by the respective sensing element. The sensing device may further comprise a photosensitive detector configured to record the sensor signals of the sensing elements, for example by determining the intensity of light emitted or transmitted by one or more of the sensing elements. The photosensitive detector may in particular be configured to record a spatially resolved image of the sensor signals of the sensing elements, i.e. to record the sensor signals of the sensing elements as a function of position in the sensing layer. The photosensitive detector may be configured to determine the intensity of light as a function of position in the sensing layer, for example in a plane parallel to the first wall of the measurement volume. The photosensitive detector may comprise a camera chip with a plurality of photosensitive pixels, such as a CCD or CMOS chip, on which the sensing layer or a part thereof is imaged, for example using a microscope imaging system.

[0079] The sensing device may comprise a controller configured to obtain a spatially resolved image of the sensor signals from the photosensitive detectors. The controller may be implemented in hardware, software or a combination thereof. The controller may comprise, for example, a processor and a memory storing instructions executed by the processor to provide the functionality described herein. The controller may be configured to select, for each of at least a portion of the solid objects in the self-assembled structure, a region of interest in the spatially resolved image, the region of interest including the sensor signals originating from the sensing regions adjacent to the respective solid objects in the self-assembled structure. Thereby, the controller may also be configured to selectively determine the sensor signals associated with a particular sample object in the corresponding self-assembled structure, for example as detailed above for the method according to the invention. The region of interest may, for example, correspond to a portion of the photosensitive detector on which the respective sensing region is imaged. In other examples, the region of interest may be smaller than the sensing region and may, for example, include only the sensor signals originating from a central portion of the respective sensing region. The region of interest may, for example, be a region of a predetermined size around a point in the spatially resolved image associated with the respective solid object or the center of the sample object. The controller may store a list of positions associated with the solid objects in the self-assembled structure for selecting the region of interest. In another example, the controller may be configured to determine the position of each solid or sample object in the measurement volume, e.g. from an image of the respective object in the measurement volume, and select the region of interest accordingly.

[0080] In a preferred embodiment, the sensing element is an optically addressable solid spin system, in particular a diamond color center, for example a nitrogen vacancy center in diamond.As detailed above, the solid spin system may be distributed uniformly throughout the sensing layer, or may be confined to a spatially separated sensing region in the sensing layer.In some cases, the density of the solid spin system in the substrate outside the sensing region may be, for example, at least 100 times, preferably at least 1000 times, the density of the solid spin system in the sensing region.

[0081] The sensing device may further comprise a mount configured to receive the sensor chip, e.g., to hold the sensor chip in a fixed position relative to the lighting system. In some embodiments, the lighting system or part thereof is disposed on the mount, e.g., on a frame of the mount on which the sensor chip is disposed. The mount may be adjustable, e.g., configured to move and / or tilt the sensor chip and / or the lighting system, e.g., to align the sensor chip and / or the lighting system with respect to each other and / or with respect to an incident light beam provided by a light source.

[0082] The present invention further provides a measurement system for parallel probing of multiple samples using a method according to any one of the embodiments described herein. The measurement system comprises a mount configured to receive a sensor chip, the sensor chip comprising a sensing layer disposed in or on a substrate and a measurement volume adjacent to the sensing layer. The sensing layer comprises a plurality of sensing elements, each of which is configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element. The measurement system further comprises a microfluidic unit configured to supply a carrier fluid containing the plurality of sample objects to the measurement volume when the sensor chip is disposed in the mount. The measurement system also comprises a measurement device configured to read out the sensor signal from the sensing elements when the sensor chip is disposed in the mount. The measurement system further comprises a controller, the controller configured to control the microfluidic unit and the measurement device. The controller configured to control the microfluidic unit to control the plurality of sample objects in the measurement volume such that the sample objects form a self-assembled structure in the measurement volume. The controller is further configured to control the measurement device to perform measurements on one or more of the samples while the sample objects are disposed within the self-assembled structure, the measurements on the samples being performed using one or more sensing elements disposed adjacent to each sample object within the self-assembled structure.

[0083] The measurement system may be configured in particular for use with a sensor chip and / or a sensing device according to one of the embodiments described herein. In some examples, the measurement system may also include one or more sensor chips according to one of the embodiments described herein, an illumination system for providing multiple illumination light beams as described above, and / or a sensing device according to one of the embodiments described herein.

[0084] The microfluidic unit may comprise, for example, one or more reservoirs for the carrier fluid and / or the sample fluid, and one or more connectors configured to be connected to input or output ports of the sensor chip for providing or removing the carrier fluid and / or the sample fluid. The microfluidic unit may further comprise one or more pumps for generating a flow of the carrier fluid and / or the sample fluid. In some embodiments, the microfluidic unit may also comprise a droplet generator for preparing the sample objects in the carrier fluid, for example as described above. In other examples, the microfluidic unit may be configured to provide the carrier fluid and the sample fluid separately to the sensor chip, for example to a droplet generator on the sensor chip, or the sample objects may be prepared in the carrier fluid before providing the carrier fluid to the microfluidic unit.

[0085] The measurement device may, for example, comprise a number of measurement channels, each of which may, for example, be associated with a respective sensor or sensing area on the sensor chip and configured to read out a sensor signal from the respective sensor or sensing area. As detailed above, the sensor signal may, for example, be an electrical or optical signal. Thus, each measurement channel may, for example, comprise a voltmeter, an ammeter and / or a light-sensitive detector, for example a photodiode or a photomultiplier. The measurement device may in particular comprise a light-sensitive detector configured to record a spatially resolved image of the optical sensor signal of the sensing element, as described above for the sensing device according to the invention.

[0086] The controller may be implemented in hardware, software, or a combination thereof. The controller may, for example, comprise a processor and a memory that stores instructions executed by the processor to provide the functionality described herein. The controller may, for example, be configured to generate control signals for pumps or valves of the microfluidic unit to control the number of sample objects in the measurement volume. The controller may further be configured to determine the number of sample objects in the measurement volume, for example, by monitoring the flow rate of the carrier fluid and / or the sample fluid, using an optical or electromagnetic droplet detector, and / or using a camera. The controller may be configured to track the sample objects, among others, on the sensor chip. The controller may further be configured to generate a control or trigger signal for the measurement device to initiate measurements on one or more samples once the self-assembled structure is formed. The controller may also be configured to read out the measurement results from the measurement device, which may, for example, be an analog or digital signal that quantifies the sensor signal. In some embodiments, the controller may further be configured to perform some or all of the steps of the method for parallel probing of multiple samples according to any one of the embodiments disclosed herein. The controller may also be configured to provide some or all of the functions of the controller of the sensing device according to the invention described above, i.e. the controller of the sensing device may be at least partially integrated into the controller of the measurement system.

[0087] The present invention further provides a set comprising a measurement system according to any one of the embodiments described herein and a sensor chip according to any one of the embodiments described herein, the measurement system being adapted for use with the respective sensor chip. In particular, the mount of the measurement system can be configured to receive the respective sensor chip. Furthermore, the microfluidic unit can be configured to provide a carrier fluid containing a plurality of sample objects to the measurement volume of the sensor chip, and the measurement device can be configured to read out a sensor signal from each of the sensors in the sensor array of the sensor chip.

[0088] The present invention also provides a set comprising a measurement system according to any one of the embodiments described herein and a sensing device according to any one of the embodiments described herein, the measurement system being adapted for use with a respective sensor chip. In particular, the mount of the measurement system can be configured to receive the sensor chip of the sensing device. The illumination system and the measurement system or a part thereof of the sensing device can be provided as a single integrated system. For example, the illumination system or a part thereof can be arranged on the mount of the measurement system. The microfluidic unit can be configured to provide a carrier fluid containing a plurality of sample objects to the measurement volume of the sensor chip, and the measurement device can be configured to read out a sensor signal from a sensing element on the sensor chip, for example as described above.

[0089] In the following, a detailed description of the invention and its exemplary embodiments is given with reference to the drawings, which show the following schematic diagrams: [Brief description of the drawings]

[0090] [Figure 1a] FIG. 2 is a top view of a sensor chip according to an exemplary embodiment of the present invention. [Figure 1b] FIG. 1b is a side view of the sensor chip of FIG. [Diagram 2]FIG. 2 is a top view of a sensor chip having a hexagonal sensor array according to an exemplary embodiment of the present invention. [Figure 3a] FIG. 2 is a top view of a sensor chip with guiding walls according to an exemplary embodiment of the present invention. [Figure 3b] FIG. 2 is a top view of a sensor chip including a hydrophilic or hydrophobic coating according to an exemplary embodiment of the present invention. [Figure 4] FIG. 1 is a side view of a measurement system in accordance with an exemplary embodiment of the present invention. [Diagram 5] FIG. 1 is a flow diagram of a method for parallel probing of multiple samples according to an exemplary embodiment of the invention. [Figure 6] 1 is a microscope image of multiple microdroplets arranged in a self-assembled periodic structure on a sensor chip according to an exemplary embodiment of the present invention. [Figure 7a] FIG. 2 is a top view of a sensing device according to an exemplary embodiment of the present invention. [Figure 7b] FIG. 7b is a side view of the sensor chip of the sensing device of FIG. 7a. [Figure 8] FIG. 1 is a flow diagram of a method for parallel probing of multiple samples including selection of a subset of sensing elements according to an exemplary embodiment of the invention. [Figure 9] 7b shows a sensor chip of the sensing device of FIG. 7a according to another exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0091] 1a and 1b show schematic diagrams (not to scale) of a sensor chip 100 for parallel probing of multiple samples 112A, according to an exemplary embodiment of the present invention. The sensor chip 100 is shown in a top view in Fig. 1a and in a side view in Fig. 1b.

[0092] The sensor chip 100 comprises a substrate 102, which may be a single-layer or multi-layer substrate, and may comprise or consist of, for example, an optically transparent material such as glass and / or a transparent thermoplastic such as poly(methyl methacrylate) (PMMA). Preferably, the substrate 102 comprises or consists of diamond. The substrate 102 may in particular comprise one or more layers or parts, for example at least the sensing layer 102C, of ​​diamond. In the example of Fig. 1a, 1b, the substrate 102 comprises a lower substrate 102A and an upper substrate or cover 102B, which can be removably placed on the lower substrate 102A, for example to open and close the measurement volume 104 of the sensor chip 100. In other examples, the lower and upper substrates 102 may be permanently attached to each other or may be formed as a single piece. In yet another example, the sensor chip 100 may not comprise a cover 102B. The thickness of the lower substrate 102A perpendicular to the upper surface thereof, i.e., parallel to the Z-axis in FIG. 1b, may be, for example, 10 μm to 5 mm. The cross-sectional area of ​​the sensor chip 100 in the XY-plane in FIG. 1a, which may hereinafter also be referred to as the horizontal plane, may be, for example, 0.01 mm. 2 ~100cm 2 , in some cases, 0.1 cm 2 ~10cm 2 may be also possible.

[0093] The sensor chip 100 comprises a measurement volume 104 formed by a recess in the upper surface of the lower substrate 102A in the example of Fig. 1a, 1b, which may be covered by a cover 102B to seal the measurement volume 104. Thus, the bottom surface of the recess forms a first wall or bottom wall 104-A of the measurement volume 104, and the bottom surface of the cover 102B forms a second wall or top wall 104-B of the measurement volume 104 opposite the bottom wall 104-A. The measurement volume 104 may have a height of, for example, 10 μm to 1 mm, the height of the measurement volume 104 being the distance between the bottom wall 104-A and the top wall 104-B. In the example of Figures 1a, 1b, the measurement volume 104 is a microfluidic channel extending along the X direction, and the width D of the measurement volume 104 perpendicular to the direction of flow in the microfluidic channel may be, for example, 10 µm to 100 µm, and the length of the measurement volume 104 parallel to the direction of flow may be, for example, 100 µm to 10 mm.

[0094] The sensor chip 100 further comprises two inlets or input ports 106A, 106B and an outlet or output port 108, which are in fluid communication with the measurement volume 104 and may be used, for example, to supply or remove a fluid to / from the measurement volume 104. The sensor chip 100 also comprises a droplet generator 110 arranged between the input ports 106A, 106B and the measurement volume 104. The droplet generator 110 is configured to generate microdroplets of a first fluid (e.g., a sample fluid) in a second fluid (e.g., a carrier fluid), in particular monodisperse microdroplets having a uniform size. To this end, the droplet generator 110 may comprise, for example, a T-junction in which a first flow path from the first input port 106A intersects at an angle with a second flow path from the second input port 106B, the outlet of the T-junction being in fluid communication with the measurement volume 104. This may allow for generating micro-droplets of the sample fluid provided at the first input port 106A in the carrier fluid provided at the second input port 106B. In other examples, the droplet generator 110 may have a different design and may be configured to generate micro-droplets, for example, by parallel flow droplet generation, by hydrodynamic flow focusing, and / or by step emulsification. In other embodiments, the sensor chip 100 may not include a droplet generator 110, but a carrier fluid already containing the sample object may be provided to the sensor chip 100 via the input port.

[0095] The measurement volume 104 is configured to receive a carrier fluid containing a plurality of sample objects 112. In the example of Fig. 1a, 1b, the sample objects 112 are microdroplets of sample fluid in the carrier fluid, which are generated by the droplet generator 110, for example, to study the properties of the sample fluid or objects or substances contained therein. In other embodiments, the sample objects 112 may be microbubbles or microparticles, such as microbeads, e.g. agarose beads. To generate the microdroplets 112, the carrier fluid and the microdroplets can be obtained from an emulsion, using a carrier fluid that is immiscible with the sample fluid, e.g. as described in more detail below for the method 500. Additionally or alternatively, surfactants, such as amphipathic molecules, may be mixed into the sample fluid and / or the carrier fluid, such that a shell layer 112B, e.g. a lipid bilayer, is formed around the core 112A of the microdroplet 112, which contains the respective sample, e.g. a certain amount of the sample fluid, as shown in Fig. 1b. The microdroplets 112 may have the same composition or may have different compositions, for example by varying the composition of the sample fluid, for example the concentration of one or more objects or substances in the sample fluid, over time. The physical dimensions of the sample objects or microdroplets 112, such as width or diameter d, may be, for example, between 10 μm and 100 μm.

[0096] The sensor chip 100 further comprises a sensing layer 102C in or on the bottom substrate 102C and adjacent to the measurement volume 104. A plurality of sensing elements 115A, 115B are disposed in the sensing layer 102C, each of which is configured to generate a sensor signal, e.g., an optical sensor signal or an electrical sensor signal, that characterizes a physical observable in the vicinity of the respective sensing element 115A, 115B, e.g., at the position of the respective sensing element 115A, 115B. Each of the sensing elements 115A, 115B can be, for example, an optically addressable solid-state spin system 115A (e.g., a nitrogen vacancy center) or a microelectrode 115B, as shown in the lower inset of FIG. 1b.

[0097] The sensing elements are grouped into multiple spatially separated sensors 114A / 114B for probing the sample 112A, which are indicated by dashed rectangles in Fig. 1a, 1b. Each of the sensors 114A / 114B may be, for example, a sensing region 114A in the sensing layer 102C, which comprises multiple solid-state spin systems 115A and is separated from adjacent sensing regions 114A by a portion of the sensing layer 102C that does not comprise a solid-state spin system or has a smaller density of solid-state spin systems. In another example, each of the sensors 114A / 114B may be a sensor 114B that comprises a single sensing element, such as, for example, a single microelectrode 115B. In some examples, the sensor chip 100 may also include different types of sensors and / or sensing elements, for example a combination of microelectrodes and solid-state spin systems. Hereinafter, the sensors 114A / 114B in the sensing layer 102C will be referred to as sensors 114, and each sensor 114 may be, for example, a sensing area 114A or a sensor 114B as described above. Accordingly, the sensing elements 115A / 115B may also be referred to as sensing elements 115.

[0098] The sensors 114 are arranged in a periodic array on the bottom wall 104-A of the measurement volume 104. In the example of Figures 1a, 1b, the sensors 114 are arranged in a one-dimensional array or linear chain with a spacing a1 between adjacent sensors 114, the spacing a1 being measured between the centers of each sensor 114. A unit cell 116 of the sensor array, i.e., the basic unit in which the array can be formed by successive tiling, can be defined as a square of length a1 centered on each sensor, for example as indicated by the thick dashed line in Figure 1a.

[0099] Each of the sensors 114 is configured to generate a common sensor signal that characterizes a physical observable in the vicinity of the respective sensor 114, e.g., at the position of the respective sensor 114. The common sensor signal of the sensors 114 may, for example, correspond to the sum or average of the sensor signals of the sensing elements 115 of the respective sensors 114, or may correspond to the sensor signal of the sensing element 115 if the respective sensor 114 comprises only a single sensing element. The value of the physical observable characterized by the common sensor signal of the sensors 114 may be sensitive to changes in a sensing volume surrounding the sensor 114, at least a part of which overlaps with a part of the measurement volume 104, and thus may allow probing properties of the sample 112A. In the example of FIG. 1b, the sensor 114 is fully embedded in the lower substrate 102A such that the sensor 114 and the sensing element 115 therein are not exposed to the measurement volume. In other examples, the sensor 114 may also be exposed to the measurement volume 104, for example, such that some or all of the sensing element 115 is exposed to the measurement volume 104. The surface of the sensor 114 or the sensing element 115 may be flush with the top surface of the lower substrate 102A, for example, or may protrude from the top surface of the lower substrate 102A. In some examples, the sensor 114 may also be located on the cover 102B instead of the lower substrate 102A.

[0100] In a preferred embodiment, each of the sensors 114 is a magnetic quantum sensor comprising a plurality of optically addressable solid-state quantum systems 115A arranged in a sensing region 114A, as shown in the lower left inset of FIG. 1b. In particular, a surface layer of the lower substrate 102A adjacent to the measurement volume 104, such as the sensing layer 102C, or the entire lower substrate 102A, is a slab of diamond. In the sensing layer 102C, a plurality of nitrogen vacancy centers are embedded in the diamond crystal structure as sensing elements 115A, thereby forming the sensing region 114A. The NV center may be in a negative charge state, in particular, exhibiting a triplet electronic ground state with a spin of S=1. The spin state of the NV center can be manipulated using microwaves and read out and / or initialized via an optical transition to an excited triplet state, for example, through spin-dependent fluorescence in the excited state. This allows the NV center to be used as a nanoscale magnetometer for measuring magnetic fields, for example, through optically detected magnetic resonance (ODMR).

[0101] In other embodiments, different types of sensing elements may be used, e.g., temperature sensing elements, current sensing elements, voltage sensing elements, inductive sensing elements, and / or capacitive sensing elements. In some examples, each of the sensors 114 may include one or more electrodes 115B, as shown, for example, in the lower right inset of FIG. 1b, which may be exposed to the measurement volume 104.

[0102] The sensor chip 100 comprises two or more boundary or guiding structures configured to restrict or guide the movement of the sample object 112 in the measurement volume 104 in order to align the sample object 112 with the sensor array. In the example of Fig. 1a, 1b, two opposing side walls 104-1, 104-2 extending between the bottom wall 104-A and the top wall 104-B of the measurement volume 104 and which may correspond, for example, to the side walls of a recess in the lower substrate 102A form the boundary or guiding structures. The side walls 104-1, 104-2 extend parallel to each other along the X-axis and are separated by a distance D. The distance D is selected to match the spacing a1 of the sensor array. Additionally, the sidewalls 104-1, 104-2 are positioned such that the sensor 114 is centered between the sidewalls 104-1, 104-2, and thus the sidewalls 104-1, 104-2 are aligned with two opposing edges of each unit cell 116 of the sensor array.

[0103] In this way, when the measurement volume 104 is completely filled with objects such as sample objects 112 having a circular cross section with a diameter d corresponding to the spacing a1, for example, such that the entire bottom wall 104-A is covered by the sample objects 112, the side walls 104-1, 104-2 arrange the sample objects 112 in a self-assembled structure in which each of the sample objects 112 is aligned with a respective one of the sensors 114, for example, such that the sample objects 112 are centered within their respective unit cells 116, as shown in FIG. 1a. In the self-assembled structure, the sample objects 112 form a close packing of equal circles, each of the sample objects 112 being in contact with the side walls 104-1, 104-2 as well as the other sample objects 112. In some examples, the sample objects 112 can have a spherical shape as shown in FIG. 1a, 1b, and the self-assembled structure can correspond to a close packing of equal spheres. In the self-assembled structure, interactions between the sample objects 112 and the side walls 104-1, 104-2, and among the sample objects 112 themselves, prevent all sample objects 112, except for those placed at the edges of the self-assembled structure, from moving within the measurement volume 104, thereby ensuring a stable positioning with respect to the respective sensor 114. In some embodiments, the sensor chip 100 may further comprise boundary or guiding structures (not shown) that prevent the self-assembled structure or the sample objects placed at its edges from moving along the flow direction in the measurement volume 104.

[0104] In the example of FIG. 1b, the height of the measurement volume 104 also corresponds to the interval a1 to ensure that the spherical sample object 112 contacts both the bottom wall 104-A and the top wall 104-B, thereby adjacent to the sensor 114 along the Z direction in FIG. 1b, which may also be referred to as the vertical direction. In other examples, the height of the measurement volume 104 may be larger than the interval a1, or the measurement volume 104 may be open from the top, for example, when the cover 102B is not present. In such a case, the position of the sample object 112 along the vertical direction can be controlled, for example, by controlling the fill level of the carrier fluid in the measurement volume 104 and / or by using a carrier fluid having a lower density than the sample object 112. In some examples, the sample object 112 may not be spherical, but may still have a circular cross section with a diameter d in the XY plane of FIG. 1a, for example, a spheroid, an ellipse, or a cylindrical shape. The height of the measurement volume 104 may be smaller than the interval a1, for example. In yet other examples, the sample objects 112 in the self-assembled structure may not have a circular cross-section, but the self-assembled structure may nevertheless resemble a close packing of equal circles, for example, in the sense that the centers of the sample objects and / or the contact points between the sample objects are aligned with corresponding points in an ideal close packing of equal circles.

[0105] FIG. 2 shows a schematic diagram (not to scale) in top view of a sensor chip 200 for parallel probing of multiple samples according to another exemplary embodiment of the present invention.

[0106] The sensor chip 200 is similar to the sensor chip 100 of Fig. 1a, 1b and also comprises a substrate 102, in which a measurement volume or measurement chamber 104 is arranged to receive a carrier fluid containing a plurality of sample objects 112, such as microdroplets or cells. In the example of Fig. 2, the measurement volume has a rectangular shape with a first pair of opposing side walls 104-1, 104-2 separated by a first distance D1 and a second pair of opposing side walls 104-3, 104-3 separated by a second distance D2. The first and second distances may be, for example, between 100 μm and 2 mm, respectively. The bottom wall of the measurement volume 104 extends between the side walls 104-1 to 104-4, and the upper surface of the bottom wall exposed to the measurement volume 104 is a flat surface without any protrusions or depressions. In some embodiments, the bottom wall and / or one or more of the side walls 104-1 to 104-4 may be coated with a hydrophilic or hydrophobic coating, for example to promote or prevent wetting of the respective surface by the carrier fluid. The respective coating may in particular be a uniform coating applied to the entire surface and not patterned or structured in any way.

[0107] Similar to the sensor chip 100, the sensor chip 200 comprises two input ports 106A, 106B, an output port 108, and a droplet generator 110 arranged between the input ports 106A, 106B and the measurement volume 104. The sensor chip 200 further comprises a microfluidic inlet channel 202 arranged between the droplet generator 110 and the measurement volume 104 for providing the measurement volume 104 with a carrier fluid containing microdroplets 112 generated by the droplet generator 110. The sensor chip 100 also comprises a microfluidic outlet channel 204 connecting the measurement volume 104 to the output port 108. A microfluidic valve 206 is arranged along the outlet channel 204, the valve 206 being configured to adjust the cross-sectional area of ​​the outlet channel 204, for example to selectively prevent the sample object 112 from leaving the measurement volume 104 via the outlet channel 204 while allowing the flow of the carrier fluid through the outlet channel 204.

[0108] A plurality of sensors 114 are arranged in a two-dimensional periodic array on the bottom wall of the measurement volume 104, each of the sensors 114 comprising one or more sensing elements (not shown), e.g., as described above with reference to Figures 1a and 1b. In the example of Figure 2, the two-dimensional periodic array has a spacing a between adjacent sensors 114. h The hexagonal lattice has a basis vector

number

number

[0109] The side walls 104-1 to 104-4 of the measurement volume 104 constitute boundaries or guiding structures configured to limit or guide the movement of the sample object 112 within the measurement volume 104. The distances D1 and D2 are the distances between the sensor arrays a his selected such that a uniform close-packing of equal circles or spheres (e.g., cylindrical or spherical sample objects 112) with diameters corresponding to can be placed in the measurement volume 104 with the outermost circles / spheres in contact with the side walls 104-1 to 104-4. When the entire bottom wall of the measurement volume 104 is covered by circles / spheres as shown in FIG. 2, the position of each of the circles / spheres is fixed by contact with the other circles / spheres surrounding the respective circle / sphere or by contact with adjacent circles / spheres as well as one or more of the side walls 104-1 to 104-4. Thus, except for the circles / spheres located at the orifices of the inlet and outlet channels 202, 204, none of the circles / spheres can move without moving at least one other circle / sphere, i.e., the translational degrees of freedom of the circles / spheres parallel to the bottom wall of the measurement volume 104 are eliminated, and the resulting self-assembled structure is stable. In some cases, the inlet and outlet channels 202, 204 may also be filled with spheres to prevent the circles / spheres at the orifices of the inlet and outlet channels 202, 204 from moving.

[0110] In the example of FIG. 2, the distance D1 between the number 104-1 and the side wall 104-2 is expressed by the fundamental vector of the sensor array

number

number

number

number

number

number

[0111] The hexagonal lattice on which the sensors 114 are arranged is specifically adapted to arrange objects with circular cross-sections, such as spheres, in a uniform close-packing of equal circles or spheres in two dimensions, which also constitutes a hexagonal lattice. Furthermore, the positions of the side walls 104-1 to 104-4 are selected such that the hexagonal lattice on which the sensors 114 are arranged and the close-packing hexagonal lattice of equal circles or spheres are aligned with each other, e.g. such that the unit cells of the two lattices are aligned with each other in a line of sight perpendicular to the bottom wall of the measurement volume 104. In this way, each of the circles / spheres or sample objects 112 in the measurement volume can be arranged above a respective one of the sensors 114 such that, for example, the edge of the respective unit cell 116 is tangent to the circumference of the sphere in a line of sight perpendicular to the bottom wall, and the center of the circle / sphere is aligned with the center of the corresponding sensor 114. This means that, for example, each of the outermost sensors 114 of the array is located at a distance a corresponding to the radius of the circle / sphere from the respective side wall. h This can be achieved by arranging the side walls 104-1 to 104-4 such that they are separated by .gtoreq.1 / 2.

[0112] 3a and 3b show schematic diagrams (not to scale) in top view, respectively, of a sensor chip 300 and a sensor chip 310 for parallel probing of multiple samples according to another exemplary embodiment of the present invention. The sensor chips 300, 310 are similar to the sensor chip 200 and also comprise a substrate 102 having a measurement volume 104, a droplet generator 110 having two input ports, and an output port 108.

[0113] The sensor chip 300 of Fig. 3a comprises a rectangular measurement volume 104 formed by a bottom wall having a flat upper surface extending between two pairs of opposing side walls. A number of guide walls 302 are disposed on the bottom wall, which extend upward from the upper surface of the bottom wall, for example, towards a top wall or opening of the measurement volume 104. In some embodiments, the tops of the guide walls 302 may contact the top wall, i.e., the guide walls 302 may extend from the bottom wall to the top wall. The guide walls 302 are parallel to the pair of opposing side walls and are disposed in an alternating zigzag pattern. In the alternating zigzag pattern, every other guide wall 302 contacts a first sidewall 104-3 of the other pair of opposing sidewalls of the measurement volume 104 while leaving an opening or cutout adjacent a second sidewall 104-4 of the measurement volume 104 opposite the first sidewall 104-3, and the remaining guide walls 302 contact the second sidewall 104-4 while leaving an opening or cutout adjacent the first sidewall 104-3. The guide walls 302 thereby divide the measurement volume 104 into a serpentine flow path that extends from an entrance of the measurement volume 104 to an exit of the measurement volume 104.

[0114] At the bottom wall of the measurement volume 104, a plurality of sensors 114 are arranged in a two-dimensional rectangular array with a first spacing a1 along the X direction of FIG. 3a and a second spacing a2 along the Y direction, the second spacing being greater than the first spacing. Each of the sensors 114 along the circumference of the sensor array, i.e., the outermost sensor of the sensor array, is arranged at a distance a1 / 2 from a side wall of the measurement volume 104. The side walls 104-3, 104-4 are separated by a distance D2 equal to an integer multiple of a1, where D2=M·a1, where M may be, for example, 10-100. Furthermore, the guiding wall 302 is arranged such that the serpentine channel has a width equal to the first spacing a1 and the centerline of the channel is aligned with the center of the sensor 114, for example, similar to the sensor chip 100 of FIG. 1. In this way, objects with a circular cross section, such as spherical or cylindrical sample objects 112 in the measurement volume 104, can be confined to close-packing of equal circles or spheres in a rectangular lattice, as opposed to a uniform close-packing hexagonal lattice of equal circles or spheres as in FIG. 2, and thus match the rectangular lattice of the sensor array. This can be advantageous, for example, to reduce crosstalk between the sensors 114 due to the increased spacing a2, as well as to facilitate the formation of corresponding self-assembled structures of the sample objects 112 due to the additional confinement provided by the guiding walls 302. In some embodiments, the sensor chip 300 may comprise a hydrophilic or hydrophobic coating instead of or in addition to the guiding walls 302, for example, similar to the sensor chip 310.

[0115] The sensor chip 310 of Fig. 3b comprises a measurement volume 104 having a rectangular central portion 104b disposed between a proximal portion 104a and a distal portion 104c of the measurement volume 104. The central portion 104b is formed by two opposing parallel sidewalls extending parallel to the X-axis of Fig. 3b, and the proximal portion 104a and the distal portion 104c are tapered such that the widths of the proximal portion 104a and the distal portion 104c perpendicular to the sidewalls of the central portion 104b, i.e. along the Y-direction of Fig. 3b, increase from the entrance and exit orifices of the measurement volume 104, respectively, towards the central portion 104b.

[0116] In the central portion 104b of the measurement volume 104, a number of coatings 312 are disposed on the bottom wall of the measurement volume 104. The coatings 312 may be, for example, hydrophilic or hydrophobic coatings on the top surface of the bottom wall and may be configured, for example, to prevent wetting of the respective areas by the carrier fluid containing the sample object 112, thereby forming a boundary or guiding structure that makes a part of the top surface of the bottom wall inaccessible to the carrier fluid and the sample object 112. The coatings 312 extend parallel to the side walls of the central portion 104b and define a number of parallel flow paths extending through the central portion 104b from the proximal portion 104a to the distal portion 104c. In some embodiments, the sensor chip 310 may also comprise guiding walls instead of or in addition to the coatings 312, for example, similar to the sensor chip 300.

[0117] On the bottom wall of the measurement volume 104, a number of sensors 114 are arranged in a two-dimensional rectangular array with first and second spacings a1, a2, similar to the sensor arrangement of the sensor chip 300 of FIG. 3a, for example, such that the sensor array 114 covers the entire central portion 104b. The coating 312 is arranged such that each of the channels has a width corresponding to the first spacing a1, and the sensors 314 along each channel are centered with respect to the centerline of the respective channel. The angle between the sidewalls of the tapered proximal portion 104a, the angle between the sidewalls of the tapered distal portion 104c, and the length of the channels are selected such that when the measurement volume 104 is filled with objects having a circular cross section, such as spherical or cylindrical sample objects 112, the sample objects 112 form a self-organized close packing, with each sample object 112 in the central portion 104b being located above a respective one of the sensors 114. The proximal portion 104a and the distal portion 104c may not have a sensor 114, but the sample objects 114 placed therein may ensure accurate positioning of the sample objects 114 in the central portion 104b relative to the sensor 114 by forming a close packing of circles or spheres that prevents the sample objects 114 at the end portions of the flow path from moving, and in particular from exiting the flow path.

[0118] FIG. 4 shows a schematic diagram (not to scale) of a measurement system 400 for parallel probing of multiple samples in side view according to an exemplary embodiment of the present invention. The measurement system 400 may be configured for use with a sensor chip according to any one of the embodiments described herein, such as one or more of the sensor chips 100, 200, 300, and 310. Additionally or alternatively, the measurement system 400 may also be configured for use with a sensing device according to any one of the embodiments described herein, such as the sensing device 700 of FIG. 7a, FIG. 7b described below. The measurement system 400 may be used to perform a method for parallel probing of multiple samples according to any one of the embodiments described herein, such as the method 500 described below with reference to FIG. 5, or the method 800 described below with reference to FIG. 8.

[0119] The measurement system 400 comprises a mount 402 configured to receive a sensor chip 404. The sensor chip 404 comprises a sensing layer 102C disposed in or on a substrate, the sensing layer 102C comprising a plurality of sensing elements (not shown). The sensing elements may form a periodic array of sensors 114, e.g. as detailed above with reference to Figs. 1a, 1b, e.g. as shown in Fig. 4. The sensor chip 404 further comprises a measurement volume 104 adjacent to the sensing layer 102C. In some embodiments, the sensor chip 404 may correspond to one of the sensor chips 100, 200, 300, and 310 described above. In other embodiments, the sensor chip 404 may correspond to the sensor chip 704 of the sensing device 700 described below with reference to Fig. 7. The mount 402 is configured to hold the sensor chip 404 and may comprise, for example, a means for removably attaching the sensor chip 404 to the mount 404, e.g. one or more fastening clips or screws. In some embodiments, the mount 402 may also be configured to move the sensor chip 404 along one or more directions and / or tilt the sensor chip 404 about one or more axes, e.g., for alignment purposes. In some embodiments, the mount 402 may be similar to the mount 702 of the sensing device 700 of Figures 7a, 7b.

[0120] The measurement system 400 further comprises a microfluidic unit 406 configured to supply a carrier fluid containing a plurality of sample objects 112 to the measurement volume 104 of the sensor chip 404. In the example of FIG. 4, the microfluidic unit 406 is configured to be connected to an input port 106 of the sensor chip 404 in fluid communication with the measurement volume 104. The microfluidic unit 406 may comprise one or more reservoirs (not shown) for storing fluids, such as, for example, a carrier fluid and a sample fluid. The microfluidic unit 406 may also comprise one or more pumps (not shown) for supplying the respective fluids to the sensor chip 404. The microfluidic unit 406 may further comprise a droplet generator (not shown) for generating microdroplets of the sample fluid in the carrier fluid, for example similar to the droplet generator 110 of the sensor chip 100 of FIG. 1. In other examples, the microfluidic unit 406 may not comprise a droplet generator, but may be configured to supply, for example, the carrier fluid and the sample fluid to a droplet generator on the sensor chip 404. The microfluidic unit 406 may be further configured to be connected to the output ports 108 A, 108 B of the sensor chip 404 , for example, to remove the carrier fluid and the sample object 112 from the sensor chip 404 .

[0121] The measurement system 400 comprises a measurement device 408 configured to read out an electrical or optical sensor signal from a sensing element on the sensor chip 404. The measurement system 400 may be configured, for example, to read out a common sensor signal from each of the sensors 114 in the sensor array of the sensor chip 404. The measurement device 408 may be configured, for example, to be connected to an electrical connector (not shown) on the sensor chip 404 to provide an electrical connection between the sensors 114 and the measurement device 408. The measurement device 408 may comprise a number of detectors or measurement elements 410, each of which may be configured to read out a common sensor signal from a respective one of the sensors 114. Each of the measurement elements 410 may comprise, for example, a voltmeter and / or an ammeter for measuring a voltage and a current, respectively, associated with each sensor 114. In other embodiments, the measurement element 410 may be a photosensitive detector, for example, as described in more detail below.

[0122] The measurement system 400 also includes a controller 412, which may be implemented in hardware, software, or a combination thereof. The controller 412 may include, among other things, a processor (not shown) and a memory (not shown), where the memory stores instructions that may be executed by the processor to provide the functionality described herein. The controller 412 may include, for example, a central processing unit (GPU), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a non-volatile memory, a volatile memory, a microcontroller, and / or a system on a chip (SoC). Additionally or alternatively, the controller 412 may also include other analog and / or digital electronic circuits. In some examples, the measurement device 408 may be at least partially integrated into the controller 412.

[0123] The controller 412 is configured to control the microfluidic unit 406 to control the plurality of sample objects 112 in the measurement volume 104, for example by providing control signals to pumps and / or valves of the microfluidic unit 406 to generate a flow of carrier fluid containing the sample objects 112 into the measurement volume 104. The controller 412 is configured in particular to control the microfluidic unit 406 to control the number of sample objects 112 in the measurement volume 104, whereby the sample objects 112 form a self-assembled structure in the measurement volume 104, for example a self-assembled structure in which each sample object 112 is disposed adjacent to each of the sensors 114, as will be described in more detail below with respect to method 500. The controller 412 is further configured to control the measurement device 408 to perform measurements on one or more of the samples 112A while the sample objects 112 are disposed in the self-assembled structure, the measurements on the samples being performed using one or more sensing elements disposed adjacent to each sample object in the self-assembled structure, for example as will be described in more detail below with respect to methods 500 and 800. In some embodiments, the controller 412 may be configured to perform some or all of the steps of a method for parallel probing of multiple samples according to any one of the embodiments described herein, such as method 500 and / or method 800.

[0124] In the example of FIG. 4, the sensor 114 on the sensor chip 404 is a magnetic quantum sensor, in particular a magnetic quantum sensor including an optically addressable solid-state quantum system, such as a nitrogen vacancy center in diamond, as detailed above for the sensor chip 100 of FIG. 1a, FIG. 1b. To manipulate the solid-state quantum system, for example to optically excite the solid-state quantum system, the measurement system 400 is configured for use with one or more light sources 414, in particular lasers, configured to generate light at one or more absorption wavelengths of the solid-state quantum system to illuminate the sensor 114. In some embodiments, the one or more light sources 414 may be provided as independent units or may be part of the measurement system 400. The measurement system 400 may further comprise an illumination system (not shown) configured to couple the light beams generated by the one or more light sources 414 into an optical illumination path that extends through the sensor chip 404 and intersects some or all of the sensors 114 in sequence, so that, for example, the solid-state quantum systems in each of the sensors 114 can be excited with a single light beam that passes through the sensors 114 one after the other. Along the illumination path, the light may be reflected, for example, from the surfaces of the sensor chip 404, for example by total internal reflection and / or at a reflective coating on the respective surface. In some examples, the illumination system of the measurement system 400 may be similar to the illumination system 706 of the sensing device 700. The measurement system 400 may include additional components for manipulating the solid-state quantum system, for example, a magnet (not shown) for applying a bias magnetic field to the sensor chip 404, and / or a microwave and / or radio frequency antenna (not shown) for applying a microwave or radio frequency signal to the sensor chip 404.

[0125] In this example, the measurement device 408 is a multi-channel photodetector comprising a plurality of light-sensitive elements as the measurement elements 410. Each of the light-sensitive elements 410 is configured to determine the intensity of light incident on the respective element and may comprise, for example, one or more photodiodes or photomultipliers, or one or more pixels on a CCD or CMOS chip. Each of the light-sensitive elements 410 is associated with a respective one of the sensors 114, and the measurement system 400 may comprise an imaging system (not shown) configured to collect light emitted by a solid-state spin system in the sensor 114 and image the light onto the respective light-sensitive element 410. In some embodiments, the measurement device 408 may comprise a camera chip with a plurality of light-sensitive pixels, and the controller 412 may be configured to select a subset or region of interest from the plurality of light-sensitive pixels as the respective light-sensitive element 410 for each of the sensors 114, for example, as detailed below for the sensing device 700 of FIG. 7 and the method 800 of FIG. 8.

[0126] The measurement system 400 further comprises a camera 416, which is arranged opposite the measurement device 408 in the example of FIG. 4. The camera 416 is configured to take an image of the sample object 112 on the sensor chip 404, which may be used, for example, to track the sample object 112 on the sensor chip 404 and / or to monitor the formation of a self-assembled structure of the sample object 112 in the measurement volume 104. In some examples, the controller 412 may be configured to automatically track the sample object 112 on the sensor chip 404 using the camera 416, for example, using computer vision techniques. In other examples, the controller 412 may be configured to provide the image obtained from the camera 416 to a user for manual tracking and / or monitoring. In some embodiments, the measurement device 408 may also be used as a camera to take an image of the sample object 112.

[0127] In the example of FIG. 4, the sensor chip 404 further comprises a sorting unit 418 arranged along the outlet flow path of the sensor chip 404 and configured to sort the sample objects 112, for example by selectively redirecting the sample objects 112 to one of the two output ports 108A, 108B of the sensor chip 404. The sorting unit 418 may comprise one or more microfluidic elements, such as, for example, one or more electrodes for generating an electric field, one or more inductive elements for generating a magnetic field, one or more optical elements or light sources for generating an optical potential, and / or valves and / or flow paths for generating a bypass flow. The controller 412 may be configured to control the sorting unit 418, and in particular to control the sorting unit 418 to classify the sample objects 112 based on the measurement results obtained using the sensor 114, for example by diverting the sample objects 112 associated with a measurement value above a threshold to the first output port 108A and the sample objects 112 associated with a measurement value below the threshold to the second output port 108B.

[0128] FIG. 5 shows a flow diagram of a method 500 for parallel probing of multiple samples according to an exemplary embodiment of the present invention. The method 500 can be implemented, for example, using one of the sensor chips 100, 200, 300, 310, 404, 704, using the measurement system 400, and / or using the sensing device 700. In the following, the method 500 is described using the sensor chip 200 and the system 400 as a non-limiting example for illustration. The method 500 is not limited to the order of execution shown by the flow diagram of FIG. 5. As long as it is technically feasible, the method 500 may be performed in any order, and its steps may be performed at least partially simultaneously (e.g., steps 504, 506, and 508 described below).

[0129] The method 500 includes, at step 502, providing a sensor chip having a sensing layer disposed in or on a substrate and a measurement volume adjacent to the sensing layer, the sensing layer comprising a plurality of sensing elements. For example, a sensor chip may be provided, such as the sensor chip 200, comprising a periodic array of sensors 114 disposed on the substrate 102 and a measurement volume 104 adjacent to the sensor array. The sensor chip 200 may be attached, for example, to a mount 402 of the measurement system 400. In an embodiment in which the sample 112A or sample object 112 has a predetermined size, for example, when probing a cell or microdroplet of a predetermined size, the spacing of the sensors 114 on the sensor chip 200 may be, for example, a spacing a h By providing a sensor chip 200 whose dimensions correspond to the physical dimensions of the sample object 112 , the sensor chip 200 may be specifically adapted to the sample 112 A or sample object 112 .

[0130] In step 504, a carrier fluid containing a plurality of sample objects 112 is provided to the measurement volume 104 of the sensor chip 200. Each of the sample objects 112 has or forms a respective sample 112A, which may be a quantity of sample fluid, such as a biological sample fluid, which may have a biological sample, such as proteins, DNA, bacteria, cells or parts thereof, or a chemical sample fluid, which may have one or more reagents and / or products of a chemical reaction. In one example, each of the sample objects 112 is a microdroplet containing cells or bacteria in a sample fluid, the cells or bacteria being configured to produce a substance, such as ethanol. The method 500 may be used to evaluate how efficient the cells or bacteria are in producing a substance, for example to select the most efficient cells or bacteria from a plurality of cells or bacteria. The measurement performed in step 508 may be used to determine the concentration of the substance in the microdroplet. A solid-state spin system, such as a nitrogen vacancy center, may allow for determining the concentration of ethanol in the microdroplet, for example, by nuclear magnetic resonance spectroscopy.

[0131] Providing a carrier fluid containing a plurality of sample objects 112 may in particular comprise generating a plurality of microdroplets of the sample fluid in the carrier fluid, for example using the droplet generator 110 of the sensor chip 200 or a droplet generator of the microfluidic unit 406. In this example, the microdroplets may constitute the sample objects 112. For this purpose, a carrier fluid may be used that is immiscible with the sample fluid. The sample fluid may for example be an aqueous solution or suspension, and the carrier fluid may be an oil (or vice versa), for example a hydrocarbon oil (for example hexadecane), a fluorocarbon oil (for example octadecafluorodecahydronaphthalene or 1-(1,2,2,3,3,4,4,5,5,6,6-undecafluorocyclohexyl)ethanol), a silicone oil, or a mineral oil, as described for example in EP 2 270 236 B1. In another example, the sample fluid may be a first oil and the carrier fluid may be a second oil that is immiscible with the first oil, such as a silicone oil and a mineral oil, or a hydrocarbon oil and a fluorocarbon oil. To stabilize the microdroplets, surfactants such as amphiphilic compounds, such as polyethylene glycol-perfluoropolyether (PEG-PFPE) block copolymer fluorinated surfactants, Octoxynol 9 (C), as described in J.-L. Baret, Lab Chip, 2012, 12, 422-433, are used. 14 H 22 O(C2H4O) n , Triton X-100), sodium dodecyl sulfate (SDS), sorbitan monooleate (C 24 H 44 O6, Span 80), and glyceryl monooleate (C 21 H 40 One or more of surfactants (e.g., 04, monoolein) can be added to the sample fluid and / or carrier fluid. The surfactant can form a shell layer 112B around the core 112A of each microdroplet, thereby, for example, preventing the microdroplets from coalescing. The physical dimensions of the microdroplets can vary, for example, by the diameter of the microdroplets being spaced apart by a distance of 10 mm. hThe spacing of the sensor array of the sensor chip 200 may be adapted to correspond to the spacing of the sensor array of the sensor chip 200. The size of the microdroplets may be controlled, for example, by adjusting the flow rate of the carrier fluid and / or the sample fluid in the droplet generator and / or by adjusting the composition of the carrier fluid and / or the sample fluid.

[0132] In step 506, the plurality of sample objects 112 in the measurement volume 104 are controlled such that the sample objects 112 form a self-assembled structure, for example a self-assembled periodic structure, in the measurement volume 104. In the self-assembled structure, each sample object 112 may be disposed, for example, adjacent to each of the sensors 114 on the sensor chip 200. For example, a flow of carrier fluid containing the microdroplets 112 may be generated through the inlet channel 202 to supply the microdroplets 112 to the measurement volume 104, thereby continuously filling the measurement volume 104. At the same time, the carrier fluid may be removed from the measurement volume 104 through the outlet channel 204, and the valve 206 may be set so that the microdroplets 112 cannot pass through the valve 206. In this way, the number of microdroplets 112 in the measurement volume 104 may be increased stepwise.

[0133] As the number of microdroplets 112 in the measurement volume 104 increases, the microdroplets 112 can contact each other as well as with boundary structures in the form of sidewalls 104-1 to 104-4. Interactions between the microdroplets 112 themselves and between the microdroplets 112 and the sidewalls 104-1 to 104-4 result in the formation of a self-organized close packing as shown in Figure 2 when the entire bottom wall of the measurement volume 104 is covered by the microdroplets 112. As detailed above with reference to Figure 2, the sensors 114 in the array are arranged in a hexagonal lattice that is adapted to the arrangement of circles or spheres with uniform close packing of equal circles / spheres, and the sidewalls 104-1 to 104-4 are arranged such that the self-organized close packing of the microdroplets 112 is aligned with the sensor array, e.g., such that each of the microdroplets 112 in the measurement volume 104 is located above a respective one of the sensors 114. In this self-assembled periodic structure, each microdroplet 112 is fixed in its respective position because adjacent microdroplets 112 and sidewalls 104-1 to 104-4 prevent the microdroplets 112 from moving parallel to the bottom wall of the measurement volume. In some embodiments, the microdroplets 112 may include a monolayer of amphipathic molecules, e.g., a lipid monolayer, as the shell layer 112A, and a bilayer of amphipathic molecules, e.g., a lipid bilayer, may be formed when adjacent microdroplets 112 contact each other. This may further stabilize the self-assembled periodic structure formed in the measurement volume 104.

[0134] In step 508, while the sample objects 112 are placed in the self-assembled structure, measurements are performed on one or more of the samples 112A, in some embodiments on all of the samples 112A, the measurements on the samples 112A being performed using one or more sensing elements 115 arranged adjacent to the respective sample objects 112 in the self-assembled structure. The measurements on the samples 112A may be performed, for example, using sensors 114 on the sensor chip 200, adjacent to which the respective sample objects 112 are placed in the self-assembled structure. The measurements on the one or more samples 112A may be performed in parallel, for example by reading out the measurement signals from each of the sensors 114 simultaneously. The sample objects 112 in the self-assembled structure may be stationary during the measurements, i.e. not moved relative to the sensors 114. This may also allow the measurements to be repeated multiple times and / or multiple different measurements to be performed while the sample objects 112 remain adjacent to their respective sensors 114.

[0135] As detailed above with reference to Figures 1a, 1b, the sensor 114 may in particular be a magnetic quantity sensor and may include an optically addressable solid-state quantum system 115A, for example a nitrogen vacancy center in diamond, as a sensing element 115. Thus, performing a measurement may include illuminating the sensor 114 to optically polarize the solid-state quantum system 115A, applying one or more microwave and / or radio frequency pulses to the sensor 114 to manipulate the state of the solid-state quantum system 115A, illuminating the sensor 114 to optically excite the solid-state quantum system 115A, and / or performing an optical readout of the state of the solid-state quantum system 115A, for example by detecting an optical signal, such as a fluorescence intensity, emitted by the solid-state quantum system 115A in the sensor 114. The optically addressable solid-state quantum system may be used, for example, to perform nuclear magnetic resonance (NMR) spectroscopy.

[0136] The method 500 may further comprise rinsing the sensor chip 200, in particular the measurement volume 104, e.g. after performing the measurement in step 508. For this purpose, the measurement volume 104 may be rinsed, e.g. with water or a buffer solution, e.g. to remove sample objects 112 from the measurement volume 104. The method 500 may then be repeated using the same sensor chip 200, e.g. to probe another set of samples.

[0137] FIG. 6 shows a microscope image of a plurality of microdroplets 112 arranged in a self-assembled periodic structure in a measurement volume 104 of a sensor chip according to an exemplary embodiment of the invention. The measurement volume 104 comprises two opposing side walls 104-1, 104-2 separated by a distance D=1300 μm. The measurement volume 104 is filled with monodisperse microdroplets 112 of a sample fluid comprising water in a carrier fluid comprising a fluorocarbon oil, the microdroplets 112 having a diameter d=104±2 μm. As a result of surface-surface interactions between the microdroplets 112, the microdroplets 112 are arranged in a self-assembled periodic structure, i.e., a uniform close-packing of equal spheres forming a lattice with a hexagonal unit cell 116. The distance D between the side walls 104-1, 104-2 is selected such that 14 linear chains of microdroplets 112 in the uniform close-packing of equal spheres can be arranged in the measurement volume 104, i.e., N=13,

number

[0138] Figures 7a and 7b show schematic diagrams (not to scale) of a sensing device 700 for parallel probing of multiple samples, according to an exemplary embodiment of the invention. Figure 7a shows the sensing device 700 in a top view, and Figure 7b shows the sensor chip 704 of the sensing device 700 in a side view.

[0139] The sensing device 700 comprises a mount 702 configured to receive the sensor chip 704 of the sensing device 700. The mount 702 may comprise, for example, a frame having a recess or notch in which the sensor chip 704 can be positioned. The frame may be made of or include, for example, metal, glass, plastic, or a combination thereof, and is preferably configured to hold the sensor chip 704 such that the top and bottom surfaces of the sensor chip 704 are accessible, particularly for microscopic imaging. In some embodiments, the mount 702 may be similar to the mount 402 of the measurement system 400 of FIG. 4.

[0140] The sensor chip 704 comprises a substrate 102, which may be, for example, a slab of diamond. In or on the substrate 102, a measurement volume 104 is formed for receiving a carrier fluid containing a plurality of sample objects 112, for example as detailed above for the sensor chip 100 of Figs. 1a, 1b. The substrate 102 comprises a plurality of optically addressable sensing elements 115A arranged in a sensing layer 102C adjacent to the measurement volume 104. The sensing layer 102C may be, for example, a surface layer of the substrate 102C forming a first or bottom wall 102-A of the measurement volume 104, as shown in Fig. 7b. In the example of Fig. 7b, the sensing elements 115A are optically addressable solid-state spin systems, in particular nitrogen vacancy centres embedded in the diamond crystal structure of the sensing layer 102C. The depth of the sensing layer 102C perpendicular to the bottom wall 104-A of the measurement volume 104 may be, for example, 5 μm to 10 μm.

[0141] Preferably, the NV centers are distributed throughout the sensing layer 102C, which facilitates the manufacture of the sensor chip 704. The density of the NV centers in the sensing layer 102C may be, for example, uniform, e.g., 10 15 cm -3 ~10 18 cm -3 , in one example, 10 16 cm -3 ~10 17 cm -3 In other examples, the NV centers may be confined to spatially separated sensing regions 114A, which may form, for example, an array of sensors, as detailed above for the sensor chip 100 of Figures 1a, 1b and the sensor chip 200 of Figure 2. The density of NV centers in the sensing region 114A may be, for example, at least 100 times, and in some examples at least 1000 times, greater than the density of NV centers in the sensing layer 102C outside the sensing region 114A.

[0142] The sensor chip 704 further comprises a number of boundary structures configured to limit or guide the movement of the sample object 112 in the measurement volume 104. In the example of Fig. 7a, the boundary structures are side walls 104-1, 104-2, 104-3, 104-4 of the measurement volume 104, which form a rectangular enclosure for the carrier fluid and the sample object 112 contained therein. The distance between the opposing side walls is selected such that a uniform close packing of equal circles or spheres with a diameter d can be arranged in the measurement volume 104, the outermost circles or spheres being in contact with the side walls 104-1, 104-2, 104-3, 104-4 and thus preventing any movement of the circles or spheres parallel to the bottom wall 104-A. The side walls 104-1, 104-2, 104-3, 104-4 may for example be arranged similarly to the side walls of the measurement volume on the sensor chip 200 of Fig. 2. This allows the formation of a corresponding self-assembled structure of the sample object 112 having a circular cross-section with diameter d in the measurement volume 104, for example for an oblate spheroid sample object 112 as shown in Figures 7a, 7b.

[0143] In the self-assembled structure, i.e. in close packing of circles, the sample objects 112 form a number of subsets, and all sample objects 112 in a given subset are arranged as a linear chain along a straight line, for example along a horizontal line parallel to the X-axis as in the example of Fig. 7a. Adjacent subsets or linear chains are displaced relative to each other by a distance A1 along the Y-direction, where in the uniform close packing of circles

number

[0144] In other embodiments, the arrangement of the side walls 104-1, 104-2, 104-3, 104-4 may be different and / or the boundary structure of the sensor chip 704 may comprise other elements, such as guiding walls and / or hydrophilic and / or hydrophobic coatings in addition to or instead of the side walls 104-1, 104-2, 104-3, 104-4, as described above for example the sensor chips 200, 300 and 310. The respective boundary structures of the sensor chip 704 are arranged such that when a sample object 112 having a circular cross section with a diameter d is arranged in the measurement volume 104 with the sample object 112 covering the entire first wall 104-A of the measurement volume 104, the sample object 112 is arranged in a self-assembled structure in which a plurality of subsets of the sample object 112 are arranged along respective ones of a plurality of straight lines, for example in a rectangular grid with spacings a1 and a2 as in the example of Figs. 3a and 3b.

[0145] The sensing device 700 further comprises an illumination system 706 for illuminating the sensing elements 115A in the sensing layer 102C. The illumination system 706 is configured to split an incident light beam 708, which may be generated by an external light source, such as a laser (not shown), into a number of illumination light beams 710, which may also be referred to as illumination beams in the following. To this end, the illumination system 706 comprises a number of beam splitters 712 and micromirrors 714 along the optical path of the incident light beam 708. Each of the beam splitters 712 is configured to split a portion of the incident light beam 708 to generate a respective one of the illumination beams 710. The beam splitters 712 may be, for example, polarizing or non-polarizing beam splitters and are preferably configured such that the incident light beam 708 is split into equal portions, i.e. each of the illumination beams 710 has the same optical power. The micromirror 714 is configured to reflect the remaining portion of the incident light beam 708 after passing through the beam splitter 710 to generate another illumination beam 710. The beam splitter 712 and the micromirror 714 can be disposed, for example, on a frame of the mount 702 and can be adjustable, for example tiltable around one or two axes, to align the respective illumination beams 710.

[0146] The illumination system 706 is configured to provide a plurality of illumination beams 710, each of which propagates through the substrate 102 of the sensor chip 704 along an optical path aligned with a respective one of the subsets of sample objects 112, i.e. aligned with a respective line along which the subset of sample objects 112 is disposed. Thereby, the sensing elements 115 adjacent to the respective subset of sample objects 112 in the self-assembled structure can be illuminated by the illumination beam 710. An illumination beam or optical path is said to be aligned with a respective line if the respective optical path extends in a plane that includes the line, i.e. such that the optical path overlaps with the line when viewed along a direction in a plane perpendicular to the line. In some embodiments, the optical paths may extend parallel to or at a small angle to a straight line, e.g., parallel to or at a small angle to the sensing layer 102C and / or bottom wall 104-A of the measurement volume 104, while in other embodiments, the optical paths may form, e.g., a zigzag pattern in the respective planes, e.g., as will be described in more detail below with reference to FIG. 7b.

[0147] In the example of Fig. 7a, the illumination beams 710 are parallel to each other and propagate along the X direction. The illumination beams 710 may propagate, for example, parallel to the bottom wall 104-A of the measurement volume 104 or at a small angle to the bottom wall 104-A, for example, at an angle of less than 10°, in some cases less than 5°, in one example less than 2°, as shown in Fig. 9. The spacing A1 between adjacent illumination beams 710 corresponds to the distance between adjacent linear chains of sample objects 112 in the self-assembled structure, i.e., for close packing of equal circles or spheres,

number

[0148] In some embodiments, the illumination system 706 may comprise one or more diffractive optical elements (not shown) instead of or in addition to the beam splitter 712 and the micromirror 714. Each of the diffractive optical elements may be configured to split an incident beam of light, such as the incident light beam 708, into two or more beams, such as the illumination light beam 710, by diffraction. Each of the diffractive optical elements may be configured, for example, to imprint a phase pattern and / or an intensity pattern onto the incident beam, where interference between different portions of the incident beam causes the incident beam to be split into two or more beams. Each of the diffractive optical elements may comprise, for example, a phase mask and / or a diffraction grating. The illumination system 706 may further comprise one or more focusing elements, such as one or more lenses, which may be configured, for example, to refract and / or deflect the two or more beams generated by the diffractive optical element, some or all of which may propagate at an angle relative to the incident beam, for example to form a pattern of parallel beams similar to that shown in FIG. 7a. To this end, a diffractive optical element may for example be arranged in the focal plane of the respective focusing element.

[0149] In some embodiments, the illumination system 706 may also include one or more light sources, such as lasers (not shown), for example, to generate one or more incident light beams and / or to generate one or more illumination beams 710. In some examples, the illumination system 706 may include a respective light source for each of the illumination beams 710 or for each of multiple subsets of the illumination beams 710.

[0150] In the example of Fig. 7b, the illumination system 706 further comprises optical coatings 716, 718 disposed on the bottom wall 104-A of the measurement volume 104 and on the bottom surface of the substrate 102, respectively. Each of the optical coatings 716, 718 is a reflective coating configured to reflect the illumination beam 710. Preferably, the optical coating 716 on the bottom wall 104-A adjacent to the sensing layer 102C is a broadband reflective coating configured to reflect light at both the absorption wavelengths of the sensing elements 115A, e.g. the wavelength of the illumination beam 710, and the emission wavelengths of the sensing elements 115A, which may correspond to the wavelengths of the sensor signals of the sensing elements 115A, for example. The optical coating 718 on the bottom surface of the substrate 102 may be a dichroic reflective coating configured to reflect light at the absorption wavelengths of the sensing elements 115A and transmit light at the emission wavelengths of the sensing elements 115A, e.g. reflecting the illumination beam 710 while transmitting the sensor signal. The sensor signal may be imaged, for example, through the back surface of the sensor chip 704 onto a light-sensitive detector, such as the measurement device 408 as shown in Figure 4. In some embodiments, the illumination system 706 may not include one or both of the optical coatings 716, 718, but instead the illumination beam 710 may be reflected from the respective surfaces by total internal reflection.

[0151] The illumination system 706 is configured to couple the illumination beam 710 to the sensor chip 704, for example through an inclined incidence facet 720 on a side of the substrate 102, at an incidence angle α with respect to the bottom wall 104-A and / or the bottom surface of the substrate 102. At the substrate 102, each of the illumination light beams 710 can be reflected in turn from the optical coatings 716, 718 and thus propagate through the substrate 102 along a zigzag optical path in a plane parallel to the XZ plane of FIG. 7b. The plane in which the zigzag optical path extends also includes a straight line on which the respective subsets of the sample object 112 are located. The optical coatings 716, 718 are located on both sides of the sensing layer 102C, i.e., above and below the sensing layer 102C, respectively, so that the optical path of each illumination light beam 710 intersects the sensing layer 102C in turn in the sensing region 114A. The sensing region 114A may be, for example, a portion of the sensing layer 102C through which the respective illumination light beam 710 passes, i.e., a portion of the sensing layer 102C through which the sensing elements 115A are illuminated by the respective illumination beam 710. The sensing elements 115A outside the sensing region 114A may not be illuminated by the illumination beam 710. In other words, the illumination beam 710 may generate an "illumination-induced" sensing region 114A in the homogenous sensing layer 102C.

[0152] The illumination system 706 is configured to couple the illumination beam 710 to the sensor chip 704, so that each of the sensing areas 114A is adjacent to a respective one of the sample objects 112 in the self-assembled structure. In this way, the sensing elements 115A in the sensing areas 114A can be selectively addressed with the illumination beam 710, for example, to activate and / or read out the respective sensing elements 115A, thereby creating an "illumination-induced" array of spatially separated sensors adapted to the self-assembled structure of the sample object 112 in the measurement volume 102. This can be achieved, for example, by correspondingly selecting the incidence angle α and the incidence point on the incidence facet 720, for example by correspondingly adjusting the respective beam splitter 712 or micromirror 714. The reflection points of the illumination beam on the optical coating 716, and thus the sensing areas 114A, can be separated, for example, by a distance a2 equal to the diameter d of the sample object 112. The reflecting point, and therefore the sensing area 114A, may be aligned with the centre of a respective one of the sample objects 112 within the self-assembled structure, as shown in Figure 7b.

[0153] In other embodiments, the illumination beams 710 may propagate through the sensing layer 102C parallel to the bottom wall 104-A of the measurement volume 104 or at a small angle, for example less than 5°, in one example less than 2°. Each of the illumination beams 710 may be reflected once along the X direction from the bottom wall 104-A, for example at the coating 716 or by total internal reflection, for example at the center of the bottom wall 104-A. Thus, each of the illumination beams 710 may illuminate, for example, a strip-like portion 710A of the sensing layer 102C under a respective subset of the sample objects 112, for example as described above with reference to FIG. 7a. In such a case, the subset of sensing elements 115A associated with a given sample object 112 may be selected as part of the data processing of the measured sensor signals, for example as described in detail below with respect to the method 800 of FIG. 8. This may involve, for example, defining a "virtual" sensing area 114A within the strip-like portion 710A, which may correspond to a region of interest 710B in a spatially resolved image of a sensing element 115A in the sensing layer 102C.

[0154] In some embodiments, the sensing device 700 may further comprise a measurement device (not shown) for reading out the sensor signal from the sensing element 115A, such as the measurement device 408 of the measurement system 400 of FIG. 4. The measurement device may in particular be a light-sensitive detector configured to record a spatially resolved image of the optical sensor signal of the sensing element, for example a camera chip with a plurality of light-sensitive pixels, such as a CCD or CMOS chip. The sensing device 700 may further comprise a controller (not shown) for selecting a region of interest 710B in the spatially resolved image, for example as detailed below for the method 800 of FIG. 8. The controller may be configured to perform some or all of the steps of the method for parallel probing of multiple samples according to any one of the embodiments described herein, for example the method 500 and / or the method 800. In some embodiments, the sensing device 700 or parts thereof, in particular the mount 702 and / or the illumination system 706, may be provided as an integrated system together with a measurement system according to the invention, such as the measurement system 400.

[0155] FIG. 8 shows a flow diagram of a method 800 for parallel probing of multiple samples according to an exemplary embodiment of the present invention. The method 800 can be implemented, for example, using one of the sensor chips 100, 200, 300, 310, 404, 704, using the measurement system 400, and / or using the sensing device 700. In the following, the method 800 is described using the sensing device 700 and the system 400 as non-limiting examples for illustrative purposes. The method 800 is not limited to the order of execution shown by the flow diagram of FIG. 8. As long as it is technically feasible, the method 800 may be performed in any order, and its steps may be performed at least partially simultaneously, for example, some or all of the steps 804-810 described below.

[0156] The method 800 includes, in step 802, providing a sensor chip having a sensing layer disposed in or on a substrate and a measurement volume adjacent to the sensing layer, for example similar to step 502 of the method 500, the sensing layer comprising a plurality of sensing elements. For example, a sensor chip, such as the sensor chip 704 of the sensing device 700, can be provided that includes a plurality of optically addressable sensing elements 115A, in particular nitrogen vacancy centers, in the sensing layer 102C below the measurement volume 104. The sensor chip 704 may be mounted, for example, in the mount 702 of the sensing device 700 or in the mount 402 of the measurement system 400. This may include aligning the optical path of the illumination beam 710 provided by the illumination system 706 with respect to the sensor chip 704, for example by adjusting the beam splitter 712 and the micromirror 714, or vice versa.

[0157] In step 804, a carrier fluid containing a plurality of sample objects 112 is provided to the measurement volume 104 of the sensor chip 704, e.g., as described above for step 504 of method 500. In step 806, the plurality of sample objects 112 in the measurement volume 104 are controlled such that the sample objects 112 form a self-assembled structure, e.g., as described above for step 506 of method 500. The self-assembled structure may be, for example, a close packing of equal circles or spheres as shown in Figure 7a, where each of the sample objects 112 is positioned at a predetermined location within the measurement volume 104.

[0158] The method 800 further includes selecting, at step 808, a respective subset of the sensing elements 115A on the sensor chip 704 for each sample 112A on which measurements are performed at step 810, e.g., for each of the samples 112A. The measurements on the samples 112A at step 810 may be performed using only the respective subset of sensing elements 115A, e.g., by selectively determining sensor signals from these sensing elements 115A. The subset of sensing elements 115A may be selected prior to forming the self-assembled structure of the sample object 112 at step 808, e.g., because the position of the sample object 112 within the self-assembled structure is known a priori, or may be selected after forming the self-assembled structure based on the position of the sample object 112 within the self-assembled structure experimentally determined, e.g., using a camera. In some embodiments, the subset of sensing elements 115A may also be selected after performing measurements at step 810, e.g., as part of data processing of the measured sensor signals.

[0159] To select a subset of the sensing elements 115A, a region of interest 710B may be selected for each of the sample objects 112 in the self-assembled structure, for example, to perform a selective readout of the sensing elements associated with the region of interest. The region of interest 710B may be defined, for example, as part of a spatially resolved image of the sensor chip 704, which may in particular be a microscope image of the sensing layer 102C that records the intensity of light emitted by the sensing elements 115A as a function of the position of the sensing layer 102C in the XY plane of FIG. 7a. The region of interest 710B in the spatially resolved image may, for example, correspond to a sensing area 114A in the sensing layer 102C adjacent to the respective sample object 112 in the self-assembled structure, or may correspond to a part of this sensing area 114A. The sensing area 114A may be, for example, a spatially separated sensing area or sensor defined by a non-uniform distribution of sensing elements 115A in the sensing layer 102C, as in the example of Figure 1a, an illumination-induced sensing area defined by the intersection of an illumination beam with the sensing layer 102C, as in the example of Figure 7b, or a "virtual" sensing area that may be selected, for example, from an illuminated strip-shaped portion 710A of the sensing layer 102C or from a uniformly illuminated sensing layer 102, as in the example of Figure 7a.

[0160] In addition to or instead of selecting the region of interest 710B, a subset of the sensing elements 115A may be selected by selective illumination of the sensing layer 102C, for example to selectively activate and / or read out the sensing elements 115A by patterned illumination. This may include selectively illuminating the sensing layer 102C with the illumination beam 710, as detailed above with reference to Figs. 7a, 7b, among others. For example, only the sensing elements 115A in the strip-shaped portion 710A in Fig. 7a or only the sensing elements 115A in the sensing area 114A in Fig. 7a or 7b may be illuminated by the illumination beam 710 and thus generate a sensor signal for probing the sample 112A.

[0161] In step 810, measurements are performed on one or more of the samples 112A while the sample object 112 is placed in the self-assembled structure in the measurement volume 104, the measurements being performed using the subset of sensing elements 115A selected in step 808. The measurements can be performed, for example, by illuminating the sensing elements 115A in the sensing layer 102C with the illumination beam 710 and recording the intensity of light emitted by the sensing elements 115A as a sensor signal using a light-sensitive detector such as the measurement device 408. The sensor signal is selectively determined using only the sensing elements 115A in the selected subset, for example, by selectively illuminating the sensing elements 115A with the illumination beam 710 and further discarding the sensor signals outside the region of interest 710B, i.e. the sensor signals resulting from the sensing elements 115A outside the sensing region 114A.

[0162] Thereby, the method 800 enables parallel probing of multiple samples using a sensor chip that is reusable, can be easily manufactured, and is simple to handle. Only a few boundary structures are used to position the sample objects in a well-defined and reproducible self-assembled structure, so that no microscopic structures such as microfluidic sample wells are required, which complicate the manufacturing process on the sensor chip as well as the sample preparation, and are nearly impossible to clean. Furthermore, selective probing of each sample can also be performed using a homogenous sensing layer with a uniform distribution of sensing elements, which further simplifies the manufacturing of the sensor chip.

[0163] 9 shows a schematic diagram (not to scale) in side view of a sensor chip 900 of a sensing device 700 according to another exemplary embodiment of the present invention. The sensor chip 900 is similar to the sensor chip 704 of FIG. 7b, and corresponding elements are labeled using the same reference numerals as in FIG. 7, and descriptions thereof are omitted for brevity.

[0164] In the example of FIG. 9, the illumination beams 710 are coupled into the sensor chip 900 through the side of the substrate 102, for example using the illumination system 706 of the sensing device 700, such that the illumination beams 710 propagate through the sensing layer 102C at an angle β with respect to the bottom wall 104-A of the measurement volume 104. The angle β may be selected, for example, such that the optical path of the illumination beams 710 remains within the sensing layer 102C throughout the substrate 102 and / or such that the illumination beams 710 may be reflected from the bottom wall 104-A by total internal reflection. Preferably, each illumination beam 710 is reflected once from the bottom wall 104-A, for example by total internal reflection, at the center of the measurement volume 104, for example along the X-axis as shown in FIG. 9. The angle β may be, for example, between 0° and 5°, for example between 0.5° and 2°. Thus, each of the illumination beams 710 may illuminate a strip-shaped portion of the sensing layer 102C beneath a respective subset of the sample objects 112, for example as shown in FIG. 7a.

[0165] Within the sensing layer 102C, sensing regions 114A associated with each sample object 112 within the self-assembled structure in the measurement volume 104 can be selected or defined, for example, by selectively determining a sensor signal from a sensing element 115A within the corresponding region, for example by detecting only light emitted by NV centers within a particular portion of the sensing layer 102C.

[0166] In some embodiments, the sensor chip 900 may comprise a number of microlenses 902, particularly solid immersion lenses as in the example of FIG. 9, which may be arranged, for example, on or adjacent to the bottom surface of the substrate 102 as shown in FIG. 9. In other examples, the microlenses 902 may be provided, for example, as part of the sensing device 700 or the measurement system 400. Each microlens 902 may define a corresponding sensing area 114A in the sensing layer 102C, which may comprise, for example, all sensing elements 115A within the field of view of the respective microlens 902. Each microlens 902 may be configured to collect light emitted by the sensing elements 115A in the corresponding sensing area 114A, thereby allowing selective determination of the sensor signal from the sensing elements 115A in the corresponding sensing area 114A. The microlenses 902 may be arranged in a one-dimensional or preferably two-dimensional array that defines a corresponding array of sensing areas 114A in the sensing layer 102C, as shown, for example, in FIG. 7a.

[0167] Additionally or alternatively, the sensing area 114A may be defined by, for example, a pinhole array 904, which may be provided, for example, as part of the sensing device 700 or the measurement system 400. The pinhole array 904 comprises a plurality of pinholes or openings, each of which is associated with a respective sensing area 114A in the sensing layer 102C. Each pinhole is configured to transmit light originating from the respective sensing area 114A, while light originating outside the respective sensing area 114A, in particular from adjacent parts of the sensing layer 102C, is blocked by the pinhole array 904. This also allows for selectively determining the sensor signal from the sensing element 115A in the corresponding sensing area 114A. The pinhole array 904 may be arranged, for example, in an image plane of the microlens 902 as shown in FIG. 9 or in an image plane of an imaging system (not shown) of the measurement system 400. In other embodiments, the pinhole array 904 may be arranged, for example, on or adjacent to a bottom surface of the substrate 102 or on or adjacent to a measurement device 408 of the measurement system 400, which may be, for example, a camera with a CCD or CMOS chip. The pinholes of the pinhole array 904 may be arranged in a one-dimensional, or preferably a two-dimensional, array that defines a corresponding array of sensing areas 114A in the sensing layer 102C, as shown, for example, in FIG.

[0168] In some embodiments, the sensing area 114A may also be defined by the measurement device 408 of the measurement system 400, for example, in addition to or instead of the microlenses 902 and / or the pinhole array 904. The measurement device 408 may, for example, comprise a plurality of spatially separated measurement elements 410, each of which is associated with a respective one of the sensing areas 114A, as shown in FIG. 9. The measurement elements 410 may be light-sensitive elements, such as, for example, photodiodes, CCD or CMOS chips, or spatially separated pixels of a CCD or CMOS chip. The microlenses 902 or an imaging system (not shown) of the measurement system 400 may, for example, be configured to image the light originating from the sensing area 114A onto the respective light-sensitive elements 410, which may be configured to determine the intensity of the light. The sensing area 114A may thus be defined as the area in the sensing layer 102C that is imaged onto the respective light-sensitive elements 410. The spacing a2 between adjacent sensing areas 114A can correspond to the spacing between adjacent light-sensitive elements 410 divided by the imaging magnification, and the size of the sensing areas 114A can correspond to the size of the light-sensitive elements 410 divided by the imaging magnification. In another example, the light-sensitive elements 410 may be arranged in close proximity to the sensor chip 900, for example on or adjacent to the bottom surface of the substrate, which may allow light to be collected from the individual sensing areas 114A without the need for an imaging system. The light-sensitive elements 410 may be arranged in a one-dimensional or preferably two-dimensional array that defines a corresponding array of sensing areas 114A in the sensing layer 102C, for example as shown in FIG. 7a. By using a measurement device 408 with spatially separated light-sensitive elements 410 associated with each sensing area 114A, the number of light-sensitive elements 410 can be reduced, for example compared to a continuous camera chip with multiple pixels covering the same area. This can reduce the amount of data that must be processed and can speed up the readout of the measurement device 408.

[0169] The sensor chip 900, the pinhole array 904, and / or the measurement device 408 may be used with the sensing device 700 of FIG. 7a, for example, to select the sensing area 114A from the strip-like portion 710A illuminated by the illumination beam 710. In other examples, different sensor chips and / or different types of illumination may be used, and the sensing area 114A may be similarly defined, for example, in a uniformly illuminated sensing layer, in a selectively illuminated sensing layer as in FIG. 7b, and / or in a sensing layer with spatially separated sensing areas as in FIG. 1b. In other words, individually addressable and distinguishable sensing areas may be obtained by one or more of a spatially non-uniform or selective distribution of sensing elements in the sensing layer, a spatially non-uniform or selective illumination of the sensing layer, and a spatially non-uniform or selective detection of the sensor signal from the sensing layer. Thereby, the sample object 112 in the self-assembled structure may be individually probed using the sensing elements of the respective sensing areas.

[0170] The embodiments of the present invention disclosed herein merely constitute specific examples for illustrative purposes. The present invention can be implemented in various ways and with many modifications without changing the basic characteristics underlying it. The present invention is therefore defined solely by the claims. [Explanation of symbols]

[0171] 100 sensor chips 102 Substrate 102A Lower Board 102B Top Board / Cover 104 Measuring Volume 104A Bottom wall 104B Upper wall 104-1,104-2,104-3,104-4 Side wall 104a Proximal part 104b Central part 104c distal part 106, 106A, 106B input ports 108, 108A, 108B output ports 110 Droplet generator 112 Sample Object 112A Sample 112B Shell layer 114A, 114B Sensor / detection area 115A,115B sensing element 116 Unit Cell 200 Sensor Chips 202 Inlet channel 204 Outlet Channel 206 Valve 300 Sensor Chips 302 Guidance wall 310 Sensor Chip 312 Coating 400 Measurement System 402 Mount 404 Sensor Chip 406 Microfluidic Unit 408 Measuring Devices 410 Measurement elements 412 Controller 414 Light source 416 Camera 418 Sorting Unit 500 Method for Probing Multiple Samples in Parallel 502 A process for providing a sensor chip 504 Providing a carrier fluid containing a plurality of sample objects. 506 A process for forming a self-organized structure of a sample object 508 performing measurements on one or more samples 700 Sensing Devices 702 Mount 704 Sensor Chip 706 Lighting System 708 Incident light beam 710 Illumination Light Beam 710A Strip-shaped part 710B Region of Interest 712 Beam splitter 714 Micromirror 716 Broadband Reflective Coating 718 Dichroic Reflective Coating 720 entrance facet 800 METHOD FOR PROBING MULTIPLE SAMPLES IN PARALLEL 802 A process for providing a sensor chip Providing a carrier fluid containing a plurality of sample objects. 806 A process for forming a self-organized structure of a sample object 808 Selecting a subset of sensing elements within the sensing region 810 performing measurements on one or more samples using the selected subset. 900 Sensor Chip 902 Micro Lens 904 Pinhole Array a1, a2 sensor array spacing D, D1, D2 side wall distance d diameter of sample object A1 Distance between the optical paths of the illumination light beams α Incidence angle of the illumination light beam

Claims

1. 1. A method (500, 800) for parallel probing of a plurality of samples (112A), the method (500, 800) comprising: A sensor chip (100, 200, 300, 310, 404, 704, 900) is provided, the sensor chip (100, 200, 300, 310, 404, 704, 900) comprising a sensing layer (102C) disposed in or on a substrate (102) and a measurement volume (104) adjacent to the sensing layer (102C), the sensing layer (102C) comprising a plurality of sensing elements (115A, 115B), each of the plurality of sensing elements configured to generate a sensor signal characterizing a physical observable in a vicinity of the respective sensing element (115A, 115B); providing a carrier fluid containing a plurality of sample objects (112) into the measurement volume (104), each of the sample objects (112) comprising or forming a respective sample (112A); controlling a plurality of sample objects (112) within the measurement volume (104) such that the sample objects (112) form a self-assembled structure within the measurement volume (104), the self-assembled structure being a structure in which an arrangement of the sample objects (112) is at least partially defined by interactions between the sample objects (112) themselves; performing measurements on one or more of the samples (112A) while the sample objects (112) are disposed within the self-assembled structure, the measurements on the samples (112A) being performed using one or more sensing elements (115A, 115B) disposed adjacent to each of the sample objects (112) within the self-assembled structure; A method (500, 800) comprising:

2. The method (500, 800) of claim 1, wherein performing the measurement on the one or more samples (112A) comprises: selecting a subset of the sensing elements (115A) for each of the one or more samples (112A), wherein the sensing elements (115A) in the subset are positioned within a sensing region (114A) adjacent to each of the sample objects (112) in the self-assembled structure; and selectively determining a sensor signal from the sensing elements (115A) in the sensing region (114A).

3. The method (500, 800) of claim 2, wherein selecting the subset of sensing elements (115A) and selectively determining the sensor signal from the sensing elements (115A) in the sensing area (114A) comprises selectively activating the sensing elements (115A) in the sensing area (114A) and / or selectively reading out the sensing elements (115A) in the sensing area (114A).

4. the sensing elements (115B) in the sensing layer (102C) form a sensor array of spatially separated sensors (114B), each of the sensors (114B) comprising one or more sensing elements (115B); Each of the sample objects (112) is disposed adjacent to each of the sensors (114B) within the self-assembled structure; The method (500, 800) according to any one of claims 1 to 3, wherein measurements on a sample (112A) are performed using the respective sensor (114B).

5. The spacing (a 1 , a 2 ) is the spacing (a 1 , a 2 ) is selected to correspond to a physical dimension (d) of said sample object (112), or The physical dimension (d) of the sample object (112) is determined by the distance (a) between the sensor arrays. 1 , a 2 5. The method of claim 4, wherein the first and second inputs are selected to correspond to the first and second inputs.

6. The method (500, 800) according to any one of claims 1 to 3, wherein the sample object (112) is a microdroplet dispersed in the carrier fluid.

7. 7. The method (500, 800) of claim 6, wherein the carrier fluid and the microdroplets (112) form an emulsion and / or the carrier fluid and / or the microdroplets (112) each contain a surfactant that forms a shell layer (112B) around the respective sample (112A).

8. the sensor chip (100, 200, 300, 310, 404, 704, 900) comprises a boundary or guidance structure (104-1, 104-2, 104-3, 104-4, 302, 312) configured to limit or guide the movement of the sample object (112) within the measurement volume (104); The method (500, 800) according to any one of claims 1 to 3, wherein the self-assembled structure is formed by interactions between the sample objects (112) and the boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) and by surface-surface interactions between the sample objects (112).

9. 9. The method (500, 800) of claim 8, wherein in the self-assembled structure, the interactions between the sample objects (112) and the boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) and the surface-surface interactions between the sample objects (112) prevent at least 90%, preferably at least 95%, of the sample objects (112) from moving along two or more orthogonal directions.

10. 4. The method (500, 800) of any one of claims 1 to 3, wherein the sample object (112) has a circular cross-section and the self-assembled structure is a close packing of equal circles.

11. The method (500, 800) of any one of claims 1 to 3, wherein the carrier fluid containing the sample objects (112) is supplied through a microfluidic inlet channel (202) fluidly connected to the measurement volume (104), and controlling the plurality of sample objects (112) in the measurement volume (104) comprises maintaining a flow of the carrier fluid containing the sample objects (112) through the inlet channel (202) until the self-assembled structure is formed.

12. The method (500, 800) of any one of claims 1 to 3, further comprising tracking the movement of a sample object (112) on the sensor chip (100, 200, 300, 310, 404) before and / or after performing a measurement on the respective sample (112A).

13. The sensing element (115A) is an optically addressable solid-state spin system, in particular a nitrogen vacancy centre in diamond, and performing a measurement on the sample (112A) comprises: illuminating a solid-state spin system (115A) disposed within a sensing region (114A) adjacent to each of the sample objects (112) in the self-assembled structure with light to optically excite the solid-state spin system (115A) within the sensing region (114A); 4. The method (500, 800) of any one of claims 1 to 3, comprising detecting an optical signal emitted by the solid-state spin system (115A) within the sensing region (114A).

14. A sensor chip (100, 200, 300, 310, 404) for probing multiple samples (112A) in parallel using the method (500, 800) of claim 1, said sensor chip (100, 200, 300, 310, 404) comprising: a measurement volume (104) configured to receive a carrier fluid containing a plurality of sample objects (112); An array of sensors (114B) disposed within or adjacent to a first wall (104-A) of the measurement volume (104), the sensor array having a first spacing a 1 an array of sensors (114B), each of the sensors (114B) comprising one or more sensing elements (115B), each of the sensing elements configured to generate a sensor signal characterizing a physical observable in a vicinity of the respective sensing element (115B); two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) configured to limit or guide the movement of the sample object (112) within the measurement volume (104); The two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) are spaced apart from each other by the first interval a 1 a close-packing of solid objects having a circular cross-section with a diameter d equal to d is disposed within the measurement volume (104), and the two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) are arranged to confine the solid objects such that, when the close-packing of the solid objects covers the entire first wall (104-A) of the measurement volume (104), each solid object is aligned with each of the sensors (114B).

15. The boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) are side walls (104-1, 104-2, 104-3, 104-4) of the measurement volume (104), the side walls (104-1, 104-2, 104-3, 104-4) extending at an angle to the first wall (104-A); a guide wall (302) protruding from the first wall (104-A) of the measurement volume (104) and / or from a second wall (104-B) of the measurement volume (104) opposite the first wall (104-A); and / or 15. The sensor chip (100, 200, 300, 310, 404) of claim 14, comprising one or more of a hydrophilic and / or hydrophobic coating (312) on the first and / or second walls (104-A, 104-B) of the measurement volume (104).

16. A sensor chip (100, 200, 300, 310, 404) according to claim 14 or claim 15, wherein the sensor array corresponds to a tiling of identical unit cells, with each sensor (114B) associated with a respective unit cell, and segments of the boundary or guiding structure (104-1, 104-2, 104-3, 104-4, 302, 312) are aligned with edges of unit cells along a circumference of the sensor array.

17. Each of the outermost sensors of the sensor array is spaced apart from at least one of the boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) by a first distance a. 1 16. The sensor chip (100, 200, 300, 310, 404) according to claim 14 or 15, arranged at a distance corresponding to half of the

18. 16. The sensor chip (100, 200, 300, 310, 404) according to claim 14 or claim 15, wherein the two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) are arranged such that, in the close packing of the solid objects, contact between the solid objects and between the solid objects and the boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) prevents at least 90%, preferably at least 95%, of the solid objects from moving in a plane parallel to the first wall.

19. The two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) are [0010] 16. The sensor chip (100, 200, 300, 310, 404) according to claim 14 or claim 15, comprising two opposing boundary or guiding structures (104-1, 104-2, 104-3, 104-4) separated by a distance D where M and N are positive integers, in particular M and / or N are positive integers greater than 1.

20. The sensor array has a first spacing a 1 and a second interval a in the second direction. 2 16. The sensor chip (200, 300, 310, 404) according to claim 14 or 15, which is a two-dimensional periodic array having

21. The sensors (114B) in the array are spaced apart by a h and the boundary or guiding structure (104-1, 104-2, 104-3, 104-4, 302, 312) comprises a first pair of opposing side walls (104-1, 104-2) of the measurement volume and a second pair of opposing side walls (104-3, 104-4) of the measurement volume (104). The first pair of side walls (104-1, 104-2) are spaced apart by a first distance [0025] Separated by N 1 is a positive integer greater than 1, The second pair of side walls (104-3, 104-4) are D 2 =(N 2 +1)・a h or [0030] The second distance D 2 Separated by N 2 The sensor chip (200, 404) of claim 20, wherein is a positive integer greater than 1.

22. 16. The sensor chip (100, 200, 300, 310) according to claim 14 or 15, further comprising a droplet generator (110) configured to generate monodisperse microdroplets of sample fluid in the carrier fluid.

23. The sensor chip (200) of claim 14 or claim 15, comprising a microfluidic inlet channel (202) and a microfluidic outlet channel (204), the inlet channel and the outlet channel (202, 204) being fluidly connected to the measurement volume (104), and the sensor chip (200) further comprising means (206) for selectively preventing the sample object (112) from exiting the measurement volume (104) through the outlet channel (204).

24. A sensor chip (100, 200, 300, 310, 404) according to claim 14 or claim 15, wherein the sensing element (115B) is an optically addressable solid-state spin system, in particular a nitrogen vacancy centre in diamond.

25. The distance between each of the sensors (114B) and the surface of the first wall (104-A) exposed to the measurement volume (104) is equal to the first spacing a 1 and preferably less than twice the first interval a 1 The sensor chip (100, 200, 300, 310, 404) according to claim 14 or claim 15,

26. A sensing device (700) for parallel probing of multiple samples (112A) using the method (500, 800) of claim 1, said sensing device (700) comprising: a sensor chip (200, 300, 310, 404, 704, 900) comprising a substrate (102) and a measurement volume (104) configured to receive a carrier fluid containing a plurality of sample objects (112), the substrate (102) comprising a plurality of optically addressable sensing elements (115A) arranged in a sensing layer (102C) in or below a first wall (104-A) of the measurement volume (104), each of the sensing elements (115A) configured to generate a sensor signal characterizing a physical observable in the vicinity of the respective sensing element (115A); an illumination system (706) for illuminating the sensing element (115A); the sensor chip (200, 300, 310, 404, 704, 900) further comprises two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) configured to restrict or guide a movement of the sample object (112) within the measurement volume (104), the two or more boundary or guiding structures (104-1, 104-2, 104-3, 104-4, 302, 312) being arranged such that when a solid object having a circular cross-section with a diameter d is placed within the measurement volume (104), the solid object covers the entire first wall (104-A) of the measurement volume (104), the solid objects being arranged in a self-assembled structure in which a plurality of subsets of the solid objects are each arranged along a respective one of a plurality of straight lines, A sensing device (700), wherein the illumination system (706) is configured to provide a plurality of illumination light beams (710), each of which propagates through the substrate (102) along an optical path aligned with a respective one of the plurality of straight lines to illuminate a sensing element (115A) adjacent to the solid object of the respective subset within the self-assembled structure.

27. 27. The sensing device (700) of claim 26, wherein the illumination system (706) is configured to split an incident light beam (708) into the plurality of illumination light beams (710).

28. The optical paths of the illumination light beams (710) are parallel to each other and have a spacing A 1 Separated by [0045] 28. The sensing device (700) of claim 26 or claim 27,

29. A sensing device (700) as described in claim 26 or claim 27, wherein one or more of the optical paths of the illumination light beam (710) extend through the sensing layer (102C) at an angle of less than 10°, preferably less than 5°, relative to the first wall (104-A) of the measurement volume (104).

30. 28. The sensing device (700) of claim 26 or claim 27, wherein, for one or more of the optical paths of the illumination light beam (710), light propagating along the respective optical paths is sequentially reflected from a first surface (104-A, 716) above the sensing layer (102C) and a second surface (718) below the sensing layer (102C) such that the optical path intersects the sensing layer (102C) at a sensing region (114A), each of the sensing regions (114A) adjacent a respective one of the solid objects within the self-assembled structure.

31. 28. The sensing device (700) of claim 26 or claim 27, wherein the sensing elements (115A) are uniformly distributed throughout the sensing layer (102C).

32. Each of the sensing elements (115A) is configured to generate a photosensor signal, and the sensing device (700) comprises: a photosensitive detector (408) configured to record a spatially resolved image of the sensor signal of the sensing element (115A); 28. The sensing device (700) of claim 26 or claim 27, further comprising: a controller (412) configured to select a region of interest (710B) in the spatially resolved image for each of at least a portion of the solid objects in the self-assembled structure, the region of interest (710B) including sensor signals arising from sensing regions (114A) adjacent to each of the solid objects in the self-assembled structure.

33. 28. The sensing device (700) of claim 26 or claim 27, wherein the sensing element (115A) is an optically addressable solid-state spin system, in particular a nitrogen vacancy centre in diamond.

34. 28. The sensing device (700) of claim 26 or claim 27, further comprising a mount (706) configured to receive the sensor chip (200, 300, 310, 404, 704, 900), and the illumination system (706) is disposed on the mount (706).

35. A measurement system (400) for parallel probing of multiple samples (112A) using the method (500, 800) of claim 1, said measurement system (400) comprising: a mount (402, 702) configured to receive a sensor chip (100, 200, 300, 310, 404, 704, 900), the sensor chip (100, 200, 300, 310, 404, 704, 900) comprising a sensing layer (102C) disposed in or on a substrate (102) and a measurement volume (104) adjacent to the sensing layer (102C), the sensing layer (102C) comprising a plurality of sensing elements (115A, 115B), each of the plurality of sensing elements configured to generate a sensor signal characterizing a physical observable in a vicinity of a respective sensing element (115A, 115B); a microfluidic unit (406) configured to supply a carrier fluid containing a plurality of sample objects (112) to the measurement volume (104) when the sensor chip (100, 200, 300, 310, 404, 704, 900) is placed in the mount (402, 702); a measuring device (408) configured to read a sensor signal from the sensing element (115A, 115B) when the sensor chip (100, 200, 300, 310, 404, 704, 900) is placed on the mount (402, 702); A controller (412), The controller (412) controlling the microfluidic unit (406) to control a plurality of sample objects (112) in the measurement volume (104) such that the sample objects (112) form a self-assembled structure in the measurement volume (104), the self-assembled structure being a structure in which the arrangement of the sample objects (112) is at least partially determined by interactions between the sample objects (112) themselves; A measurement system (400) configured to control the measurement device (408) to perform measurements on one or more of the samples (112A) while the sample objects (112) are disposed within the self-assembled structure, wherein the measurements on the samples (112A) are performed using one or more sensing elements (115A, 115B) disposed adjacent to each of the sample objects (112) within the self-assembled structure.

36. A measurement system (400) according to claim 35, and A sensor chip (100, 200, 300, 310, 404) according to claim 14, wherein the mount (402) of the measurement system (400) is configured to receive the sensor chip (100, 200, 300, 310, 404), or A set comprising a sensing device (700) as described in claim 26, wherein the mount (402, 702) of the measurement system (400) comprises a sensing device (700) configured to receive the sensor chip (704, 900) of the sensing device (700).

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