OPTICAL SENSORS BASED ON NANO STRUCTURES

Description

OPTICAL SENSORS BASED ON NANO STRUCTURES * * * * * Technical field The present invention relates to an ultrasensitive optical sensor, in single configuration or integrable into a sensor system, coupleable to a light source and a detection device, which is capable to detect the presence and / or concentration of an analyte in a matrix real (such as air, gases, aerosols, aqueous solutions), through the induction of hybrid plasmon resonances caused from the interaction between the incident visible radiation and a surface nanostructured metal based on, for example, pollen. Known art The selective detection of particular analytes in different matrices is a increasing demand in numerous application fields including, for example, the diagnosis of tumor markers, the analysis of various environmental pollutants emerging, bioterrorism or biodefense, pandemic emergencies, the personalized medicine, point-of-care tests for various analyses or pre- analysis. In such applications there is a need to use sensors with very high performances that allow the detection of quantities infinitesimal quantities of analytes (e.g., proteins, ions, complexes, molecules), or of multiple molecules at the same time (in the case of arrays). Among the optical sensors used, the waveguide ones stand out, for example in plastic optical fibers (POF) or in planar waveguide polymeric and inorganic (silica, quartz), to monitor the variation of refractive index of a receptor through the physical effect of resonance surface plasmonic (SPR) or localized (LSPR), or those based on hybrid plasmonic phenomena present in periodic nanostructures made using lithographic techniques (electronic or optical). In order to obtain an improvement of the plasmonic phenomenon and therefore of the performance of the biochemical sensor in terms of sensitivity instrumental and detection limit, it is possible to resort to the use of so-called plasmonic metasurfaces based for example on structures periodic or pseudo-periodic nanocones, nanowires, nanotips, nanostrips, nanopillars, or nanolattices, usually produced with complex manufacturing techniques (e.g., electron lithography) characterised by high costs and long production times. In the field of sensing, optical sensitivity is often defined as the detectable change in the signal (for example the change in the resonance wavelength) relative to a unit variation of the refractive index. Biochemical sensitivity is instead defined as the detectable change in the signal related to a change unit of the concentration of the substance to be measured. Generally in the case of optical biosensors the detection limits related to the specific measure of a given substance are typically of the order nanograms / liter, often obtaining a high selectivity / specificity towards the molecule of interest (target) which is properly function of the receptor used (natural or synthetic). There are application contexts where biochemical sensitivity is required very high, i.e. a detection limit much lower than that of the order of nanograms / liter, almost at the level of a single molecule (range attomolar). As an example, these specifications are required in the measurement of some particular biomarkers, of several emerging pollutants, for the measurement of viruses or bacteria, in the quantitative measurement of certain substances useful in so-called personalized and / or precision medicine, or in tests for rare diseases, for the measurement of explosives and other specifics hazardous substances. As is evident from the analysis of the prior art, the development of optical sensors extremely high sensitivity but at the same time economically accessible and simple feasibility / implementability continues to be a primary needs in the field of sensors. As far as they have been carried out numerous steps forward, the obstacle of obtaining nanostructured systems of easy availability, easy production and easy use has not been still outdated. Added to this is the continuous search for devices sensors that are not only able to detect concentrations -18 particularly small analytical values ​​(range of 10 molar) but which can also perform measurements on a wide variety of analytes, even simultaneously, thanks to an intrinsic instrumental ductility and versatility. Unless otherwise specified, the contents of this section is to be considered as an integral part of the description detailed below. Summary of the invention The first aim of the present invention is the realization of a sensor optical or sensor chip as set forth in claim 1. Other objects of the invention are a sensor system also called apparatus comprising the sensor chip of the invention, and the process for the creation and use of said sensor. Further purposes will be apparent from the detailed description below reported. Brief description of the Figures The invention will be described below in at least one embodiment. preferred for explanatory purposes only and not to limit the scope of the present invention with the aid of the attached figures, of which: • Figure 1a: Natural nanostructure based on sunflower pollen; • Figure 1b: sunflower pollen opening; • Figure 1c: immobilization of pollen (of figure 1b) on a transparent and guiding substrate 1000; • Figure 1d: Coating of immobilized pollen with a layer nanometric metallic; • Figure 1e: Schematic of the optical sensor based on a structure natural periodic or pseudo-periodic; • Figure 2a: image acquired by scanning microscope electronics (SEM) of the surface of the optical sensor based on pseudo-periodic natural nanostructures; • Figure 2b: image acquired by SEM and relating to a detail of the pseudo-periodic nano-tips present on the surface of the sunflower pollen; • Figure 3a: Schematic view of a sensor system according to the present invention; • Figure 3b: Schematic view of an optical multisensor according to the present invention; • Figure 4a: schematic view of a possible configuration experimental sensor system; • Figure 4b: schematic view of a possible configuration experimental sensor system; • Figure 5a: Normalized hybrid plasmon resonance spectra of the ultra-sensitive optical sensor as a function of the wavelength; • Figure 5b: Comparative graph showing the absolute value of the variation of the resonance wavelength towards the index of refraction of the external medium for the optical sensor of the invention and for a standard comparison sensor based on a nanograting produced by electron beam lithography (EBL); • Figure 6: Hybrid plasmon resonance spectra of the optical sensor as a function of wavelength, normalized with the spectrum acquired from the reference chip and acquired at different concentrations of estradiol; • Figure 7: graph of the absolute value of the variation of the wavelength of the hybrid surface plasmon resonance of the optical biosensor as the concentration of a estradiol solution in contact with said biosensor; • Figure 8: Bar graph of biosensor specificity / selectivity ultrasensitive of the invention compared to other analytes / substances such as bovine albumin (BSA) and dihydrotestosterone (DHT), tested in concentration ranges much higher than the specific analyte (estradiol). Definitions • In this document, the terms “about” or “around” as here used when referring to a measurable value such as a quantity, a time duration, and the like, are meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the value specified, where such variations are appropriate to perform the methods described. • In this document, the terms, "includes", "includes", "has", "having", "contains", "containing", "characterized by" or any other variations of these terms, are intended to cover a non-exclusive inclusion, subject to any limitations explicitly indicated. For example, a composition, a mixture, a process or method that includes a list of elements is not necessarily limited to just these elements, but may include other elements not expressly listed or related to such composition, mixture, process or method. • In this document, in all embodiments of the present invention, with “upper face” of the optical sensor of the invention means the face that includes the receptor covalently immobilized on the metal surface, instead, by “bottom face” of the optical sensor we mean the face that includes the surface of the substrate 1000 opposite to that of the direct contact with the first base layer 100, i.e. including the surface lower than 1001. • In this document, the term “intra-pollen period” indicates the distance between two consecutive nanotips of the same size pollen grain, where said nanospikes are nanostructures that They externally cover the surface of the pollen grains. • In this document, the term “inter-pollen period” refers to the distance between two nanotips of two pollen units consecutive immobilized on the surface of the substrate. • In this document, the term “sensor system” refers to means an instrumental configuration for the detection of a analyte comprising at least one sensor chip according to the invention, at least one reference chip, at least one source light and at least one detection device (or detector). • In this document, the terms “sensitive structure 200”, “layer sensitive 200” and “sensitive zone 200” are to be considered synonyms and include periodic or pseudo-periodic nanostructures. • In this document, the term “dielectric” refers to the solution, the mixture or fluid (such as air, gases, aerosols, aqueous solutions,), also referred to as “bulk” or medium, which can optionally contain the analyte to be analyzed, with which they are both the sensor chip and the control chip are in contact or immersed reference; in particular it is the medium placed in contact with the nanofilm metal functionalized with the receptor of the upper face of the sensor chip and with the metal nanofilm of the reference chip. • In this document, the terms “sensor chip”, “sensor”, and “optical sensor” are used synonymously. • In this document, the term “biosensor” is used for indicate the optical sensor of the invention in which the receptor layer 400 comprises a bioreceptor, e.g. an antibody. Detailed description The present invention relates to an optical sensor for the detection and the specific and selective quantification of one or more analytes within a sample under examination. The optical sensor according to the present invention is a device comprising a plurality of superimposed layers, arranged in a manner tidy and functional for the purpose, and which superficially presents a periodic or pseudo-periodic (semi-periodic) nanometric structure. The optical sensor according to the present invention, exposing externally a nanostructured surface, is able to generate surface hybrid plasmon resonances (e.g., due to a combination of SPR and LSPR) induced by appropriate stimulation light, which can be recorded by an appropriate recording device detection. The presence of a specific analyte interacting with dislocated receptors on the upper face of the optical sensor of the invention is able to induce a shift in the resonance wavelength ( ) hybrid plasmonics; this variation can be related to the presence / quantity of the analyte of interest. The periodic or pseudo-periodic nanometric structure that covers superficially the upper face of the optical sensor (or sensor chip) according to the present invention it can be natural or synthetic. In the preferred embodiments of the present invention, used a pseudo-periodic structure of natural origin from from pollen, preferably sunflower pollen. Without having to resort to lithographic techniques or manufacturing processes complex, it is possible to resort to the implementation of natural systems such as pollen inside the optical sensor(s) of the invention. Said pollen, appropriately treated and coated with one or more metallic layers of nanometric thickness, is capable of generating the aforementioned phenomena hybrid plasmonics due to a pseudo-periodic nanometric structure superficial. Referring to the figures, an optical sensor based on a periodic or pseudo-periodic structure such as that of pollen sunflower, to detect the presence and / or concentration of an analyte in a matrix, even gaseous, downstream of a functionalization of the same with a natural or synthetic receptor, preferably specific for the type of analyte sought. In this document, for the sake of simplicity, reference will be made to an illustrated XYZ Cartesian axes system where the longitudinal X axis, the transverse Y-axis and the vertical Z-axis are respectively the axis of longitudinal development, the axis of development in width and the axis of development in height of the optical sensor according to the present invention, as illustrated in figure 1e. Furthermore, the terms “superior”, “inferior” and “lateral” will reference to the relative position with respect to the sensor configurations ultrasensitive optical according to the invention illustrated in figure 1e. As shown in figure 1e, the ultra-sensitive optical sensor according to the invention comprises in the lower part a guiding substrate and transparent 1000 having a first surface or lower surface 1001 and a second surface or upper surface 1002 opposite each other their and parallel to the XY plane. Said guiding and transparent substrate 1000 is made of a material transparent to the electromagnetic radiation used for detection of the analyte, wherein said electromagnetic radiation is included in the spectral region from ultraviolet to far infrared, preferably included in the visible spectrum (350 – 750 nm). Said guiding and transparent substrate 1000 may have a thickness preferably between 500-1000 µm. Said transparent material constituting the transparent and guiding substrate 1000 can be or inorganic, such as, but not limited to, glass, silica, quartz, or or organic, such as, but not limited to, PMMA (Polymethylmethacrylate). The ultrasensitive optical sensor according to the present invention comprises a sensitive layer (structure, zone, region) 200 anchored to the surface upper 1002 of the transparent and guiding substrate 1000 by means of a base layer 100, in turn interposed between the surface 1002 of the substrate 1000 and the sensitive layer 200. Said base layer 100 has the function of constraining the sensitive layer 200 to the transparent and guiding substrate 1000, and may consist of a material chosen as a non-limiting example from among or silanes such as aminosilanes, epoxysilanes; or polymers, for example copolymers with succinimide functionality; which bind the sensitive layer 200 to the guiding and transparent substrate 1000, lying on a storage plane parallel to the XY plane. The sensitive structure (or sensitive layer) 200 consists of a structure periodic or pseudo-periodic, of natural origin or derivation synthetic / artificial (e.g., nano-hedgehogs, i.e. synthetic structures that present nanometric protrusions on the surface).(figure 2a) The sensitive layer 200 is not obtained by lithographic techniques in any embodiment of the present invention. Preferably, the sensitive structure is a periodic or pseudo-periodic structure. periodic of natural origin. Even more preferably, the periodic or pseudo-periodic natural structure periodic is that of pollen, such as sunflower pollen (figure 1a), although pollens from can be implemented a broad class of plants. The pollen grains implemented in the preferred embodiment of the The present invention presents a pattern on the external surface periodic or pseudo-periodic, (figure 2b), normally pseudo-periodic, of nanostructures (e.g. nanotips) having a dimension around the hundreds of nanometers, separated from each other by an interspace (intra-period pollen) of the order of magnitude of the wavelength of a radiation in the visible. In more detail, or the inter-pollen period can be controlled by maintaining the same concentration of the pollen solution but varying the density of the chemical groups on the base layer 100, i.e. the number of groups chemicals capable of binding to pollen per unit area of ​​the base layer 100; or the inter-pollen period can be controlled by changing the concentration of the pollen solution applied to the substrate 1000 by means of the base layer 100 (ie, by the number of granules pollen immobilized on the substrate per unit of surface area); or the intra-pollen period is a function of the pollen variety used or of similar natural or synthetic nanostructures employed. Preferably, the intra-pollen period varies between 100 nm and 50 µm while the The inter-pollen period varies between 100 nm and 500 µm. Pollen, once a known chemical process [1,2] has been implemented for the opening of the structure (figure 1b) and the formation / exposure of carboxylic groups free surfaces necessary for the formation of a chemical bond, is chemically immobilized on the guiding and transparent substrate 1000 by means of the base layer 100, so as to expose the periodic or pseudo-periodic nanometric structural pattern. (Figure 1c) Preferably, when the sensitive layer 200 is made of the structure natural periodic or pseudo-periodic pollen, the base layer 100 is made with compounds capable of binding the carboxylic groups present on the outer surface of the open pollen. The sensitive layer 200 is superficially coated by a first layer metallic 240. In this case, the first metal layer 240 is in direct contact with the layer sensitive 200. The first metal layer 240, in direct contact with the sensitive layer 200 and in the absence of further metal layers (which can be foreseen in further embodiments of the invention) has a thickness between 10 nm and 70 nm. The surface metallic coating (nanofilm) 240 deposited on top of the sensitive area 200 can be constituted by way of example not limiting from or a noble metal such as, but not limited to, gold, silver; or a metal multilayer such as, by way of non-limiting example, multilayer silver / gold; or a multilayer of metal oxides and metals such as for example non-limiting zirconium oxide / gold, titanium oxide / gold; or a metal alloy such as, but not limited to, gold / palladium. In one embodiment of the optical sensor (sensor chip) according to the invention the first metal layer 240 is a gold film having a thickness between 10 nm and 70 nm. In another embodiment, between the first metal layer 240, preferably in gold, and the sensitive layer 200 can be interposed a first intermediate layer 300, wherein said first intermediate layer 300 may be made by way of non-limiting example in or chromium; or titanium; or titanium oxide (TiO ); or zirconium oxide (ZrO2); and their combinations, and It has a thickness preferably between 10 nm and 30 nm. The list of possible metal materials to be used for the construction of said first intermediate layer 300 is to be understood as purely exemplary and non-limiting towards the choice of further and alternatives metals or metal pairs or metal oxides, to be implemented for reasons of instrumental performance (for example to improve its sensitivity optics) and adhesion to the substrate. According to the present embodiment where two layers are present metallic, i.e. the first metallic layer 240 and the first intermediate layer 300, the first intermediate layer 300 has a thickness of between 10 nm and 30 nm while the first metal layer has a thickness of between 10- 70 nm. The optical sensor according to the present invention comprises a layer of the 400 receptor (not shown in the figures). In more detail, on the layer metallic 240 is chemically immobilized the receptor layer 400, including an appropriate receptor of natural or synthetic origin, selectively chosen for the nature of the analyte being sought. This receptor has the function and is chosen to interact in selective manner with a specific analyte present in the matrix to be to examine. The receptor may be, for example but not limited to, an antibody or a fragment of it, a peptide, a nucleotide receptor such as the aptamer, a DNA / RNA probe or other types of natural receptors or synthetic. The receptor may further be a chemical receptor such as a polymer film on which the shape of the target molecule is printed or a mixture of target molecules when you want to measure a class of substances through the technology known as Molecularly Imprinted Polymer (MIP). Immobilization of the receptor on the surface of the metal layer can occur directly using, for example, not the chemistry of thiols is limiting (thiol groups in fact have a high affinity chemistry for noble metals such as gold and silver) or using layers intermediates based on self-assembled monolayer (SAM) that offer a wide variety of plausible chemical groupings (e.g., amino, carboxylic, epoxy). In any case, the immobilization methods are known to the expert in the field and can be chosen / adapted in relation to the nature of the receptor of interest to be anchored to the surface of the layer metallic 240. In one embodiment of the present invention, the receptor anchored to the metal layer 240 is a specific estradiol receptor (ER, code: ab82606, produced by Abcam, Cambridge, UK). Using a layer of lipoic acid covering the metal surface 240 of the biosensor, the ER receptor can be immobilized above the lipoic acid layer with the coupling agent carbodiimide [3]. In a particularly preferred form of the invention, the optical sensor according to the invention comprises: or a transparent and guiding substrate made of 1000 mm thick glass 1000 µm; or a 100 aminosilane base layer having a density of 14 2 amino groups of about 10 per cm of transparent substrate and guide 1000 adhered to the upper surface 1002 of said substrate 1000; or a sensitive layer 200 in sunflower pollen (opened and prepared according to a known technique procedure [1,2]) with a density of 4 2 pollen / cm , anchored to the substrate 1000 by means of the about 10 base layer 100; or a 240 gold metal layer having a thickness of 45 nm and deposited on top of the sensitive layer 200 using the technique of “sputter coating”, or a receptor layer 400 comprising a receptor of estradiol (ER) immobilized on the metal layer 240 for lipoic acid and carbodiimide medium. Therefore, the object of the present invention is an optical sensor (or chip sensor) made with preferably natural nanostructured systems such as sunflower pollen, or alternatively synthetic ones, such as the nano-urchins, which superficially present a periodicity or pseudo- periodicity of nanostructures capable of generating hybrid plasmonic phenomena (due to excitation by incident radiation) once covered with metal nanofilms (e.g., with a gold coating). Nanostructuring and hybrid plasmon resonance. The sensitive layer 200, being made of a periodic structure or pseudo periodic chemically linked to the base layer 100, presents superficially a spatial repetition of nanostructures (i.e., plurality of nanotips) precisely periodic or pseudo-periodic. The particular nanometric geometry presented by this system is responsible of the interaction with electromagnetic radiation and the generation of hybrid plasmonic phenomena at the metal-receptor interface. In fact, the layer sensitive 200 and the first metallic layer 240 that covers it have shape, optical properties, size and period (inter-pollen and intra-pollen) such that, when the optical signal (e.g., an electromagnetic radiation in the visible spectrum) strikes the first metal layer 240, is excited a hybrid plasmonic phenomenon (due to the mutual interaction between SPR and LSPR) at the interface between the upper face of the optical sensor and the dielectric (solution / solvent / mixture / gaseous fluid, hereinafter referred to as “bulk”) in which it is immersed or with which it is in contact, in correspondence with a certain wavelength. In particular, the hybrid plasmon is excited to a specific length wave due to the pseudo-periodicity of the nanostructures, therefore from mutual coupling between the nanotips in the case of pollen, which act like coupled plasmonic nanoantennas. In the case of pollen sunflower, for example, this occurs both within the pollen itself (intra-pollen) than on multiple contiguous pollen units (inter-pollen). The excitation wavelength of the plasmon is a function of numerous parameters, including the shape of the nanostructure, the size, the periodicity (intra-pollen period and inter-pollen period), the material metallic, the dielectric nature of the bulk and, above all, by the possible presence of analytes capable of interacting with the surface receptor of the optical sensor of the present invention. In fact, when the sensor chip of the invention, functionalized with a receptor (natural or synthetic) specific for an analyte, is placed at contact with a fluid such as a liquid matrix, a solution, air, gaseous, or an aerosol containing said analyte, the analyte binds to the receptor and changes its optical properties, i.e. the optical index refraction at the interface between the sensitive face of the optical sensor chip and the bulk, changing the plasmon resonance conditions. The method of revelation is based on the fact that the variation of optical properties due to binding to the analyte causes the wavelength to shift of plasmon resonance. This spectral shift is related to the value of concentration of the analyte in the solution. For example, in the linear segment of the dose-response curve, the resonance shift is proportional to the variation in concentration of the analyte with respect to the blank / medium (resonance value in the medium in the absence of analyte). The pseudo-periodicity of nanostructures (natural or synthetic), such as for example those of pollen or dwarf urchins, lead to the excitation of the hybrid plasmonic modes which are typical of periodic or pseudo-structures periodicals obtained through lithographic techniques aimed at creating structures regular of a few hundred nanometers. Hybrid plasmons compared to SPR and LSPR phenomena considered individually allow a improving the performance of the optical sensor to achieve, as in the case of proteins, lower detection limits. Sensor properties. In particular, as further highlighted in the Examples section (Example 2) of the In this document, the optical sensitivity of the sensor chip has been evaluated. (optical sensor) according to the present invention defined as / n where is the wavelength of the resonance, n is the refractive index of the bulk placed in contact with the upper face of the optical sensor and the differential. In the absence of a 400 receptor layer, it was found that by changing the bulk in contact with the metal surface 240 changes the wavelength at which the hybrid plasmon is induced. In fact, the plasmonic phenomenon is strictly dependent on the refractive index at the interface between the metallic medium on which it originates and the bulk in which it is immersed (or in contact with) the sensor chip. The binding sensitivity of the optical sensor was further evaluated. according to the present invention. Surprisingly, the optical sensor of the invention has shown to possess an instrumental sensitivity in the order of attomolar concentration. As will be appropriate explained in the Examples section (Example 3) of this document, the experimental evidence supporting this non-deducible sensitivity in the detection of analytes was achieved by evaluating the variation of the Hybrid plasmon wavelength on the ultrasensitive optical sensor functionalized with the estradiol receptor (ER) upon change of the concentration of the estradiol solution itself. The measuring range of the substance of interest (analyte) can be modified / customized by acting on different system parameters sensor proposed in this description, among which the possibility of change the performance / sensitivity of the optical sensor by acting on the concentration / density of pollen anchored / immobilized on the surface sensitive, on the type of pollen used (natural or synthetic), with the possibility of using different nanostructures, on the number and type of metal nanofilms used to obtain the hybrid plasmonic phenomenon, on type of natural or synthetic receptor used, with the possibility of using receptors with different efficiencies (where efficiency means the capacity of the receptor to change its refractive index when binding with the analyte occurs). Another object of the present invention is a sensor system, i.e. a a plurality of ultrasensitive optical sensors comprising periodic structures or pseudo-periodic, preferably of natural origin, having a structure like the one in figure 1e, placed side by side in solidity with each other. This sensor system comprises a plurality of optical sensors arranged on the same geometric plane and according to any geometry (scheme) lattice (Figure 3a), wherein, each optical sensor of the plurality of optical sensors of the said sensor system has a layer of the receptor 400 specific for the detection of a different analyte. A further object of the present invention is an optical multisensor (figure 3b). This optical multisensor has the same structure multilayer of the sensor chip of the invention except for the layer of the receptor 400. In more detail, the surface of the metal layer 240 of said optical multisensor is not uniformly coated with a single layer of receptor 400, but can be coated by a plurality of layers of 400 receptors, different from each other, to form distinct surface regions, according to any geometry, each specific for a given analyte. The sensor system according to the invention and the optical multisensor according to the invention are indicated in this document in a more general manner with the term array (or sensor array). Preferably, said sensor array is capable of detecting a broad class of analytes at the same time. A further object of the present invention is an apparatus also said sensor system for the qualitative and / or quantitative detection of a analyte in a medium such as a liquid / gaseous solution or air, or a aerosol, including or at least an ultra-sensitive optical sensor (also called a sensor chip) according to the invention, or an array of sensors; or at least a reference chip; or at least one source of electromagnetic radiation including in the spectral region from ultraviolet to far infrared; or at least one detection device (or detector); or at least a sample holder; in which, or the at least one source of electromagnetic radiation may be a by way of example and not limited to an LED or light source which emits in the visible; or at least one detection device (detector) can be chosen by way of non-limiting example from the group comprising one spectrometer, a spectrophotometer, or a photodiode; and or the at least one reference chip comprises the same sequence of layers present between the transparent and guiding substrate 1000 and the layer 240 of the invention sensor chip even if it is deprived of the layer sensitive layer 200 and receptor layer 400, wherein said at least one reference chip is placed on the same XY plane as the sensor chip / sensor array (the metal surfaces of the chip sensor / sensor array and reference chip lie on the same XY plane) and is used for normalization of the signal(s) obtained from the sensor chip / sensor array (e.g. for the normalization of transmission spectra). In a preferred embodiment of the sensor system described in Figure 4a, the at least one source of electromagnetic radiation is a white light lamp (i.e., emitting in the visible spectrum 350-750 nm) and the at least one detection device is a spectrophotometer. In the present embodiment of the sensor system of figure 4a, are two spectrophotometers are planned, one for capturing the signal transmitted by the sensor chip, the other for capturing the signal transmitted by the chip reference. In one embodiment of the sensor system (Figure 4b), the at least one source of electromagnetic radiation and the at least one device detection are respectively implemented within at least one first and a second optoelectronic board distinct from each other, lying on two planes parallel to the XY plane and located on opposite sides to at least one optical sensor / sensor chip / optical biosensor. Each optoelectronic board may include electronic or photonic systems aimed to improve the signal-to-noise ratio of the sensor system. example title, the optoelectronic board, source side, can include integrated optoelectronic elements for modulation of intensity or phase, wavelength tuning, and other well-known techniques to the expert in the field of telecommunications to make high-performance sensor system. The at least one first optoelectronic board comprising at least one source of electromagnetic radiation, included in the spectral region from ultraviolet to far infrared, it faces the face upper part of the at least one optical sensor / biosensor or sensor array and at least one second optoelectronic board comprising at least one detection device faces the lower surface 1002 of the substrate of the at least one optical sensor or sensor array. In another embodiment, configurations may be used based on the excitation of the hybrid plasmonic phenomenon by the field evanescent, i.e. using the 1000 substrate as the “core” of a optical waveguide and not as a transparent substrate as in the case of plasmonic nanostructures obtained through lithographic techniques [4]. In in this case, the light propagating in the waveguide in question, which for structure can be considered multimodal, it excites phenomena hybrid plasmonics using the evanescent field. In further embodiments where they are simultaneously present the invention's ultra-sensitive optical sensor chip and the reference for signal normalization, the sensor system can provide input and output from the sensitive structure (sensor chip) and from the reference chip any combination of technique lighting and detection technique. The illumination of the ultra-sensitive optical sensor and the reference chip can occur without the aid of input fibers, but with a single light source and a single input lens. The detection, however, It occurs for both structures via two respective output fibres connected to respective detectors or to respective inputs of the same detector, allowing the collection of light transmitted through the two chips and conveying it to the detector itself. In another embodiment, the sensor system consists of a configuration based on LED-photodiode coupling. The source light emits an optical signal in a wavelength range predetermined, for example in the red wavelength range, green or blue, and then the concentration of the analyte is determined on the based on the variation in intensity of the detected optical signal. In particular, in the case of the presence of the analyte, a variation in intensity is recorded signal compared to the intensity of the reference optical signal detected in absence of the analyte itself. The variation in intensity of the optical signal is linked to the change in plasmon resonance conditions due to the variation of the refractive index of the binding receptor layer to the analyte, and, therefore, to the concentration of the analyte to be detected. In another embodiment, the optical signal generated by the source bright is white light (for example a range between 350-750 nm); in in this case the concentration of the analyte is determined on the basis of the spectral shift of the plasmon resonance revealed by a detection device, e.g. a spectrophotometer, with respect to the signal optical reference detected in the absence of the analyte itself. In case the instrument setup foresees a sensor alongside the optical one ultrasensitive chip of the invention (such as the one shown in Figure 1e) a chip reference (identical to the ultra-sensitive optical sensor but without the sensitive layer 200 and the receptor layer 400), the optical signal in output from the reference chip is used to normalize the signal optical output from the sensor chip. METHOD OF REALIZATION A further object of the present invention is the method (process) for the realization of the ultrasensitive optical sensor of the invention. The method according to the present invention can be realized through the procedure described below or with slight modifications of this, which however, they are within the reach of the expert in the field. In particular, the realization of a single optical sensor will be described ultrasensitive according to the present invention comprising a structure sensitive 200, and a reference chip can be such a description extended to the realization of the sensor system (e.g., array) by any expert in the field (Figure 3). The method for the realization of the ultrasensitive optical sensor according to the This invention comprises the steps of o Prepare the substrate 1000; o Immobilize on the upper surface 1002 of the substrate 1000 with techniques known to those skilled in the art, the sensitive layer 200, preferably made of pollen [1,2] by modifying the substrate 1000 with a suitable base layer 100, appropriately chosen based on the chemical nature of the substrate 1000; o Optionally deposit the first intermediate layer 300, via techniques such as, for example, “sputter coating”, evaporation or alternative techniques for deposition of known nanoscale films to the expert in the field; o Deposit the first metal layer 240 in direct contact with the sensitive surface 200 using the sputtering technique or for evaporation, or if the optional first has been deposited intermediate layer 300, in direct contact with said first layer intermediate 300; o Chemically bind the receptor layer 400 receptor (or more receptors in the case of creating an optical multisensor (see figure 3b) to the first metal layer 240, using techniques known to the person skilled in the art. branch. Further details are described in one embodiment of the method. production of the optical sensor of the invention reported in section Examples of this document (Example 1). The manufacturing method of the reference chip is similar to that of the embodiment of the ultrasensitive optical sensor of the invention excluding but the immobilization phase of the sensitive layer 200 and the layer of the 400 receptor. Any expert in the field, on the basis of the knowledge of the known technique, you will have no difficulty in making it. The above procedure can be implemented in such a way as to obtain the sensor array of figure 3a, i.e. a plurality of optical sensors solidly supported by each other in the configuration of a system of sensors. METHOD OF USE Below, the procedure to follow for using the sensor according to the invention for determining the presence / quantity of a specific analyte in a sample. The method of use according to the present invention comprises the steps of: - Allocate the sensor chip and reference chip in the system sensor having the sample holder connected to the devices optoelectronic, that is, at least one source and at least one detector; - Acquire output signals such as spectra in transmission when illuminated by a light source white from the sensor chip and the reference chip, obtained placing the blank, i.e. the medium (bulk) without analyte, in contact with the same ones; - Normalize the output signal from the sensor chip to the signal obtained at the output of the reference chip, such as for each wavelength of the obtained spectrum; - Read the normalized signal, such as the resonance wavelength or the intensity of the transmitted radiation; - Immerse the sensor chip and the reference chip in the sample to be analyzed, whether liquid or gaseous, or in an aerosol state; - Incubate the medium containing the analyte of interest for approximately 5 minutes so that the analyte remains bound to the specific layer of sensor chip receptor; - Wash, if required by the medium being analyzed, with for example phosphate buffered saline (PBS), to remove any bonds non-specific between the surface and possible interferents; - Acquire output signals such as spectra in transmission when illuminated by a light source white from the sensor chip and the reference chip, obtained placing the white, i.e. solution without, in contact with them analyte; - Normalize the output signal from the sensor chip to the signal obtained at the output of the reference chip, such as for each wavelength of the obtained spectrum; - Read the normalized signal, such as the resonance wavelength or the intensity of the transmitted radiation; - Detect the variation of the signal with respect to the white, that is, the signal acquired, for example in PBS, before incubation with the medium containing the analyte. For example, the variation of the signal can be the shift of the wavelength of resonance, which in the linear section of the dose-response curve (usually a sigmoid) is proportional to the change of the concentration of the substance of interest (analyte). An advantage of the optical sensor of the invention is the high sensitivity to perturbations of boundary conditions. An additional advantage of the invention's ultra-sensitive optical sensor based on natural structures such as those of pollen lies in the fact that a resonance phenomenon is also triggered when air is present as surrounding medium (figure 5a) making it possible to use it even in matrices such as air or gaseous, for the detection of hazardous substances, or aerosol, for the detection of bacteria and viruses, without limiting its use to only aqueous solutions. The ultrasensitive optical sensor based on natural nanostructures, such as those of pollen or other similar structures, even artificial ones, according to the This invention is simple and easy to couple to a source light and an optical detection device, which can be arranged on opposite sides to the optical sensor in a simple and in a small space. Advantageously, the measuring range of the substance of interest (analyte) can be modified / customized by acting on different parameters of the sensor system proposed in this description, among the such as the ability to change the performance / sensitivity of the sensor chip acting on the concentration / density of pollen anchored on the surface sensitive, on the type of pollen used (natural or synthetic), with the possibility of using different nanostructures, on the number and type of metal nanofilms used to obtain the hybrid plasmonic phenomenon, on type of natural or synthetic receptor used, with the possibility of using receptors with different efficiencies (where efficiency means the capacity of the receptor to change its refractive index when binding with the analyte occurs). Ultimately, it is possible to modulate the sensitivity of the sensor system by acting on the optoelectronic setup. Advantageously, ultrasensitive optical sensors based on structures natural ones such as pollen, or artificial ones such as nano-urchins, according to the This invention is very versatile and can be combined between them according to any scheme in such a way as to achieve the sensor system (e.g., sensor array) described above. Said sensor array sensors may be able to simultaneously detect the presence and / or the concentration of several different analytes, exploiting the specificity / selectivity (induced by the receptor layer) of each individual sensor. The sensor system according to the present invention is advantageously simple to make, not requiring multiple depositions of silicone or epoxy materials hundreds of inches thick microns, nor complex systems of lenses and mirrors for coupling of light both entering and exiting the optical sensor. Advantageously, the process for making the sensor ultrasensitive optical based on natural nanostructures such as those of pollen, or artificial ones such as nano-urchins, according to the present invention, is suitable for use in large-scale production, as it can be automated and parallelized. Advantageously, compared to the processes of prior art which require complex and costly techniques (e.g., techniques lithographic methods such as electronic or optical lithography), the method for the realization of the optical sensor according to the invention is simpler, less expensive and easily scalable. Advantageously, the invention is able to implement in sensors optical of the present invention periodic or semi-periodic nanostructures periodic ready to use, made available by nature, rather than having to resort to the use of artificially derived periodic systems such as those obtained for example with lithographic techniques. However, there is no constraint on the implementation in the optical sensor. ultrasensitive of the invention of synthetic nanostructures such as, for example non-limiting example, nano-urchins (having a shape similar to that of the natural nanostructures which are the subject of this invention). Advantageously, by means of the phenomenon of plasmon resonance surface hybrid generated by the interaction between SPR plasmonic phenomena and LSPR, the optical sensor according to the present invention is capable of exhibit sensitivity in the order of attomolar concentration. Further, the ultrasensitive optical sensor / biosensor according to the invention is advantageously selective / specific towards the analyte of interest. As further detailed in the Examples section (Example 5) of this document, the sensor of the invention is capable of to discern the analyte of interest from the possible presence of potential interfering. This advantageous feature of the present invention is function of the specificity of the receptor / bioreceptor anchored to the optical sensor of the invention. It is clear, finally, that the ultrasensitive optical sensor based on nanostructures natural ones such as those of pollen, single or in a system of sensors, the sensor system and the process of manufacturing the optical sensor as well conceived are susceptible to numerous modifications and variations, all of which fall within within the scope of the invention; furthermore, all details are replaceable by technically equivalent elements. In practice the materials used, as well as the dimensions can be any depending on the needs techniques. A further object of the present invention is a portable sensor system (or portable kit) for the field measurement of one or more analytes comprising: or the ultrasensitive optical sensor according to the present invention, or a sensor array; or the reference chip or a sample holder; or at least one light source, preferably included in a optoelectronic board; or at least one detection device (or detector), preferably included in an optoelectronic board; o Instructions for use, optionally accessible remotely via an electronic medium. Optionally, the portable sensor system may include or computerized means for analyzing the data provided by the sensor comprising at least one processor, a storage memory and means for data visualization. USE OF THE SENSOR The ultrasensitive optical sensor according to the invention functionalized with an appropriate receptor (chosen according to the nature of the analyte being sought (or measured) can be used for selective presence detection and / or for the quantification / measurement / analysis of the concentration / quantity of said analyte in different matrices in numerous application fields including, for example, tumor marker diagnostics, analysis of various emerging environmental pollutants (in rivers, lakes, seas, soils agricultural, forest areas), bioterrorism or biodefense, detection of viruses and bacteria, pandemic emergencies, personalized medicine, testing Point-of-care for various analyses or pre-analyses, tests on rare diseases, measurement of explosives. EXAMPLES The exemplary and non-limiting embodiments of the scope of the present invention reported below have been obtained using as raw materials Sunflower pollen was purchased from Greer Labs (Lenoir, NC, USA). 1-ethyl-3 (3-dimethylaminopropyl) carbodiimide (EDC, 22980) and N- hydroxysulfosuccinimide (Sulfo-NHS, 24510) were purchased from Fisher Scientific Italia (Milan, Italy). -estradiol (E8875, PM 272.38), acid - lipoic acid, ethanolamine, dihydrotestosterone (DHT, PM 290.44), albumin bovine serum (BSA) were purchased from Sigma Aldrich (Milan, Italy). ER receptor (ab82606) was purchased from Abcam (Cambridge, UK). The aminosilane-coated substrates called “Nexterion A+” are purchased from SCHOTT Technical Glass Solutions GmbH (Jena, Germany). The light source (model HL-2000LL) and spectrophotometers (model FLAME-S-VIS-NIR-ES) were purchased by Ocean Insight (Orlando, FL, USA). The launch / read POFs, having a total diameter of 1 mm, were Purchased from Edmund Optics (Barrington, NJ, USA). Example 1 Exemplary embodiment of the sensor of the invention. A process for making an ultra-sensitive optical sensor of the invention comprises the following steps: o Preparation of pollen by microgel formation according to the known art procedure [1,2] which consists of an initial removal of the cytoplasm by placing 1 g of degreased pollen in a round-bottomed flask with 10 mL of aqueous KOH solution 10% (w / v). The suspension is then refluxed for 2 ha 80 °C under magnetic stirring. Then, the suspension is centrifuged at 3,500 rpm for 5 min. The supernatant is discarded and the The resulting pellet is covered with 20 mL of fresh solution of KOH at 10% (w / v). The mixture is stirred at high speed for 2 minutes and then centrifuged at 3,500 rpm for 5 minutes, repeating this washing phase for another four times. This results in the formation of the microgel by placing 10 mL of fresh KOH solution on the pellet at 10% (w / v) and transferring the contents into the round-bottomed flask, repeating the heat treatment at 80 °C for 6 h. Then the solution is centrifuged with the procedure above until the The pH of the supernatant does not approach neutrality. The pellet is then kept at 4°C until use. At the end of this procedure obtains a carboxylic activated pollen shell. o Immobilization of pollen as prepared in the previous step on amine substrates covering the glass substrate 1000 through the chemistry of carbodiimides. 20 mg of pollen are dispersed in 0.5 mL of MES buffer (100 mM MES, 0.5 M NaCl, pH 6.0) and 52 mM EDC and 138 mM sulfoNHS are added to the solution that is mixed at 120 rpm in an orbital shaker for 30 minutes. Then, the solution is centrifuged at 3,500 rpm for 5 minutes and the supernatant is replaced with buffer phosphate (10 mM phosphate buffer, 138 mM NaCl, 2.7 mM KCl, pH 7.4). A drop of activated pollen solution is deposited on the surface and incubate for 1 hour with shaking orbital. o Deposition of a 45 nm thick gold nanolayer by sputter coating technique; o Functionalization of the gold surface with the receptor of estradiol (ER). To remove any contaminants hydrocarbons from the gold surface, a plasma is applied Argon for 2 minutes at 6.8 W. During the night a 0.3 mM lipoic acid solution in water. After washing the surface in water, a solution of EDC / sNHS is applied 10 / 10 mM in 50 mM MES pH 5.5 for 30 minutes at 100 rpm in a orbital shaker. After washing in MES buffer, 4 g of estradiol receptor (ER) are incubated in phosphate buffer for 2 hours and finally passivated with 1 mM ethanolamine in water for 30 minutes. Example 2 Optical sensitivity of the sensor. The hybrid plasmon resonance spectra are reported in figure 5a. standardized version of an embodiment of the ultrasensitive optical sensor of the invention as depicted in figure 1e comprising the 1000 transparent and guiding glass substrate with a thickness of 1 mm and covered with the base layer 100 in aminosilane, the sensitive surface 200 consisting of open sunflower pollen grains (according to known technique) [1,2]) fixed on the substrate 1000 by means of the base layer 100, the 240 gold metal layer with a thickness of 45 nm to be coated (directly contact) the sensitive layer 200 but without functionalization with the layer of the 400 receptor (natural or synthetic selective layer). The measurements are were performed by placing the first metal layer 240 in contact with different “bulk” (liquid solutions of water and glycerin at different ratios of mixing) having different refractive index (n). In this example 4 spectral recording measurements were conducted with the following dielectrics: air (n=1) and 3 solutions having 3 different refractive indices listed below: o Solution 1: n = 1.332 o Solution 2: n = 1.343 o Solution 3: n = 1.355 The spectra recorded in figure 5a clearly show how at variation of the refractive index at the metal-bulk interface (due to the change in the composition of the dielectric medium in contact with the metal layer 240) changes the excitation wavelength of the hybrid plasmon. In particular, the resonance wavelength decreases as the refractive index of the bulk increases. The spectra in transmission obtained with the ultrasensitive optical sensor of the invention were normalized with the spectra transmitted through the chip reference placed in contact with the same solutions. Starting from the data contained in the graph in figure 5a, a further graph (figure 5b) showing the absolute value of the variation of the resonant wavelength towards the refractive index of the medium external both for the ultrasensitive plasmonic optical sensor based on pseudo-periodic natural nanostructures, such as that of the sunflower pollen, which of a standard comparison sensor based on a nanolattice produced by electron beam lithography (EBL). [5] Comparing the linear fitting curves obtained from the 2 sensors under examination, it appears that the optical sensor of the invention is more sensitive than the sensor comparison standard having an optical sensitivity value ( / n), corresponding to the angular coefficient of the lines in figure 5b, upper: / n of the invention sensor = 773 nm / RIU / n of the standard sensor = 547 nm / RIU Example 3 Optical sensor binding sensitivity. The curves shown in figures 6 and 7 refer to a form of realization of the ultrasensitive optical sensor of the invention such as that depicted in figure 1e including the transparent and guiding substrate 1000 glass with a thickness of 1 mm and covered with the base layer 100 in aminosilanes, the sensitive surface 200 made of granules of open sunflower pollen (according to known technique [1,2]) fixed on the substrate 1000 by means of the base layer 100, the metal layer 240 in gold 45 nm thick to coat (in direct contact) the sensitive layer 200 and further functionalized with a specific bioreceptor (layer of the estradiol receptor (estrogen receptor, ER) according to the technique reported in the description and which involves the use of 1-ethyl-3 (3- dimethylaminopropyl) carbodiimide and -lipoic acid. The measurements were performed by placing liquid solutions at different concentrations of estradiol in contact with ER anchored to the optical sensor in order to obtain a curve dose-response and demonstrate that the binding sensitivity achieved by the ultrasensitive optical biosensor based on pseudo-natural nanostructures periodicals such as those of pollen according to the present invention is of the attomolar order. The transmitted spectra obtained with the ultrasensitive optical sensor of the invention were normalized with the acquired transmitted spectra from the reference chip for the same estradiol solutions. In particular, figure 6 shows a comparative graph of spectra in transmission measured by varying the wavelength on solutions aqueous estradiol at different concentrations ranging from 0.5 aM to 1000 AM. As can be seen from the same figure, when the concentration changes of estradiol in solution, a shift in the transmission curve is observed recorded by the optical sensor demonstrating how the instrument itself is sensitive to the variation in concentration of the analyte being tested. Not only that, as the spectra in figure 6 demonstrate, the instrument is sensitive to minima variations in concentrations that even reach a tenth of the attomolar. In figure 7 a dose-response curve has been reported (interpolated with classical analyte-receptor interaction model, i.e. model of Langmuir) obtained from the absolute value of the variation of the hybrid plasmon resonance length of the sensor of the invention in function of estradiol concentration. Example 4 Configuring a sensor system in the presence of the optical sensor chip and the reference chip. Figure 4 shows a schematic example of a sensor system. comprising the ultrasensitive optical sensor of the invention (as prepared in example 1) and the reference chip (i.e. an identical one but without pollen, i.e. without nanostructures) used for the normalization of spectra. In this case, the sensor system features two multimode fibers (total diameter of 1 mm) of input to illuminate the ultra-sensitive sensor and reference chip and two respective fibers multi-mode output to collect the light transmitted by both. Example 5 Selectivity of the optical sensor of the invention. The specificity / selectivity of the optical sensor was further measured ultrasensitive of the invention having the thickness of the metal layer 240 of gold equal to 45 nm, in direct contact with the sensitive surface 200, in turn made up of open sunflower pollen grains (second known technique) immobilized on the substrate 1000, and functionalized on the metal layer 240 with a specific bioreceptor for estradiol (estrogen receptor, ER) according to the technique reported in the description and which involves the use of lipoic acid and carbodiimide. In particular, the selectivity of the biosensor was evaluated by comparing in a vertical bar graph (figure 8) the variation of the wavelength of hybrid surface plasmon resonance of the optical sensor present invention put in contact with 3 different solutions: or an aqueous solution of 10 aM estradiol; or an aqueous solution of 1 fM bovine serum albumin (BSA); and or an aqueous solution of 1 fM dihydrotestosterone (DHT). As can be seen from figure 8, the optical sensor of the invention, by means of of the intrinsic specificity of the estradiol bioreceptor (ER), has showed a clear selectivity towards the analyte of interest, i.e. estradiol, despite the use of interferents at considerably higher concentrations higher (100 times more concentrated) than that of estradiol. Bibliographic references [1] https: / / doi.org / https: / / doi.org / 10.1016 / j.apmt.2020.100702; [2] https: / / doi.org / 10.1038 / s41467-020-15294-w; [3] Bioconjugate Techniques 3rd Edition - July 25, 2013; Author: Greg T. Hermanson; Hardback ISBN: 9780123822390; eBook ISBN: 9780123822406; [4] https: / / doi.org / 10.3390 / nano11081961. [5] [https: / / doi.org / 10.1364 / PRJ.424006].

Claims

CLAIMS 1. An optical sensor for detecting an analyte in a sample by hybrid plasmon resonance, said sensor comprising: o a transparent guiding substrate 1000 having a lower surface 1001 and an upper surface 1002 parallel and opposite to each other, said substrate being transparent to the electromagnetic radiation used for detecting the analyte, said electromagnetic radiation being in the spectral region from the ultraviolet to the far infrared; o a base layer 100 in contact with the upper surface 1002 of said substrate 1000; o a sensitive layer 200 chemically immobilized on the transparent guiding substrate 1000 by the base layer 100; o a first metal layer 240 coating the upper surface of said sensitive layer 200, o a receptor layer 400 chemically bonded to the upper surface of said first metal layer 240;wherein: the sensitive layer 200 comprises a plurality of nanostructured systems, selected from natural, synthetic, periodic, pseudo-periodic systems, capable of generating, in combination with the metal layer 240 by interaction with electromagnetic radiation, hybrid surface plasmon resonances, and wherein: the receptor layer 400 comprises a receptor selected from: an antibody or a fragment thereof, a peptide, a nucleotide receptor such as an aptamer, a DNA / RNA probe, a chemical receptor such as a polymeric film on which the shape of the target molecule or a mixture of target molecules is printed. Ρ8192ΓΓ00 PRAXI Intellectual Property SpA; 2. The optical sensor according to claim 1 wherein: the material with which the transparent and guiding substrate 1000 is made is selected from glass, quartz, silica, polymethyl methacrylate (PMMA), and is transparent to visible radiation in the range 350-750 nm.

3. The optical sensor according to any of claims 1-2 wherein: the material from which the base layer 100 is made is selected from either silanes, preferably selected from aminosilanes, epoxysilanes; or polymers, preferably selected from copolymers with succinimide functionality.

4. The optical sensor according to any of claims 1-3 wherein: the material with which the first metallic layer 240 is made is selected from noble metals, preferably gold and silver, metallic multilayers, multilayers of metal oxides and metals, metallic alloys, and has a thickness between 10-70 nm; 5. The optical sensor according to any of claims 1-4 further comprising a first intermediate layer 300 interposed between the sensitive layer 200 and the first metal layer 240, wherein said intermediate layer 300 is made of a material selected from chromium, titanium, titanium oxide (TiO2), zirconium oxide (ZrO2) and combinations thereof, and has a thickness of between 10-30 nm.

6. The optical sensor according to any of claims 1-5 wherein the nanostructured systems of the sensitive layer 200 are pollen grains, preferably sunflower, preferably having an inter-pollen period between 100 nm and 500 pm and an intra-pollen period between 100 nm and 50 pm.

7. The optical sensor according to any of the preceding claims Ρ8192ΓΓ00 PRAXI rntellectual Property SpA having a sensitivity in the order of attomolar concentration.

8. The optical sensor according to any preceding claim comprising: o the transparent and guiding layer 1000 made of glass with a thickness of 1000 µm; o the first base layer 100 made of aminosilane; o the nanostructured sensing layer 200 made of sunflower pollen grains having an inter-pollen period of between 100 nm and 500 µm and an intra-pollen period of between 100 nm and 50 µm; o the first metallic layer 240 made of gold with a thickness of 45 nm; o the receptor layer 400 made of a specific bioreceptor for estradiol (ER).

9. Array consisting of a plurality of optical sensors according to any of the preceding claims, wherein said sensors, integrally arranged next to each other, are arranged on the same geometric plane, and wherein each optical sensor of the plurality of optical sensors has a receptor layer 400 specific for the detection of an analyte.

10. Array having the same multilayer structure as the optical sensor according to any of claims 1-8 with the exception of the receptor layer 400, wherein the surface of the metal layer 240 is not uniformly coated by a single receptor layer 400 but is coated by a plurality of receptor layers 400, different from each other, to form distinct surface regions, according to any geometry, each specific for a given analyte.

11. A sensor system for detecting an analyte in a sample comprising: Ρ8192ΓΓ00 PRAXI Intellectual Property SpA or at least one optical sensor according to any of claims 1-8 or an array according to any of claims 9-10; or at least one source of electromagnetic radiation, preferably in the visible range; or at least one detection device selected from spectrophotometers, spectrometers, photodiodes; or at least one reference chip, said at least one reference chip for spectral normalization being identical to the at least one optical sensor except for the absence of the sensitive layer 200 and the receptor layer 400; or at least one sample holder.

12. The sensor system according to the preceding claim wherein the at least one source of electromagnetic radiation and the at least one detection device are respectively implemented within at least a first and a second optoelectronic board distinct from each other.

13. The sensor system according to any of claims 1112 further comprising computerized means for analyzing the data provided by the sensor in turn comprising at least a processor, a storage memory and means for displaying data.

14. The sensor system according to the preceding claim wherein the means for displaying data are local, such as a display, or remote, such as a computer, smartphone, or other electronic device.

15. A computer program which, when executed, instructs the sensor system according to any of claims 11-14 to perform a method for determining an analyte in a Ρ8192ΓΓ00 PRAXI rntellectual Property SpA sample.

16. Computer-readable storage medium comprising the program according to claim 15.

17. A computer system comprising the computer program according to claim 15, wherein the computer system may optionally be a tablet or a smartphone.

18. A method for determining an analyte in a sample by the sensor system according to any of claims 11-14 comprising the steps of: o Locating the at least one optical sensor and the at least one reference chip in the sensor system provided with a sample holder connected to the at least one source and the at least one detector; o Acquiring the output signals from the optical sensor and the reference chip, obtained by placing said optical sensor and said reference chip in contact with or immersed in the medium, said medium being the sample in the absence of the analyte; o Normalizing the output signal from the optical sensor with respect to the signal obtained at the output of the reference chip; o Reading the normalized signal; o Immersing the optical sensor and the reference chip in the sample to be analyzed; o Incubating the sample so that the analyte binds to the receptor layer 400 of the optical sensor;o Optionally, wash the optical sensor to remove any interferents; o Acquire the output signals from the reference chip and the optical sensor to which the analyte to be examined is bound, said signals being obtained by placing said optical sensor and Ρ8192ΓΓ00 PRAXI rntellectual Property SpA said reference chip in contact with or immersed in the analyte-free medium; o Normalize the output signal from the optical sensor with respect to the signal obtained from the reference chip; o Detect the variation of the signal with respect to the medium.; 19. A portable kit for determining an analyte in a sample comprising: o a sensor system according to any of claims 11-14; o Instructions for use, optionally remotely accessible through an electronic means. o Optionally, computerized means for analyzing the data provided by the sensor comprising at least a processor, a storage memory and means for displaying data.

20. Use of the optical sensor according to any of claims 1-8, or of the array according to any of claims 9-10 or of the sensor system according to any of claims 11-14 for determining the presence or quantity of an analyte in a sample, wherein said sample may be a fluid selected from a liquid or gaseous solution, or an aerosol.

21. Use according to the preceding claim in an application field selected from: tumor marker diagnostics, analysis of various emerging environmental pollutants (in rivers, lakes, seas, agricultural land, forest areas), bioterrorism or biodefense, detection of viruses and bacteria, pandemic emergencies, personalized medicine, point-of-care tests for various analyses or pre-analyses, testing for rare diseases, measurement of explosives.