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    • 专利摘要:
    A microfluidic sensor for the detection of analytes in objects is described, comprising a contact surface that can be coupled to a surface of the object, an inlet hole in the inlet contact surface of fluids emitted by the object, a first reservoir that stores a fluid ionic in the form of a polymeric matrix. The polymeric matrix comprises a reactive substance that changes color when it comes into contact with the analytes of the fluids emitted by the object. Furthermore, it comprises at least one first microfluidic conduit that connects the inlet orifice with the first reservoir. Also described is an analyte detection system, a method for manufacturing the microfluidic sensor, and the use of the microfluidic sensor for analyte detection in artwork. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2802290A1
    申请号:ES201930628
    申请日:2019-07-05
    公开日:2021-01-18
    发明作者:Benito López Fernando；Ortiz De Pinedo Kepa Castro；Ilaria Costantini；Laso María Dolores Rodríguez
    申请人:Euskal Herriko Unibertsitatea；
    IPC主号:
    专利说明:

    [0002] The present invention falls within the techniques for the detection of analytes, for example, ammonia, chlorides, nitrates, carbonates, bicarbonates, sulfates, dissolved cations, among others, in objects, for example, works of art, buildings, construction materials , etc. In particular, it refers to a microfluidic sensor capable of detecting the presence of certain analytes in the objects that it monitors in a completely autonomous, efficient and real-time way, and the microfluidic sensor being located in direct contact with the object to be monitored.
    [0005] Research on the conservation of cultural heritage is increasingly focused not only on the identification of degradation factors that affect heritage but, above all, on the use of innovative techniques for climate and environmental monitoring through air monitoring systems and pollutant levels. These techniques make it possible to establish a risk level for the conservation of movable and immovable works due to the presence of the aforementioned degradation factors.
    [0006] Nowadays, a wide variety of pollutant monitoring instruments are emerging that make use of devices based on miniature designed systems (transducers, portable and integrated sensors). These systems typically use remote transmission of the analytical signal, allowing the experimental data to be shared in real time. In addition, this implies a saving of time for researchers (collecting data on the ground may take even a few days), as well as greater involvement of the end user, who will be able to know the possible damages, the origin of the same and even restoration and conservation strategies.
    [0007] One of the most recently developed devices in this direction is the MEMORI ® dosimetry technology for monitoring pollutants in interior spaces proposed by Gr 0 ntoft et al. [Assessment of indoor air quality and the risk of damage to cultural heritage objects using MEMORI ® dosimetry, Studies in Conservation, 61, 70-82]. This technology has been developed as a tool to measure and assess the risk of degradation of cultural heritage objects stored indoors due to exposure to atmospheric pollutants (eg, O 3 , SO 2 and NO 2 ). However, as highlighted in recent research by Valentini et al. [Smart Portable Devices Suitable for Cultural Heritage: A Review, Sensors, 2018, 18, 2434; doi: 10.3390 / s18082434], sensors have not been designed yet that can be applied directly to the surface of works of art and that are capable of diagnosing local damage to them.
    [0008] In addition, there are tattoo sensors in the state of the art such as that proposed by Torsi et al. [Organic field-effect transistor sensors: a tutorial review, Chemical Society Reviews, 42, 8612-8628] based on organic semiconductor field-effect transistors. These sensors monitor the physical and chemical changes that occur during the iteration of contaminated materials. It is also known to use tattoo sensors, applied to human skin, to monitor sports performance by analyzing the athlete's sweat.
    [0009] Colorimetric analyte detection methods have been applied in the state of the art as a rapid tool for the determination and detection of the concentration of various types of analytes in various types of matrices. The colorimetric detection technique uses the ability of the reagents present in the matrix to associate with the analytes of interest, generating as a result a new component of a different color than the original matrix (colored reaction). The intensity of this reaction will depend directly on the analyte concentration. However, these colorimetric detection systems are generally complicated devices that consist of reagent reservoirs, pumps and valves for controlling the flow of liquids in the device and detector modules, making them expensive and unsuitable for use at the site of contamination. or on the object to be monitored.
    [0010] Microfluidic devices are devices in which fluids are managed and controlled at the microscale or mesoscale in a precise way. The behavior of fluids on the microscale can differ from macrofluids in factors such as surface tension, energy dissipation and fluid resistance. For example, in microfluidic devices (channels or conduits with diameters of around 100 nanometers to several hundred micrometers) the Reynolds number, which characterizes the presence of turbulent flow, is extremely low so the laminar flow remains constant. .
    [0011] Microfluidics is a multidisciplinary field that combines engineering, physics, chemistry, biochemistry, nanotechnology and biotechnology, for applications of high industrial, economic and social value, and to achieve functional devices with multiplex capacity, automated and high performance.
    [0012] The use of such microfluidic devices opens up the possibility of rapid, precise and punctual monitoring of the contaminants and degradation factors existing in works of art by means of miniaturized components, in a simple way, which are concepts that should be ideally implemented in the activities of heritage conservation and monitoring.
    [0013] However, to date there are no known solutions that use microfluidic devices for the monitoring of said pollutants and degradation factors in works of art and heritage. Currently, there are no solutions capable of continuously monitoring cultural heritage (buildings, sculptures, paintings, photos, wall paintings, ...) taking advantage of all the beneficial characteristics of microfluidic devices (small dimensions, portability, detection in situ , continuous monitoring, low cost, ease of use, etc.).
    [0016] Therefore, there is a need, for example, in the fields of conservation and restoration (cultural heritage), for sensors that can be attached directly to the surface of works of art or to the built-in surface of cultural heritage and that can diagnose or anticipate local damage. These types of sensors allow continuous monitoring, at the point of need, of works of art. Additionally, these sensors can be combined with environmental sensors to provide holistic monitoring of the artwork and its surroundings.
    [0017] The invention provides a solution to the aforementioned problems by means of a microfluidic sensor for the detection of analytes in objects, an analyte detection system, a process for manufacturing a microfluidic sensor for the detection of analytes in objects and the use of the microfluidic sensor for the detection of analytes in fluids emitted by surfaces of objects, such as works of art or construction materials, according to the set of claims.
    [0018] A first aspect of the invention relates to a microfluidic sensor for the detection of analytes in an object. The microfluidic sensor comprises a contact surface configured to be coupled to a surface of the object, for example, by an adhesive. Furthermore, it comprises an inlet orifice in the contact surface for the entry of fluids, for example liquids or gases, emitted by the surface of the object and a first reservoir that stores an ionic fluid in the form of a polymeric matrix. The polymer matrix comprises a reactive substance that is configured to change color when it comes into contact with at least one analyte present in fluids emitted from the surface of the object. The microfluidic sensor also comprises at least one first microfluidic conduit that connects the inlet port with the first reservoir. The microfluidic sensor is small in size and flexible so that it can be easily attached to the surface of the object of interest, regardless of the geometry of that surface. This at least one conduit or microfluidic channel conducts the liquid and gases generated by the object from the surface of the object itself, through the inlet orifice, to the first reservoir where the polymer matrix with the reactive substance is located.
    [0019] A user can visually detect the color change in the polymeric matrix caused by the presence of the analyte of interest. Furthermore, a plurality of microfluidic sensors could be placed, each with a polymeric matrix that stores a different reactive substance to detect the presence of different analytes on the same surface of an object of interest, for example, a work of art. In this way, and given the small size of microfluidic sensors, the presence of a plurality of degradation factors can be monitored in a very small space.
    [0020] In a particular embodiment, the reactive substance is configured to change color by reaction with the at least one analyte at an intensity proportional to the concentration of the analyte, the concentration-intensity relationship being linear, quadratic, or any other. Therefore, the higher the concentration of the analyte of interest, the greater the intensity of the color resulting from the chemical reaction between the analyte and the reactive substance in the polymer matrix.
    [0021] In another particular embodiment, the microfluidic sensor comprises a second reservoir configured to store moisture from the first reservoir and at least one second microfluidic conduit that connects the first reservoir with the second reservoir. This second conduit or microfluidic channel, which transports the moisture existing in the first reservoir to the second reservoir, and the second reservoir prevent moisture from damaging the reactive substance or the polymeric matrix that contains it.
    [0022] In another particular embodiment, the microfluidic sensor is formed by a first pressure sensitive adhesive sheet that has a first hole in correspondence with the inlet hole of the microfluidic sensor. Furthermore, it comprises a polymethylmethacrylate (PMMA) sheet comprising the inlet hole, the first reservoir and the at least one first microfluidic conduit, a second pressure-sensitive adhesive sheet that has a second hole in correspondence with the first reservoir and a sheet cyclic olefin polymer (COP). The first pressure sensitive adhesive sheet adheres to the object and the polymethylmethacrylate sheet and the second pressure sensitive adhesive sheet adheres to the polymethylmethacrylate sheet and the cyclic olefin polymer sheet. The adhesive on the face of the first pressure sensitive adhesive sheet is selected so that it does not damage the surface of the object to which it is adhered, especially if the microfluidic sensor adheres to works of art. As an alternative to PMMA and COP, these microfluidic sensor sheets could be made of polydimethylsiloxane (PDMS) or other materials compatible with macroscale plastic production that are transparent.
    [0023] In another particular embodiment, the PMMA sheet comprises the second reservoir and the at least one second microfluidic conduit.
    [0024] In another particular embodiment, the analyte is ammonia and the reactive substance is a water-soluble copper (II) salt. In this way, the microfluidic sensor is able to detect the presence of ammonia in the object to which it is attached, for example, a work of art such as a historic building, a sculpture, a painting, etc. In another particular embodiment, the water soluble copper salt is copper (II) chloride.
    [0025] In another particular embodiment, the analyte is selected from a group comprising: chlorides, nitrates, carbonates, bicarbonates, sulfates, dissolved cations, and any combination of the above. More generally, the analyte could be anyone whose anions can be analyzed in a colorimetric type sensor.
    [0026] In another particular embodiment, the polymeric matrix is formed from a compound selected from a group comprising an ionogel, a hydrogel, a porous polymer or polyionic liquids. More generally, the polymeric matrix could be made of any material capable of retaining the sensor material, that is to say the reactive substance, and whose porosity makes it suitable to retain liquids or gases.
    [0027] In another particular embodiment, the ionogel is formed by ions selected from a group comprising colonium, imidazolium, phosphonium, ammonium, pyridinium pyrrolidinium cations, among others, with a wide variety of anions, for example, tetrafluoroborates, hexafluorophosphates, phosphates, perfluorophosphates, perfluoroamides, bis (oxalate) borates, among others.
    [0028] In another particular embodiment, the microfluidic sensor is transparent. The entire device is transparent to allow colorimetric detection (the color change) in the polymer matrix. Said colorimetric detection could be done visually or, by means of a detection unit configured to detect the color change of the reactive substance, such as, for example, infrared spectrometers or Raman spectrometers, among others.
    [0029] In another particular embodiment, the object is a work of art such as, for example, a painting, a wall painting, a sculpture, a historic building, construction materials, etc.
    [0030] A second aspect of the invention refers to a system for detecting analytes in an object, comprising a microfluidic sensor as described above and a detection unit configured to detect the change in color of the reactive substance in the first microfluidic sensor reservoir.
    [0031] In some embodiments, the detection unit comprises a camera for monitoring the microfluidic sensor and a digital image processing module for detecting the color change of the reactive substance in the first reservoir of the microfluidic sensor from the images captured by the camera. . The camera could be a video camera or photographic camera configured to capture images from the microfluidic sensor periodically.
    [0032] In some embodiments the detection unit is selected from a group comprising an ultraviolet-visible spectrometer, an infrared (IR) spectrometer, and a Raman spectrometer to allow colorimetric / IR / Raman detection, respectively, of the reactive substance.
    [0033] A third aspect of the invention relates to a process for manufacturing a microfluidic sensor for the detection of analytes in objects, as described above. The method comprises providing a contact surface configured to be coupled to a surface of the object and providing an inlet port in the contact surface for the entry of fluids emitted by the surface of the object. In addition, it comprises providing a first reservoir that stores an ionic fluid, the ionic fluid comprising a reactive substance that is configured to change color when it comes into contact with at least one analyte present in the fluids emitted by the surface of the object and providing at least a first microfluidic conduit connecting the hole to the first reservoir.
    [0034] In some embodiments, the method of manufacturing the microfluidic sensor comprises providing a first pressure-sensitive adhesive sheet comprising the contact surface and having a first hole in correspondence with the inlet port of the microfluidic sensor, providing a polymethylmethacrylate sheet comprising the inlet port, the first reservoir and the at least one first microfluidic conduit, providing a second pressure sensitive adhesive sheet having a second port in correspondence with the first reservoir, and providing a cyclic olefin polymer sheet. In such embodiments, the first pressure sensitive adhesive sheet adheres to the polymethylmethacrylate sheet and is configured to adhere to the object and the second pressure sensitive adhesive sheet adheres to the polymethylmethacrylate sheet and the cyclic olefin polymer sheet.
    [0035] A fourth aspect of the invention refers to the use of the microfluidic sensor for the detection of analytes in fluids emitted by surfaces of works of art such as, for example, paintings, wall paintings, sculptures, historical buildings, other types of works of art and heritage. It also refers to the use of the microfluidic sensor for the detection of analytes in fluids emitted by surfaces of building materials.
    [0036] The microfluidic sensor for detection of analytes in objects, the analyte detection system, the procedure for manufacturing a microfluidic sensor for the detection of analytes in objects and the use of the microfluidic sensor for the detection of analytes in fluids emitted by surfaces of objects, such as for example works of art or construction materials, it presents a series of advantages compared to the state of the art. Said advantages are: it allows the monitoring and control of exudates in objected, such as works of art, that may be affected by different degradation factors or environmental contamination by means of wearable microfluidic technology and in an automatic and autonomous way. It also allows the use of image monitoring techniques such as video cameras or photographic analysis or in combination with even more precise and specific detection techniques such as Raman, IR, UV-Vis spectroscopy, among others, for monitoring and control of these degradation factors. Furthermore, it is manufactured from flexible, low-cost materials and can be easily modified depending on the analyte to be detected and the object on which it is to be placed. In addition, its use has other advantages, among which it is easy to store, transport and is disposable, which is very suitable for cheap and quick on-site diagnosis by untrained personnel, without the need for power sources or electronic components. The microfluidic sensor is very small, portable, uses small sample volumes thereby reducing the amount of reagents, is highly sensitive and reliable, and provides a response in a short period of time.
    [0039] To complete the description and in order to improve understanding of the invention, a set of figures is provided. Said figures form an integral part of the description and illustrate different embodiments of the invention, which should not be construed as limiting the scope of the invention, but rather as examples of how the invention can be carried out.
    [0040] Figure 1 shows a front view of an example of a microfluidic sensor for analyte detection, attached to a wall.
    [0041] Figure 2 shows an exploded perspective view of the example of a microfluidic sensor of Figure 1.
    [0042] Figure 3 shows a view of an example of an object analyte detection system.
    [0043] Figure 4 shows the absorption spectra of the ionogel (black / solid line), of the ionogel after adding copper chloride (blue / striped) and of the ionogel with copper chloride after reacting with ammonia (red / dotted). Figure 5A shows an experiment in which four microfluidic sensors are exposed to solutions with different concentrations of ammonium nitrate (through the exudate of the mortar) and a reference sensor (where no ammonium nitrate is used, only water). Figure 5B shows a histogram showing the mean values of the color parameter "H" for the five microfluidic sensors (number of measurements of the "H" value in the sensor equal to three).
    [0046] Figure 1 shows a front view of an example of a microfluidic sensor 100 for analyte detection, for example the ammonia released after reacting ammonia with mortar, attached to a wall 101. It should be understood that the microfluidic sensor 100 represented in the figure 1 may include additional components and that some of the components described herein may be removed and / or modified without departing from the scope of the microfluidic sensor 100.
    [0047] The microfluidic sensor 100 is coupled to a wall 101 for detecting and monitoring the impact of the ammonium cation on the construction materials of said wall 101. The microfluidic sensor 100 comprises an inlet orifice 102 of the exudates from wall 101, these exudates may contain the ammonium cation, in addition to other anions, cations and substances such as, for example, water and ammonia. The microfluidic sensor 100 also has a first reservoir 103 where an ionogel 104 is stored in ionic liquid in the form of a polymeric matrix that acts as a support to contain a reactive substance, in this case, copper chloride (CuCh) although it could be any soluble salt of Cu2 +. The reactive substance is embedded in the polymeric matrix, where the structure of the polymeric matrix allows the storage of the reactive substance for long periods of time without deteriorating while allowing it to react with the analyte of interest to function as a colorimetric sensor.
    [0048] The first reservoir 103 has a configuration that allows exudates, liquids and / or gases, to pass through the ionogel 104. The microfluidic sensor 100 is made of transparent material to allow colorimetric / IR / Raman detection in the polymeric matrix and presents a low stiffness that allows it to be attached to surfaces with different geometries.
    [0049] The microfluidic sensor 100 further comprises a first microfluidic conduit 105 that communicates the inlet orifice 102 with the first reservoir 103 for transporting exudates from the wall 101 to the first reservoir 103. Furthermore, it comprises a second reservoir 106 to store moisture coming from the first reservoir 103 and transported from the first reservoir 103 via a second microfluidic conduit 107.
    [0050] The ionogel 104 could be formed by ionic liquids based on thiazolium, benzothiazolium, phosphonium and imidazolium, among others. In addition, ionogel 104 may contain other reactive substances to control other analytes of interest, such as Hydrogen cations for the detection of pH or variations in the redox potential, chlorides, nitrates, nitrites, carbonates, bicarbonates, sulphates, dissolved cations, among others.
    [0051] As an alternative to ionogel 104, the first reservoir 103 could contain hydrogels, porous polymers or poly-ionic liquids in the form of a polymeric matrix, depending on the detection needs of the microfluidic sensor 100. Hydrogels are polymerized, cross-linked, porous structures, and with properties hydrophilic capable of retaining a significant fraction of water within it. Hydrogels are generally prepared from hydrophilic monomers, although hydrophobic monomers can also be used to regulate properties for specific applications. For example, the hydrogels could be polyacrylamides.
    [0052] In this example of a microfluidic sensor 100, the copper (II) chloride reacts with the ammonia from the exudates of the wall 101 so that the copper (II) cation forms a stable compound with the ammonia and changes the color to greenish-yellow. to blue, according to the reaction:
    [0053] CuCl 2 + 4 NH3 ^ [Cu (NH3) 4] Ch
    [0054] Gradually, the copper chloride (CuCh) reacts with ammonia vapors, and when the reaction is complete and the metal complex of copper and ammonia ([Cu (NH 3 ) 4 ] Cl 2 ) is formed, the sensor changes color from greenish-yellow to blue.
    [0055] In this example, ionogel 104 is made using IL's (IO-1) 1 -ethyl-3-methylimidazolium ethylsulfate. The ionogel is synthesized by mixing two monomers, a first linear monomer (N-isopropylacrylamide) and a second crosslinking monomer (N, N'-methylene-bisacrylamide) to give the three-dimensional structure and that thanks to its positive and negative charges ensures that the Polymeric matrix structure does not collapse while improving the plasticity of the gel. In addition, a photoinitiator (2,2-Dimethoxy-2-phenylacetophenone) is added to induce photopolymerization at a wavelength of 365 nm. To do this, with a mechanical pipette, 75 ^ L of the solution with the two monomers together with the photoinitiator is uniformly placed on a support. Subsequently, the solution is subjected to a photopolymerization process with a UV-VIS lamp of 365 nm wavelength for 5 minutes. The ionogel 104 resulting from the ionic liquids is washed with isopropanol and distilled water and dried with absorbent paper to remove any remaining unreacted monomers and any other reagents. Then, 75 ^ L of a 0.3 M solution of copper chloride in ethanol is poured onto the ionogel for drying. Finally, the sensor is washed with distilled water and dried with absorbent paper.
    [0056] Figure 2 shows an exploded perspective view of the example microfluidic sensor 100 of Figure 1. The microfluidic sensor 100 is manufactured using multilayer lamination protocols.
    [0057] The microfluidic sensor 100 consists of four layers. In principle, the layers that make up the microfluidic sensor 100 can be of any material as long as it is inert to the materials with which it will come into contact, that is, it does not react, and does not interfere with the chemistry of the polymeric matrix, reactive substances contained in the polymeric matrix, nor with the chemical compounds from the exudates of the object to be monitored. Examples of suitable plastic materials for the layers are, among others, high density polyethylene, low density polyethylene, polyethylene terephthalate, polyvinyl chloride, polypropylene, polystyrene or polycarbonate, polymer or copolymer of cyclic olefins or acrylic resins.
    [0058] In this example, the microfluidic sensor 100 comprises a first pressure sensitive adhesive layer 108, cut with a cutting plotter (Graphtec CE5000-40 Craft Robo Pro), which contains a first hole 109 in correspondence with the inlet hole 102. The first pressure sensitive adhesive layer has both adhesive faces, with an outer face that adheres to the object to be monitored, in this case to wall 101, and an inner face that adheres to an inner layer of polymethylmethacrylate (PMMA) 110 The inner layer of PMMA 110 is manufactured using a CO 2 laser ablation system (Laser Micro-machining Light Deck). This inner layer of PMMA comprises the inlet hole 102, the first microfluidic conduit 105, the first reservoir 103, the second microfluidic conduit 107 and the second reservoir 106. The inner PMMA layer has greater rigidity, it is slightly thicker (for ahem, about 1mm) and presents a higher mechanical resistance than the other three layers that make up the microfluidic sensor 100.
    [0059] The second microfluidic conduit 107 that connects the first reservoir 103 with the second reservoir 106 carries the moisture that reaches the ionogel 104 to the second reservoir 103 where it is stored. By removing moisture from the polymer matrix, the life of the microfluidic sensor 100 is extended. Furthermore, it can be used as a qualitative way to measure the moisture exuded by the object to be monitored. The dimensions of the second reservoir 106 may vary depending on the object to which the microfluidic sensor is attached, being larger when a greater amount of moisture exuded by the object is expected.
    [0060] The microfluidic sensor 100 has a second pressure sensitive adhesive layer 111 which adheres on one side to the inner PMMA layer 110 and on the other side to a layer of cycloolefin polymer (COP) 113. The second pressure sensitive adhesive layer 111 has an orifice 112 in correspondence with the first reservoir 103 so that the space of the first reservoir 103 is defined by the first pressure sensitive adhesive layer 108, the PMMA layer 110 and the COP layer 113. This COP layer 113 allows full transparency of the detection zone of the first reservoir 103 and maintains the ionogel 104 in the front and outermost zone of the microfluidic sensor 100. Preferably, all the layers of the microfluidic sensor 100 are made of a transparent material.
    [0061] In this specific example, for the manufacture of the microfluidic sensor 100, the first pressure sensitive adhesive layer 108 is placed and the PMMA layer 110 adheres to it. Then, 5 j L of IL's (IO-1) ethyl sulfate of 1 -ethyl-3-methylimidazolium in the first reservoir 103 and photopolymerization is carried out with a UV-VIS lamp for 1 min to form the ionogel 104. Alternatively, the ionogel 104 could be obtained in a separate container and from it taken an amount that is it would deposit in the first reservoir 103 where the photopolymerization would take place. The ionogel 104 is then washed with isopropanol and distilled water and dried with absorbent paper. Subsequently, a 0.3 M solution of copper chloride in ethanol is added to the ionogel 1045 | jL and the ionogel 104 is washed again with water and dried. Finally, the second pressure sensitive adhesive layer 111 and the COP layer 113 are placed. Finally, the microfluidic sensor 100 is placed on the surface to be monitored. This design allows simple ocular visualization of the color change in the polymer matrix containing the ionogel 104. It also allows the use of electronic detection units, eg, spectrometers, for the detection of the color change in the polymer matrix.
    [0062] The amount of ionogel 104 that is deposited in the first reservoir 103 is variable and will depend in each case on the design of the microfluidic sensor 100.
    [0063] Although Figures 1 and 2 show a microfluidic sensor 100 with a very specific geometry and arrangement of elements, the dimensions of the microfluidic sensor 100 can be variable and there is no particular limitation in this regard. The size of the microfluidic sensor 100 may vary depending on the analysis requirements and the object on which it is to be placed, among other parameters. In a particular embodiment, the device is 1.5 mm thick and 3x3 cm in size. Likewise, the dimensions, arrangements and shapes of the microfluidic reservoirs, apertures and conduits can also vary in the microfluidic sensor 100, without there being any particular limitation in this regard.
    [0064] Figure 3 shows a view of an example of analyte detection system 200 on an object, for example, a wall 201, including the microfluidic sensor 202 and a detection unit 203 configured to detect the color change of the reactive substance in the first reservoir of the microfluidic sensor 202. It should be understood that the detection system 200 depicted in Figure 3 may include additional components and that some of the components described herein may be removed and / or modified without departing from the scope of detection system 200.
    [0065] The analyte detection system 200, for example, ammonia, in a construction material of a building, for example, the wall 201 of a building, comprises a microfluidic sensor 202, for example, as described in Figures 1 and 2 , coupled to said wall 201. Furthermore, it comprises a detection unit 203 configured to detect the color change in the microfluidic sensor 202. This detection unit 203 is formed by an ultraviolet-visible spectrometer (not shown) connected to a camera of video 204 that monitors the microfluidic sensor 202. The detection unit 203 also houses a digital image processing module integrated into the spectrometer that is configured to detect the color change of the reactive substance in the microfluidic sensor 202. Both the camera video module 204 such as the spectrometer and the digital image processing module are integrated into the housing of the detection unit 203.
    [0066] The detection unit 203 has wireless communication means, for example, a Bluetooth or WiFi connection, to send the results of the captured image processing to a remote device 205 such as a computer, a mobile phone, an iPad. , a PDA, etc.
    [0067] Alternatively, the detection unit 203 could have an infrared spectrometer or a Raman spectrometer also connected to the video camera 204 and the digital image processing module integrated into the spectrometer. In other examples, alternatively to the video camera 204, the detection unit could have a photographic camera programmed to take images of the microfluidic sensor 202 periodically.
    [0068] Said detection unit 203 could be coupled to wall 201 and located in proximity to microfluidic sensor 202 or it could be coupled directly to microfluidic sensor 202, provided that camera 204 is aligned with the first reservoir of microfluidic sensor 202 for colorimetric monitoring of the polymeric matrix.
    [0069] Alternatively, the detection system 200 could be a mobile phone or analogous device, capable of taking photos of the microfluidic device 202, and said image could be subsequently analyzed remotely with the appropriate software; or in situ, if the mobile has the appropriate image analysis program.
    [0070] For the analysis of the captured microfluidic sensor images, the digital image processing module could use software such as ImageJ® or other more complex analytical tools (colorimetric analysis devices, optical fibers, spectrometers, etc.).
    [0071] Figure 4 shows the absorption spectra of the ionogel (black / solid line), of the ionogel after adding copper chloride (blue / striped) and of the ionogel with copper (II) chloride after reacting with ammonia (red / dotted).
    [0072] These spectra have been obtained using UV-VIS-NIR spectrophotometry techniques and correspond to a single microfluidic sensor as described in relation to figure 2. Therefore, the analyzes were performed on the ionogel sample as such, after add copper (II) chloride and after reaction with ammonia. The UV-VIS-NIR spectrum obtained for the microfluidic sensor with only the ionogel shows frequency bands located at 1430, 1615, 1933 and 2260 nm. The UV-VIS-NIR spectrum obtained for the microfluidic sensor with the copper chloride solution shows the maximum absorption of the Cu2 + ion in solution at 415 nm, that is, in the orange and yellow region of the electromagnetic spectrum. After reaction with ammonia and formation of the metal complex, the UV-VIS-NIR spectrum obtained for the microfluidic sensor shows a shift of the main emission band at approximately 615 nm, which corresponds to the maximum absorption of the compound. Cu (NH3) 42+, in the blues region of the electromagnetic spectrum. This is the reason why the human eye perceives the color shift from yellows to blues in the polymer matrix.
    [0073] Said spectra demonstrate the feasibility of detection by visual (human eye) and spectrophotometric techniques to verify the formation of the metal complex [Cu (NH 3 ) 4 ] Ch] that denotes the presence of the analyte of interest.
    [0074] Figure 5A shows an experiment in which four microfluidic sensors are exposed to solutions with different concentrations of ammonium nitrate (through the mortar exudate) and a reference sensor (where no ammonium nitrate is used, only water). Figure 5B shows a histogram showing the mean values of the color parameter "H" detected in the five microfluidic sensors exposed to solutions with different concentrations (0.1 M, 0.3 M) of ammonium nitrate and in a reference microfluidic sensor, obtained using spectrophotometry techniques and ImageJ® software.
    [0075] To carry out this experiment, which is an illustrative example of the operation of the invention that in no case should be interpreted as limiting the scope of protection of the invention, ammonium nitrate was reproduced in the laboratory. This ammonium nitrate (NH 4 NO 3 ) was obtained by mixing ammonium chloride (NH 4 CO and potassium nitrate (KNO 3 ). Three solutions of ammonium chloride and potassium nitrate dissolved in milliQ water at different concentrations (0 , 1 and 0.3 M) In this case the analyte to be detected is ammonia (NH 4 +) after being transformed into ammonia after reacting with the construction material.
    [0076] The solutions were placed inside different plastic containers 300302 capped, and 303 mortar samples supported by metal rods and laboratory clamps (not shown) were placed on top of them. Through a fine opening in the lid, 304 filter paper was used to act as a vehicle between the solutions and the 303 mortar samples. Other samples were exposed to ammonium nitrate vapors to verify if they could detect NH 3 vapors. For the same reason and for reference, a 305 microfluidic sensor was contacted with a water solution only. For the 0.1M NH 4 NO 3 solution, two microfluidic sensors were used, one in the lower part 306 and the other in the upper part 307, simulating two different heights. For the 0.3M NH 4 NO 3 solution, two microfluidic sensors were used, one in the lower part 308 and the other in the upper part 309, simulating the same heights as the microfluidic sensors 306-307.
    [0077] The 306 microfluidic sensor placed on the bottom and exposed to the 0.1M solution showed, after one month, a color change from yellow to light blue. On the other hand, the 307 microfluidic sensor placed in the upper part (13 cm above the other sensor) in the same model 303 did not show evidence of a color change since the solution did not reach, due to capillarity, the sensor inlet hole microfluidic 307 after one month of experiment. Furthermore, the reference microfluidic sensor 305 placed on the bottom of the mockup 303 with the water and filter paper 304 did not show any color change.
    [0078] Thus, the 303 models were placed in a humid place (around 90% humidity) where they remained for about 7 months exposed to the vapors and ammonium nitrate solutions. After 7 months, both 306-307 sensors exposed to the 0.1 M solution showed a clear color change, especially the 306 sensor.
    [0079] The 308-309 microfluidic sensors that were exposed to solutions with higher concentrations (0.3 M) showed a similar chromatic variation, probably due to the long time of the experiment, in which all the sensors could have reached a steady state in the formation. of color.
    [0080] In all cases, due to the high humidity, the presence of water in the second reservoir was observed, proving the viability of this reservoir for the proper functioning of the microfluidic sensor device.
    [0081] Those sensors that have shown a more evident bluish coloration have been those exposed to solutions with higher concentrations of ammonium nitrate, sensors 308-309. To verify these tests by an analytical procedure, an evaluation of the color change in relation to the concentration of the solutions was performed using the open source software ImageJ® (Fiji) created for image processing after taking a picture of the different microfluidic sensors. Thus, the ImageJ® program, using the "Color Transformer" plugin, calculated the HVS values (which is a color model defined in terms of its components, (from the English Hue, Saturation, Value - Hue, Saturation, Value). Subsequently, the areas of interest were selected and then the H value was extracted both from the background (taken in an area of the sensor with the bottom of the model) and from the area of the sensor where the ionogel was located. Thus, the ImageJ® software calculated the H0 value of the background which was subtracted from the H value of the sensor.
    [0082] The values obtained by the graph of the results were compatible with the intensity of the blue color of the sensors after 7 months of exposure to solutions at different concentrations (0.1, 0.3 M and reference), as can be seen in the histogram shown in Figure 5B. The reference value was taken from a photograph taken on a microfluidic sensor before starting the experiment and is the one that shows the highest value of H since no reaction occurred. Low values of H were obtained for the sensors exposed to the 0.1 M solutions, obtaining the lowest values for the sensors exposed to the 0.3 M solutions. In fact, the more intense the color of the sensor (towards blue), the lower the H values.
    [0083] Furthermore, the average value of H was also calculated based on the position of the sensor in the mock-up (lower or higher). The H value was lower in the sensor located in the lower zone of the mortar, sensors 306,308, because it is the sensor closest to the solutions and the one that most detects the presence of ammonia. The same situation was observed for both concentrations (0.1 and 0.3 M). This protocol demonstrated the possibility of using simple image analysis techniques (extracting analytical information from a color change from an image) to characterize the performance of the microfluidic sensor.
    [0084] The invention is not limited to the specific embodiments that have been described, but also encompasses, for example, the variants that can be carried out by the average person skilled in the art within the scope of the claims.
    权利要求:
    Claims (19)
    [1]
    1. A microfluidic sensor for the detection of analytes in an object, characterized in that it comprises:
    a contact surface configured to be coupled to a surface of the object; an inlet hole in the contact surface for the entry of fluids emitted by the surface of the object;
    a first reservoir that stores an ionic fluid in the form of a polymeric matrix, the polymeric matrix comprising a reactive substance that is configured to change color when it comes into contact with at least one analyte present in the fluids emitted by the surface of the object; Y
    at least one first microfluidic conduit connecting the inlet port with the first reservoir.
    [2]
    The microfluidic sensor according to claim 1, wherein the reactive substance is configured to change color by reaction with the at least one analyte in an intensity proportional to the concentration of the analyte.
    [3]
    The microfluidic sensor according to claim 1 or 2, comprising:
    a second reservoir configured to store moisture from the first reservoir; Y
    at least one second microfluidic conduit connecting the first reservoir with the second reservoir.
    [4]
    4. The microfluidic sensor according to any one of the preceding claims, comprising:
    a first pressure sensitive adhesive sheet having a first hole in correspondence with the inlet hole of the microfluidic sensor;
    a polymethylmethacrylate sheet comprising the inlet port, the first reservoir and the at least one first microfluidic conduit;
    a second pressure sensitive adhesive sheet having a second hole in correspondence with the first reservoir; Y
    a cyclic olefin polymer sheet,
    where the first pressure sensitive adhesive sheet adheres to the object and the polymethylmethacrylate sheet and where the second pressure sensitive adhesive sheet adheres to the polymethylmethacrylate sheet and the cyclic olefin polymer sheet.
    [5]
    The microfluidic sensor according to claim 4, wherein the polymethylmethacrylate sheet comprises the second reservoir and the at least one second microfluidic conduit.
    [6]
    6. The microfluidic sensor according to any one of the preceding claims, wherein the analyte is ammonia and the reactive substance is a water-soluble copper (II) salt.
    [7]
    The microfluidic sensor according to claim 6, wherein the water soluble copper salt is copper (II) chloride.
    [8]
    8. The microfluidic sensor according to any one of the preceding claims, wherein the analyte is selected from a group comprising: chlorides, nitrates, carbonates, bicarbonates, sulfates, dissolved cations and any combination of the foregoing.
    [9]
    9. The microfluidic sensor according to any one of the preceding claims, wherein the polymeric matrix is selected from a group comprising an ionogel, a hydrogel, porous polymer, or poly-ionic liquids.
    [10]
    10. The microfluidic sensor according to claim 9, wherein the ionogel is formed by ions selected from a group comprising: thiazole, benzothiazole, phosphonium and imiadazole.
    [11]
    The microfluidic sensor according to any one of the preceding claims, wherein the microfluidic sensor is transparent.
    [12]
    12. The microfluidic sensor according to any one of the preceding claims, wherein the object is a work of art.
    [13]
    13. A system for detecting analytes on an object, comprising:
    a microfluidic sensor according to any one of claims 1 to 12; Y
    a detection unit configured to detect the color change of the reactive substance in the first reservoir of the microfluidic sensor.
    [14]
    14. The analyte detection system according to claim 13 wherein the unit The detection device comprises a camera for monitoring the microfluidic sensor and a digital image processing module for detecting the color change of the reactive substance in the first reservoir of the microfluidic sensor.
    [15]
    The analyte detection system according to claim 13 or 14, wherein the detection unit is selected from a group comprising an ultraviolet-visible spectrometer, an infrared spectrometer and a Raman spectrometer.
    [16]
    16. A method for manufacturing the microfluidic sensor of any one of claims 1 to 12, comprising:
    - providing a contact surface configured to be coupled to a surface of the object;
    - an inlet hole in the contact surface for the entry of fluids emitted by the surface of the object;
    - a first reservoir that stores an ionic fluid, the ionic fluid comprising a reactive substance that is configured to change color when it comes into contact with at least one analyte present in the fluids emitted by the surface of the object; Y
    - at least one first microfluidic conduit connecting the hole with the first reservoir.
    [17]
    17. The method of manufacturing the microfluidic sensor of claim 16, comprising:
    - providing a first pressure sensitive adhesive sheet comprising the contact surface and having a first hole in correspondence with the inlet hole of the microfluidic sensor;
    - providing a polymethylmethacrylate sheet comprising the inlet orifice, the first reservoir and the at least one first microfluidic conduit;
    - providing a second pressure sensitive adhesive sheet having a second hole in correspondence with the first reservoir; Y
    - provide a cyclic olefin polymer sheet,
    where the first pressure sensitive adhesive sheet adheres to the object and the polymethylmethacrylate sheet and where the second pressure sensitive adhesive sheet adheres to the polymethylmethacrylate sheet and the cyclic olefin polymer sheet.
    [18]
    18. Use of the microfluidic sensor of any one of claims 1 to 12 for the detection of analytes in fluids emitted from surfaces of works of art.
    [19]
    19. Use of the microfluidic sensor of any one of claims 1 to 12 for the detection of analytes in fluids emitted from surfaces of building materials.
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    同族专利:
    公开号 | 公开日
    WO2021005254A1|2021-01-14|
    ES2802290B2|2021-05-21|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US20150027906A1|2013-07-24|2015-01-29|Hamilton Sundstrand Corporation|Solid polymer electrolyte ammonia sensor|
    ES2665790A1|2016-10-26|2018-04-27|Universidad Del País Vasco / Euskal Herriko Unibertsitatea|PORTABLE MICROFLUIDIC DEVICE TO DETECT NITRITO-NITRATE |
    CN107830893A|2017-11-02|2018-03-23|厦门大学|A kind of multi-functional microfluid flexible sensor|
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    PCT/ES2020/070433| WO2021005254A1|2019-07-05|2020-07-03|Microfluidic sensor for the detection of analytes|
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