Fluorescence sensor for detecting glucose, preparation method and application

Abstract

The invention provides a fluorescence sensor for detecting glucose, a preparation method and application. Specifically, the fluorescence sensor comprises: a microchannel layer provided with at least one channel and at least one chamber; wherein the chamber is connected with a channel; the upper conversion layer is arranged in the cavity and comprises upper conversion nano particles; the probe layer is arranged on the upper conversion layer and comprises a glucose probe; wherein the exciting light of the up-conversion nanoparticles is near-infrared light, and the emitted light of the up-conversion nanoparticles can excite the glucose probe; the emitted light of the glucose probe is visible light. An upper conversion layer and a probe layer are arranged in the cavity of the micro-channel layer; near-infrared light is adopted to excite up-conversion nano-particles of the up-conversion layer, emitted light of the up-conversion nano-particles is utilized to excite a glucose probe in the probe layer, and the emitted light of the glucose probe is visible light, so that the emitted light can be simply and quickly acquired and analyzed by utilizing a visible light image acquisition device, and a detection result is further obtained.

Description

Technical Field

[0001] The present disclosure relates to the field of detection technologies, and particularly to a fluorescence sensor for detecting glucose, a preparation method thereof, and an application thereof. Background Art

[0002] Diabetes is a chronic disease marked by hyperglycemia, which is caused by absolute or relative insulin deficiency and utilization disorders. As the "gold standard" for diabetes diagnosis, daily blood glucose monitoring is of great significance to both diabetic patients and the normal population.

[0003] At present, most commercially available glucose detection instruments adopt the method of fingertip blood detection, which is also the most widely used and accurate method in clinics and families. However, diabetic patients need to perform blood glucose concentration detection extremely frequently, and collecting fingertip blood will also bring frequent pain and psychological pressure to patients, and there is also a risk of wound infection. Summary of the Invention

[0004] In view of this, the purpose of the present disclosure is to provide a fluorescence sensor for detecting glucose, a preparation method thereof, and an application thereof.

[0005] Based on the above purpose, the present disclosure provides a fluorescence sensor for detecting glucose, and the fluorescence sensor includes:

[0006] A microchannel layer, provided with at least one channel and at least one chamber; wherein, the chamber is connected to the channel;

[0007] An upconversion layer, disposed in the chamber, including upconversion nanoparticles; and

[0008] A probe layer, disposed on the upconversion layer, including a glucose probe; wherein,

[0009] The excitation light of the upconversion nanoparticles is near-infrared light and its emission light can excite the glucose probe; the emission light of the glucose probe is visible light.

[0010] In some embodiments, the upconversion layer further includes a first matrix; the probe layer further includes a second matrix, and the first matrix and the second matrix are not mutually soluble with each other.

[0011] In some embodiments, the upconversion nanoparticles are NaYF4:Yb,Tm@NaYF4; and / or

[0012] The glucose probe includes a fluorescent pyrene-based polymer organic framework.

[0013] In some embodiments, the fluorescent pyrene-based polymer organic framework includes 4-formylphenylboronic acid.

[0014] In some embodiments, the building units of the fluorescent pyrene-based polymer organic framework include melamine, aromatic dialdehyde, 1-pyrenecarboxaldehyde, and 4-formylphenylboronic acid.

[0015] In some embodiments, the first matrix is polymethyl methacrylate; and / or, the second matrix is polyurethane.

[0016] In some embodiments, the diameter of the chamber is 2 - 3 mm, and the height is 80 - 120 μm.

[0017] In some embodiments, the microchannel layer includes a body layer and a cover plate.

[0018] Based on the same inventive concept, embodiments of the present disclosure also provide an application of any of the foregoing fluorescent sensors in the detection of sweat glucose.

[0019] Based on the same inventive concept, embodiments of the present disclosure also provide a preparation method of a fluorescent sensor for detecting glucose, including:

[0020] Providing a body layer including at least one channel and at least one chamber;

[0021] Forming an upconversion layer and a probe layer in the chamber;

[0022] Providing a cover plate and bonding the body layer and the cover plate; wherein,

[0023] The upconversion layer includes upconversion nanoparticles; the probe layer includes a glucose probe; the excitation light of the upconversion nanoparticles is near-infrared light and its emission light can excite the glucose probe, and the emission light of the glucose probe is visible light.

[0024] As can be seen from the above, a fluorescent sensor for detecting glucose, a preparation method, and an application provided by the present disclosure set an upconversion layer and a probe layer in the chamber of the microchannel layer; use near-infrared light to excite the upconversion nanoparticles in the upconversion layer, and use the emission light of the upconversion nanoparticles to excite the glucose probe in the probe layer. The emission light of the glucose probe is visible light, so that the emission light can be simply and quickly collected and analyzed by a visible light image acquisition device, and then the detection result can be obtained. Description of the Drawings

[0025] In order to more clearly illustrate the technical solutions in the present disclosure or related technologies, the following will briefly introduce the drawings required for use in the description of the embodiments or related technologies. Obviously, the drawings in the following description are only embodiments of the present disclosure. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0026] Figure 1Schematic structural diagram of a fluorescence sensor for detecting glucose provided by an embodiment of the present disclosure;

[0027] Figure 2 Schematic preparation process diagram of a fluorescence sensor for detecting glucose provided by an embodiment of the present disclosure;

[0028] Figure 3 Photo of a NaYF4:Yb,Tm@NaYF4 transmission electron microscope provided by an embodiment of the present disclosure;

[0029] Figure 4 Schematic structural diagram of a glucose probe provided by an embodiment of the present disclosure;

[0030] Figure 5 Schematic diagram of the fluorescence emission spectrum of a glucose probe at different glucose concentrations provided by an embodiment of the present disclosure;

[0031] Figure 6 Fitting curve of the emission peak intensity at 472 nm of the film layer of a sensor at different glucose concentrations provided by an embodiment of the present disclosure;

[0032] Figure 7 Fluorescence signal change of a sensor at different glucose concentrations under 980 nm excitation provided by an embodiment of the present disclosure;

[0033] Figure 8 Stability test results of a sensor within 20 days of storage provided by an embodiment of the present disclosure. Detailed implementation manners

[0034] To make the objectives, technical solutions, and advantages of the present disclosure clearer and more understandable, the following further elaborates on the present disclosure in detail with reference to specific embodiments and the accompanying drawings.

[0035] It should be noted that unless otherwise defined, the technical terms or scientific terms used in the embodiments of the present disclosure should have the ordinary meanings understood by those with ordinary skills in the field to which the present disclosure belongs. The terms "first", "second", and similar terms used in the embodiments of the present disclosure do not indicate any order, quantity, or importance, but are only used to distinguish different components. Terms such as "including" or "comprising" can be open, semi-closed, and closed. In other words, these terms also include "substantially consisting of...", or "consisting of...". Terms such as "connected" or "coupled" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. Terms such as "upper", "lower", "left", "right", etc. are only used to represent relative positional relationships, and when the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0036] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods, which are carried out according to the techniques or conditions described in the literature in this field or according to the product specifications.

[0037] Unless otherwise specified, "μM" in this article refers to "μmol / L", and "mM" refers to "mmol / L".

[0038] As described in the background art section, diabetic patients need to perform blood glucose concentration detection extremely frequently. Pricking the fingertip for blood will also bring frequent pain and psychological pressure to the patients, and there is also a risk of wound infection. Considering that the glucose concentration in sweat has a great correlation with the glucose concentration in blood, evaluating the blood glucose index of the human body by detecting the glucose concentration in solutions such as sweat is a potential blood glucose concentration detection method.

[0039] Bio-detection technologies based on optical analysis are often applied to the field of glucose detection because of their advantages such as fast speed, high sensitivity, real-time, high-frequency monitoring, and low cost. An optical sensor usually consists of an optical probe and a matrix material, and is realized by analyzing the specific optical signal change after the optical probe acts on the analyte. In the related technologies, most of the optical sensors for detecting glucose in sweat use short-wave excitation, which inevitably generates autofluorescence with sweat or chip materials, thus generating strong background fluorescence.

[0040] In view of this, the embodiments of the present disclosure provide a fluorescence sensor for detecting glucose, a preparation method and an application thereof. An upconversion layer and a probe layer are arranged in the chamber of the microchannel layer; the upconversion nanoparticles in the upconversion layer are excited by near-infrared light, and the emission light of the upconversion nanoparticles is used to excite the glucose probe in the probe layer. The emission light of the glucose probe is visible light, so that the emission light can be simply and quickly collected and analyzed by a visible light image acquisition device, and then the detection result can be obtained. With such a technical solution, excitation by a near-infrared light source can avoid the generation of autofluorescence, thereby reducing errors, improving detection accuracy, and expanding the detection range.

[0041] Figure 1 It is a schematic structural diagram of a fluorescence sensor for detecting glucose provided by the embodiments of the present disclosure. As Figure 1 shown, the fluorescence sensor includes a microchannel layer 101, an upconversion layer 102, and a probe layer 103. The size of the fluorescence sensor can be flexibly set according to needs. For example, it is 5 cm long, 4 cm wide, and 3 mm high. The present disclosure does not limit this.

[0042] It should be noted that the microchannel layer 101 is an important component of the microfluidic chip. With the help of the microchannel layer 101, liquids with a small volume can be processed, mixed, transported, and analyzed, etc., featuring high throughput, speed, efficiency, and automation. For the fluorescence sensor provided in the embodiments of the present disclosure, the liquid with a small volume can be blood, saliva, sweat, etc., and the present disclosure does not limit this. Comparatively, the liquid with a small volume is not only more convenient to collect, but also imposes a smaller burden on diabetic patients.

[0043] In some embodiments, the microchannel layer 101 includes at least one channel 1012 and at least one chamber 1013; wherein, the chamber 1013 is connected to the channel 1012. As Figure 1 shown, the number of channels 1012 is 2, and each channel 1012 is connected to 4 chambers 1013. Here, the channel 1012 can guide the liquid to be measured into the chamber 1013, thereby facilitating the detection of the liquid to be measured in the chamber 1013.

[0044] Optionally, the microchannel layer 101 includes a body layer 1011 and a cover plate 1014. It should be noted that the manner of the body layer 1011 and the cover plate 1014 has advantages such as convenient preparation and low processing difficulty.

[0045] Exemplarily, the channel 1012 and the chamber 1013 can be formed on the body layer 1011 (as Figure 1 shown), at this time, the cover plate 1014 serves to enclose the channel 1012 and the chamber 1013. Of course, the channel 1012 and the chamber 1013 can be divided in the height direction, with part formed on the body layer 1011 and part formed on the cover plate 1014. After the body layer 1011 and the cover plate 1014 are bonded, a complete channel 1012 and chamber 1013 are formed, and the present disclosure does not limit this.

[0046] Optionally, the diameter of the chamber 1013 is 2.0 - 3.0 mm, such as 2.0 mm, 2.2 mm, 2.5 mm, 2.8 mm, 3.0 mm; and the height is 80 - 120 μm, such as 80 μm, 90 μm, 100 μm, 110 μm, 120 μm.

[0047] In some embodiments, the upconversion layer 102 and the probe layer 103 are disposed in the chamber 1013, wherein, the probe layer 103 is located on the upconversion layer 102, for example, on the side of the upconversion layer 102 away from the body layer 1011. Here, an optical signal can be transmitted between the upconversion layer 102 and the probe layer 103. Specifically, the emitted light of the upconversion layer 102 can enter the probe layer 103 to realize the excitation of the probe layer 103.

[0048] In some embodiments, the upconversion layer 102 includes upconversion nanoparticles and a first matrix; the probe layer 103 includes a glucose probe and a second matrix. The upconversion nanoparticles and the glucose probe are respectively located in the upconversion layer 102 and the probe layer 103, which effectively avoids fluorescence quenching caused by direct contact between the two, and can ensure that the glucose probe is effectively excited. Furthermore, the excitation light of the upconversion nanoparticles is near-infrared light (e.g., 980nm) and its emission light can excite the glucose probe; the emission light of the glucose probe is visible light. Based on this, after injecting glucose solutions of different concentrations into the sensor, near-infrared light excitation is used, and an imaging picture is obtained through an image acquisition device (e.g., a mobile phone). By analyzing the red, green, and blue (RGB) grayscale values ​​in the picture, real-time and accurate detection of the glucose concentration in the solution can be achieved.

[0049] Figure 3 This is a transmission electron microscope photo of NaYF4:Yb,Tm@NaYF4 provided in the embodiment of the present disclosure. Figure 3 As shown, the upconversion nanoparticles are NaYF4:Yb,Tm@NaYF4. Figure 4 Schematic diagram of the structure of a glucose probe provided by an embodiment of the present disclosure. Figure 4 As shown, the glucose probe includes a fluorescent pyrene-based polymer organic framework. Under a suitable chemical environment, when the glucose probe contacts the glucose molecule, the emission peak at 472nm is quenched, so that the glucose concentration in the solution can be analyzed by the emission peak intensity at 472nm, and sensitive detection of glucose in the aqueous solution is achieved. Further, the fluorescent pyrene-based polymer organic framework includes 4-formylphenylboronic acid (4-FPBA). 4-formylphenylboronic acid (4-FPBA) has high chemical stability, high quantum yield and long fluorescence lifetime. When in contact with glucose molecules, the excimer gradually changes to a monomer, the monomer peak intensity is enhanced, and the excimer undergoes fluorescence quenching, which is macroscopically manifested as fluorescence quenching at 472nm. This change in fluorescence intensity can be captured by an image acquisition device (such as a mobile phone camera) to obtain a corresponding image, and then the image RGB grayscale value can be analyzed to obtain the sweat glucose concentration.

[0050] It should be noted that the building blocks of the fluorescent pyrene-based polymer organic framework include melamine, aromatic dialdehyde, 1-pyrene formaldehyde and 4-formylphenylboronic acid.

[0051] When using 980nm near-infrared excitation, the rare earth ion Tm 3+ of 1 D2 layer electrons 3 The H6 layer transition produces purple light of about 360nm, which has good luminescence linearity, narrow emission peak, and coincides with the excitation peak of the selected probe, making it suitable for exciting the glucose probe.

[0052] In some embodiments, the first matrix and the second matrix are immiscible with each other. Exemplarily, the first matrix is an oil-soluble solvent such as polystyrene, polymethyl methacrylate (PMMA), and polycarbonate; the second matrix is a water-soluble solvent such as polyvinyl alcohol, polyvinylpyrrolidone, chitosan, and polyurethane. The immiscibility of the first matrix and the second matrix helps to completely separate the upconversion nanoparticles and the glucose probe, avoiding fluorescence quenching.

[0053] Figure 2 Schematic diagram of the preparation process of a fluorescence sensor for detecting glucose provided by an embodiment of the present disclosure. As Figure 2 shown, the preparation method includes:

[0054] First, provide a body layer 1011 including at least one channel and at least one chamber 1013 and a cover plate 1014. For the formation steps of the body layer 1011 and the cover plate 1014, the following is an exemplary description:

[0055] Refer to Figure 2 , for the body layer 1011, provide a substrate 201 (such as a silicon wafer, glass, etc.), and use photoresist to engrave the channel and cavity shapes on the substrate to obtain a silicon-based positive film. Exemplarily, apply photoresist (such as SU-8 2050) on the substrate, and use a mask to form a photoresist layer 202 with channel and cavity shapes under the conditions of exposure (such as 365 nm ultraviolet light) and development. Pour polydimethylsiloxane 203 (PDMS) on the photoresist layer 202, and after thermal curing, peel off the photoresist layer 202 to obtain the body layer 1011. For the cover plate 1014, compared with the body layer 1011, the mask and the photoresist layer can be omitted; pour polydimethylsiloxane 203 (PDMS) on a smooth surface (such as the substrate 201), and after thermal curing and peeling, the cover plate 1014 can be obtained. It should be understood that if grooves corresponding to the channels and cavities are provided on the cover plate 1014, the same preparation method as that of the body layer 1011 can be adopted, which will not be elaborated here.

[0056] Next, form an upconversion layer 102 and a probe layer 103 in the chamber 1013.

[0057] The upconversion layer 102 includes upconversion nanoparticles; the probe layer 103 includes a glucose probe.

[0058] Taking the upconversion nanoparticles as NaYF4:Yb,Tm@NaYF4; the glucose probe includes a fluorescent pyrene-based polymer organic framework as an example, the preparation methods of the upconversion layer 102 and the probe layer 103 are exemplarily described. Here, the excitation light of the upconversion nanoparticles is near-infrared light and its emission light can excite the glucose probe, and the emission light of the glucose probe is visible light.

[0059] Prepare a cyclohexane solution of NaYF4:Yb,Tm using trifluoroacetate, oleic acid, octadecene, etc.; prepare a cyclohexane solution of NaYF4:Yb,Tm@NaYF4 using the cyclohexane solution of NaYF4:Yb,Tm, trifluoroacetate, oleic acid, and octadecene; mix the cyclohexane solution of NaYF4:Yb,Tm@NaYF4 and the toluene solution of polymethyl methacrylate, and drop it into chamber 1013, and dry it to form the upconversion layer 102.

[0060] Using melamine, aromatic dialdehyde, 1-pyrenecarboxaldehyde, and 4-formylphenylboronic acid (4-FPBA) as building units, fluorescent pyrene-based polymer organic frameworks (POFs) PY-POFs are synthesized by a solvothermal method; mix it evenly with a polyurethane hydrogel, drop it on the upconversion layer 102, and dry it to obtain the probe layer 103. Here, the ratio of PY-POFs to the polyurethane hydrogel is 1:5 to 5:1, such as 1:1.

[0061] Finally, bond the main body layer 1011 and the cover plate 1014. It should be noted that the present disclosure does not limit the bonding method, such as oxygen plasma cleaning and punching bonding.

[0062] The embodiment of the present disclosure also provides the application of the above fluorescence sensor in the detection of sweat glucose. Exemplarily, injecting sweat into the above fluorescence sensor and analyzing the blue grayscale value by taking pictures can determine the glucose concentration in the sweat, thereby realizing the detection of sweat glucose.

[0063] In order to make the technical solutions of the present disclosure clearer and easier to understand, the following will combine the drawings and specific embodiments to detail a fluorescence sensor for detecting glucose, a preparation method, and an application provided by the present disclosure.

[0064] Example 1

[0065] (1) Preparation of NaYF4:Yb,Tm:

[0066] First, prepare 1 mmol of rare earth element trifluoroacetates, including 79.5% of Y(CF3COO)3, 20% of Yb(CF3COO)3, and 0.5% of Tm(CF3COO)3. Then, measure 5.64 g of oleic acid and 5.04 g of octadecene, mix them with the above-mentioned rare earth element trifluoroacetates, and add them to a 100 mL three-necked flask. Heat the mixture to 120 °C and stir until completely dissolved to obtain a light yellow clear mixed solution. Stir for 30 min, then evacuate the mixed solution at 120 °C for 30 min. Under nitrogen protection, heat the solution to 315 °C and maintain this temperature for 90 min. Subsequently, cool the solution to room temperature. Add 5 ml of absolute ethanol, ultrasonically vibrate for 5 min, and centrifuge at a speed of 10000 r / min for 10 min. After centrifugation, disperse the precipitate at the bottom of the centrifuge tube into 10 ml of cyclohexane and ultrasonically vibrate for 10 min to obtain a NaYF4:Yb,Tm cyclohexane solution.

[0067] (2) Preparation of NaYF4:Yb,Tm@NaYF4:

[0068] Prepare 0.214 g of Y(CF3COO)3, 0.136 g of Na(CF3COO)3, 5.64 g of oleic acid, 5.04 g of octadecene, and 5 ml of NaYF4:Yb,Tm cyclohexane solution. Evacuate the mixed solution at 120 °C for 30 min. Under nitrogen protection, heat the solution to 315 °C and maintain this temperature for 90 min. Then, cool the solution to room temperature. Add 5 ml of absolute ethanol, ultrasonically vibrate for 5 min, and centrifuge at a speed of 10000 r / min for 10 min. After centrifugation, disperse the precipitate at the bottom of the centrifuge tube into 10 mL of cyclohexane and ultrasonically vibrate for 10 min to obtain a NaYF4:Yb,Tm@NaYF4 cyclohexane solution.

[0069] (3) Preparation of glucose probe PY-POFs:

[0070] Dissolve melamine (MA) (2 mmol) and aromatic dialdehyde (TA) (3 mmol) in 15 mL of DMSO and stir at 45 °C for about 30 min to obtain a clear solution. After 30 min, add 1-pyrenecarboxaldehyde (1-PCA) (1 mmol) and 4-formylphenylboronic acid (4-FPBA) (1 mmol) to the above solution and stir again at 45 °C for about 30 min to obtain a clear solution. Then transfer the solution to a Teflon-lined autoclave and heat at 180 °C for 16 h. After the reaction is completed, cool the autoclave to room temperature, collect the obtained highly fluorescent light yellow precipitate, and then wash it with excess water, acetone, and dichloromethane. The collected precipitate is heated at 80 °C under dynamic vacuum for 24 h.

[0071] (4) Preparation of the body layer 1011 and the cover plate 1014:

[0072] The body layer 1011 and the cover plate 1014 are prepared by the foregoing method, which will not be elaborated here.

[0073] (5) Preparation of the upconversion layer 102 and the probe layer 103:

[0074] Mix the near-infrared upconversion nanoparticles obtained in step (2) with a toluene solution of PMMA, and drop 2 μl into each chamber of the chip. After drying, an upconversion thin film is formed, which is the upconversion layer; mix the PY-POFs probe in step (3) with 20 wt% polyurethane hydrogel in a volume ratio of 1:1 evenly, and drop 5 μl into each chamber of the chip and dry to obtain a glucose-sensitive film, which is the probe layer.

[0075] (6) Bond the body layer 1011 and the cover plate 1014

[0076] Bond the body layer 1011 integrated with the double-layer film and the cover plate 1014 using an oxygen plasma cleaner. After completion, place it in an oven at 60 °C for 2 hours to stabilize the sensor structure, and thus the fluorescence sensor is obtained.

[0077] Example 2

[0078] The difference between this example and Example 1 is only that the PY-POFs probe is mixed with polyurethane hydrogel at a ratio of 5:1.

[0079] Example 3

[0080] The difference between this example and Example 1 is only that the PY-POFs probe is mixed with polyurethane hydrogel at a ratio of 1:5.

[0081] Next, the performance of the fluorescence sensor is studied.

[0082] Research on the Glucose-Sensitive Characteristics of the Sensor

[0083] The spectral characterization of the glucose-sensitive characteristics of the sensor is measured by a spectrometer model F4600 produced by Hitachi. The sample cell used for spectral characterization is a four-side light-transmitting quartz cuvette of 1.0 cm × 1.0 cm. Use a laser with a wavelength of 365 nm to excite the sensing thin film, and detect the change in the fluorescence emission intensity of the sensing thin film with the concentration of the glucose solution. Here, the sensing thin film is obtained by mixing the PY-POFs prepared in step (3) of Example 1 with 20 wt% polyurethane hydrogel evenly and drying.

[0084] Add glucose solutions with different concentrations (2, 4, 6, 8, 10, 15, 20 mM) to the cuvette containing the sensing film. After sufficient reaction, characterize the emission spectra of the sensing film added with glucose solutions with different concentrations by a fluorescence spectrometer. The excitation wavelength is 365 nm, and the monitoring wavelength is 420 - 600 nm. The results are asFigure 5 As shown in Figure 5 It can be seen that when the glucose concentration increases from 2 mM to 20 mM, the luminescence intensity of the probe gradually decreases as the glucose concentration increases.

[0085] Figure 6 This is the fitting curve of the emission peak intensity at 472 nm of the film layer of a sensor provided by an embodiment of the present disclosure under different glucose concentrations. As can be seen from Figure 6 It can be seen that as the glucose concentration increases, the emission light intensity of the sensing film gradually decreases. After normalizing each peak value (I) by the initial intensity (I0), the fluorescence intensity of the sensing film shows a good linear relationship with the glucose concentration, and the fitting degree reaches 0.9814, indicating that the sensing film shows high sensitivity to the glucose concentration.

[0086] Thus, it can be seen that the glucose sensing film shows high glucose sensitivity and resolution.

[0087] Research on the Imaging Performance of the Sensor

[0088] The imaging performance of the sensor is obtained by exciting the sensor prepared in Example 1 with a 980 nm laser, slowly injecting glucose solutions with different concentrations (2, 4, 6, 8, 10, 15, 20 mM) into the sensor, taking pictures with a mobile phone, and analyzing the gray value of the blue (B) channel of the picture through software.

[0089] Analyzing the imaging test results of the sensor for different concentrations of glucose, as Figure 7 shown, as the glucose concentration continuously increases, the gray value of the B channel of the imaging picture gradually weakens, showing high glucose sensitivity and reversibility of the sensor. Based on the corresponding relationship between the gray value and the glucose concentration, by analyzing the gray value of the blue channel obtained by taking pictures, the glucose concentration can be matched.

[0090] Research on the Stability of the Sensor

[0091] The stability of the sensor is measured by analyzing the imaging data taken by the mobile phone. The fabricated sensor is stored for 20 days under dry and light-proof conditions. During this period, the sensor is excited with the same 980 nm light source to obtain imaging results. As Figure 8 shown, the luminescence intensity of the sensor does not change significantly during the detection period, indicating that the sensing film matrix has a good protective effect on the glucose probe and the sensor has good stability.

[0092] It should be noted that the sensors prepared in Example 2 and Example 3 have similar effects and will not be elaborated here.

[0093] In summary, the sensor provided by the embodiments of the present disclosure is excited by a 980 nm near-infrared laser, has low background noise, high sensitivity, and a large detection range; the sensor can achieve in-situ direct detection of glucose in solution; the sensor material is stable and can achieve multiple repeated detections; by using an image acquisition device to take pictures and analyzing the pictures, the detection results can be obtained, which has the advantages of simplicity and rapidity; in short, it has outstanding advantages in the applications in the fields of glucose detection and related disease diagnosis and treatment, etc., showing good application prospects.

[0094] Those of ordinary skill in the art should understand that the discussion of any embodiment above is only exemplary, and is not intended to imply that the scope of the present disclosure (including the claims) is limited to these examples; under the concept of the present disclosure, the technical features in the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations in different aspects of the embodiments of the present disclosure as described above, which are not provided in detail for the sake of brevity.

[0095] The embodiments of the present disclosure are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omission, modification, equivalent substitution, improvement, etc. made within the spirit and principle of the embodiments of the present disclosure shall be included within the protection scope of the present disclosure.

Claims

1. A fluorescence sensor for detecting glucose, characterized in that, The fluorescence sensor includes: a microchannel layer provided with at least one channel and at least one chamber; wherein the chamber is connected to the channel; a upconversion layer disposed in the chamber and including upconversion nanoparticles; and a probe layer disposed on the upconversion layer and including a glucose probe; wherein the excitation light of the upconversion nanoparticles is near-infrared light and its emission light can excite the glucose probe; the emission light of the glucose probe is visible light.

2. The fluorescence sensor according to claim 1, characterized in that, The upconversion layer further includes a first matrix; the probe layer further includes a second matrix, and the first matrix and the second matrix are immiscible with each other.

3. The fluorescence sensor according to claim 1, wherein The upconversion nanoparticles are NaYF4:Yb,Tm@NaYF4; and / or the glucose probe includes a fluorescent pyrene-based polymer organic framework.

4. The fluorescence sensor according to claim 3, wherein The fluorescent pyrene-based polymer organic framework includes 4-formylphenylboronic acid.

5. The fluorescence sensor according to claim 3, characterized in that, The building units of the fluorescent pyrene-based polymer organic framework include melamine, aromatic dialdehyde, 1-pyrenecarboxaldehyde and 4-formylphenylboronic acid.

6. The fluorescence sensor according to claim 2, wherein The first matrix is polymethyl methacrylate; and / or, the second matrix is polyurethane.

7. The fluorescence sensor according to claim 1, wherein The diameter of the chamber is 2-3 mm and the height is 80-120 μm.

8. The fluorescence sensor according to claim 1, characterized in that, The microchannel layer includes a body layer and a cover plate.

9. Use of the fluorescence sensor according to any one of claims 1 to 8 in the detection of sweat glucose.

10. A method for preparing a fluorescence sensor for detecting glucose, characterized in that, Including: providing a body layer including at least one channel and at least one chamber; forming an upconversion layer and a probe layer in the chamber; providing a cover plate and bonding the body layer and the cover plate; wherein the upconversion layer includes upconversion nanoparticles; the probe layer includes a glucose probe; the excitation light of the upconversion nanoparticles is near-infrared light and its emission light can excite the glucose probe, and the emission light of the glucose probe is visible light.

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