Breathing valve for mask, expired air condensate collecting mask and application and detection method of breathing valve and expired air condensate collecting mask

Abstract

The invention provides a breather valve for a mask, an exhaled air condensate collecting mask and application and detection methods of the breather valve and the exhaled air condensate collecting mask, and the breather valve for the mask comprises a breather valve body which comprises an air inlet; the collecting piece is arranged in the breather valve body and is used for collecting exhaled air condensate; the collecting piece comprises a patterned gold nanoparticle superlattice film, and the patterned gold nanoparticle superlattice film is arranged towards the air inlet. The breathing valve for the mask contains the patterned gold nanoparticle superlattice film, expired air condensate is directionally evaporated and shrunk on the surface of the breathing valve, and therefore uniform and concentrated distribution of analytes is achieved. The purpose of accurately detecting exhaled air condensate is achieved through Raman spectrum, and the detection sensitivity is high. Moreover, the mask comprising the breather valve for the mask is convenient to carry, low in manufacturing cost and suitable for wide application.

Description

Technical Field

[0001] The present application relates to the field of materials, and in particular to a breathing valve for a mask and an exhaled breath condensate collection mask, and applications and detection methods thereof. Background Art

[0002] Exhaled breath condensate contains many biochemical components related to health. The traditional method is to use condensation equipment to collect exhaled breath condensate and test the collected samples with analytical instruments. This method has the problems of expensive condensation devices, lack of portability, complex structure, and inability to accurately control the distribution of analytes, making it difficult to widely promote the detection of exhaled breath condensate. Summary of the invention

[0003] The present application aims to solve the technical problems existing in the prior art at least to a certain extent. To this end, the present application proposes a breathing valve for a mask and a mask for collecting exhaled breath condensate and its application and detection method. The breathing valve for a mask contains a patterned gold nanoparticle superlattice film, and the exhaled breath condensate will evaporate and shrink in a direction on its surface, thereby achieving a uniform and concentrated distribution of the analyte. The purpose of accurately detecting the exhaled breath condensate is achieved by Raman spectroscopy, and the detection sensitivity is high. In addition, the mask containing the breathing valve for a mask of the present application is easy to carry, has a low production cost, and is suitable for wide application.

[0004] In one aspect of the present application, the present application proposes a breathing valve for a mask. According to an embodiment of the present application, the breathing valve for a mask comprises: a breathing valve body, the breathing valve body comprising an air inlet; a collecting member, the collecting member being arranged in the breathing valve body and used to collect exhaled air condensate; the collecting member comprising a patterned gold nanoparticle superlattice film, the patterned gold nanoparticle superlattice film being arranged toward the air inlet.

[0005] According to the embodiment of the present application, the breathing valve for the mask contains a patterned gold nanoparticle superlattice film, and the exhaled breath condensate will evaporate and shrink in a directional manner on its surface, thereby achieving uniform and concentrated distribution of the analyte. The purpose of accurately detecting the exhaled breath condensate is achieved through Raman spectroscopy, with high detection sensitivity and suitable for wide application.

[0006] According to an embodiment of the present application, the breathing valve for a mask may also have the following additional technical features:

[0007] According to an embodiment of the present application, the collecting element includes: a substrate; a plurality of gold nanoparticle superlattice domains, wherein the plurality of gold nanoparticle superlattice domains are spaced apart on a surface of the substrate facing the air inlet, each of the gold nanoparticle superlattice domains comprising a plurality of tightly packed gold nanoparticles, and the plurality of gold nanoparticle superlattice domains form the patterned gold nanoparticle superlattice film.

[0008] According to an embodiment of the present application, the surface of the substrate facing the gold nanoparticle superlattice domain is modified with trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane; and the surface of the gold nanoparticle superlattice domain has oleylamine molecules.

[0009] According to an embodiment of the present application, the contact angle of the substrate is 100° to 110°, and the contact angle of the gold nanoparticle superlattice domain is 10° to 60°; the surface of the gold nanoparticle superlattice domain has modified molecules, and the modified molecules are suitable for reacting with the analyte to be measured and generating Raman signal changes.

[0010] According to an embodiment of the present application, the material of the substrate includes silicon or polydimethylsiloxane.

[0011] According to an embodiment of the present application, the shortest spacing distance between two adjacent gold nanoparticle superlattice domains is 200 μm to 250 μm.

[0012] According to an embodiment of the present application, the collecting piece is detachably disposed in the mask breathing valve body.

[0013] In another aspect of the present application, the present application proposes an exhaled breath condensate collection mask. According to an embodiment of the present application, the exhaled breath condensate collection mask comprises a mask body, a breathing area is formed on the inner side of the mask body; the aforementioned mask breathing valve, the patterned gold nanoparticle superlattice film is connected to the breathing area.

[0014] In another aspect of the present application, the present application proposes the use of the above-mentioned breathing valve for masks or the exhaled breath condensate collection mask in the preparation of detection products. According to an embodiment of the present application, the detection product is used to detect exhaled breath condensate.

[0015] In another aspect of the present application, the present application proposes a method for detecting exhaled breath condensate for non-diagnostic purposes. According to an embodiment of the present application, the method comprises: having a subject wear the exhaled breath condensate collection mask described above and breathe so as to form exhaled breath condensate droplets on the patterned gold nanoparticle superlattice film; and performing Raman spectroscopy detection on the patterned gold nanoparticle superlattice film after drying the exhaled breath condensate.

[0016] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0018] Figure 1 A schematic diagram and actual photos of a portable exhaled breath condensate collection mask constructed in Example 1 of the present application are shown;

[0019] Figure 2 Optical microscope and scanning electron microscope characterization images of the patterned gold nanoparticle superlattice film prepared in Example 1 of the present application are shown;

[0020] Figure 3 A schematic diagram showing the collection of analytes in exhaled breath condensate droplets by the patterned gold nanoparticle superlattice membrane prepared in Example 1 of the present application;

[0021] Figure 4 The Raman signals of the exhaled breath condensate of a healthy person and a cold patient in Example 1 of the present application are shown;

[0022] Figure 5 shows the Raman signal measured on the surface of the patterned gold nanoparticle superlattice film of Example 2 of the present application;

[0023] Figure 6 The Raman signal intensity of hydrogen peroxide detected at different concentrations in Example 2 of the present application and the linear calibration curve of hydrogen peroxide are shown;

[0024] Figure 7 The Raman signals of different application scenarios of Example 3 of the present application are shown. DETAILED DESCRIPTION

[0025] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be understood as limiting the present invention.

[0026] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. Further, in the description of the present invention, unless otherwise specified, the meaning of "plurality" is two or more.

[0027] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0028] In this document, the terms “include” or “comprising” are open expressions, that is, including the contents specified in the present invention but not excluding other contents.

[0029] The present application proposes a breathing valve for a mask, an exhaled breath condensate collection mask, and its application in the preparation of a detection product and a method for detecting exhaled breath condensate, which will be described in detail below.

[0030] Breathing valve for mask

[0031] In one aspect of the present application, the present application proposes a breathing valve for a mask. According to an embodiment of the present application, the breathing valve for a mask comprises: a breathing valve body, the breathing valve body comprising an air inlet; a collecting member, the collecting member being arranged in the breathing valve body and used to collect exhaled air condensate; the collecting member comprising a patterned gold nanoparticle superlattice film, the patterned gold nanoparticle superlattice film being arranged toward the air inlet.

[0032] According to the embodiment of the present application, the breathing valve for the mask contains a patterned gold nanoparticle superlattice film, and the exhaled breath condensate will evaporate and shrink in a directional manner on its surface, thereby achieving uniform and concentrated distribution of the analyte, overcoming the problem that the traditional device cannot accurately control the distribution of the analyte. The purpose of accurately detecting the exhaled breath condensate is achieved through Raman spectroscopy, with high detection sensitivity and suitable for wide application.

[0033] In this application, the term "patterned gold nanoparticle superlattice film" is an ordered arrangement structure formed by gold nanoparticles through self-assembly or external field induction. In this film, gold nanoparticles are arranged in a periodic manner as basic units to form a patterned film material with macroscopic size. This structure not only retains the optical, electrical and catalytic properties of gold nanoparticles, but also exhibits unique physical and chemical properties through the interaction and arrangement between particles, such as enhanced surface plasmon resonance effect and excellent surface enhanced Raman scattering (SERS) performance.

[0034] According to an embodiment of the present application, the collecting element includes: a substrate; a plurality of gold nanoparticle superlattice domains, wherein the plurality of gold nanoparticle superlattice domains are spaced apart on a surface of the substrate facing the air inlet, each of the gold nanoparticle superlattice domains comprising a plurality of tightly packed gold nanoparticles, and the plurality of gold nanoparticle superlattice domains form the patterned gold nanoparticle superlattice film.

[0035] The small domain contained by the tightly packed gold nanoparticles is called a gold nanoparticle superlattice domain, that is, a membrane area. The membrane area (small domain) is repeated periodically on the substrate as a basic unit to form a patterned gold nanoparticle superlattice film. Compared with the detection of a single gold nanoparticle superlattice domain for collection, which is more accidental, multiple gold nanoparticle superlattice domains can be used for detection to take the average value through multiple tests to improve the accuracy of the detection. Therefore, the construction of multiple gold nanoparticle superlattice domains is very necessary, that is, the gold nanoparticle superlattice domains need to be set at intervals.

[0036] In some embodiments, a patterned gold nanoparticle superlattice film can be formed on a substrate by inkjet printing.

[0037] According to an embodiment of the present application, the surface of the substrate facing the gold nanoparticle superlattice domain is modified with trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane; and the surface of the gold nanoparticle superlattice domain has oleylamine molecules.

[0038] The surface of the substrate modified with trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane is hydrophobic, and the gold nanoparticle superlattice domain with oleylamine molecules is hydrophilic, which realizes the regulation of the surface wettability of the substrate and the gold nanoparticle superlattice domain. The exhaled breath condensate droplets tend to evaporate and shrink in the hydrophilic area, so the analyte can be evenly and concentratedly distributed in the gold nanoparticle superlattice domain. According to an embodiment of the present application, the contact angle of the substrate is 100° to 110°, for example, 100°, 102°, 104°, 105°, 106°, 108°, 110°, and the contact angle of the gold nanoparticle superlattice domain is 10° to 60°, for example, 10°, 20°, 30°, 40°, 50°, 60°. Thus, the regulation of the surface wettability of the substrate and the gold nanoparticle superlattice domain can be achieved. The exhaled breath condensate droplets tend to evaporate and shrink toward the hydrophilic area, so the analytes can be evenly and concentratedly distributed in the gold nanoparticle superlattice domain.

[0039] According to an embodiment of the present application, the surface of the gold nanoparticle superlattice domain has a modified molecule, and the modified molecule is suitable for reacting with the analyte to be detected and generating a Raman signal change. For analytes to be detected with a large Raman reflection cross section, there is no need to modify the surface of the gold nanoparticle superlattice domain, and detection can be performed directly. For analytes to be detected with a small Raman reflection cross section, it is necessary to modify the surface of the gold nanoparticle superlattice domain with a specific molecule, which can react with the analyte to be detected, and the Raman signals generated before and after the reaction are different, and the detection purpose is achieved based on the difference in Raman signals.

[0040] According to an embodiment of the present application, the material of the substrate includes silicon or polydimethylsiloxane (PDMS).

[0041] According to an embodiment of the present application, the shortest spacing between two adjacent gold nanoparticle superlattice domains is 200 μm to 250 μm, such as 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, and 250 μm. Thus, the wettability of the substrate and the gold nanoparticle superlattice domain surface can be better regulated, so as to facilitate the evaporation and shrinkage of the exhaled breath condensate droplets toward the hydrophilic gold nanoparticle superlattice domain.

[0042] According to an embodiment of the present application, the collecting piece is detachably disposed in the breathing valve body of the mask, thereby facilitating the removal and inspection of the collecting piece, facilitating the replacement and maintenance of the membrane, and being able to flexibly adjust or update the membrane according to usage requirements, thereby extending the service life of the mask and maintaining its performance stability.

[0043] It should be noted that the breathing valve of the mask of the present application can be a breathing valve commonly used in masks in the art, and does not need to be specially designed.

[0044] Face mask

[0045] In another aspect of the present application, the present application proposes an exhaled breath condensate collection mask. According to an embodiment of the present application, the exhaled breath condensate collection mask comprises a mask body, a breathing area is formed on the inner side of the mask body; the aforementioned mask breathing valve, the patterned gold nanoparticle superlattice film is connected to the breathing area.

[0046] The exhaled breath condensate collection mask of the present application does not need to use the traditional active condensation cooling module. A small amount of liquid sample generated by natural condensation at room temperature can be dried (for example, at room temperature or heated evaporation drying) and then combined with the surface enhanced Raman detection method to complete high-sensitivity analysis, which further reduces the dependence on a large number of samples, thereby simplifying the equipment design and reducing costs. In addition, the collection mask is based on the common breathing valve mask on the market, which is not only simple in structure, but also maintains low cost-effectiveness.

[0047] The patterned gold nanoparticle superlattice film in the mask of the present application can realize the efficient evaporation collection of analytes in condensed droplets, overcoming the problem that the traditional device cannot accurately control the distribution of analytes. In addition, the mask of the present application is highly portable and can be used in conjunction with a commercial breathing valve mask, and the collection of exhaled breath condensate can be achieved by directly wearing the mask. It overcomes the problem of poor portability of traditional condensation equipment due to the large size and weight of the equipment.

[0048] It should be noted that the features and advantages described above for the breathing valve for masks are also applicable to the exhaled gas condensate collection mask and will not be repeated here.

[0049] Applications and methods

[0050] In another aspect of the present application, the present application proposes the use of a breathing valve for a mask or a mask for collecting exhaled breath condensate in the preparation of a detection product. According to an embodiment of the present application, the detection product is used to detect exhaled breath condensate. The breathing valve in the mask of the present application contains a patterned gold nanoparticle superlattice film, and the exhaled breath condensate will evaporate and shrink directionally on its surface, thereby achieving a uniform and concentrated distribution of the analyte, overcoming the problem that traditional devices cannot accurately control the distribution of analytes. The purpose of accurately detecting exhaled breath condensate is achieved through Raman spectroscopy, with high detection sensitivity and suitable for wide application.

[0051] In another aspect of the present application, the present application proposes a method for detecting exhaled breath condensate. According to an embodiment of the present application, the method includes: allowing the subject to wear the exhaled breath condensate collection mask described above and breathe so as to form exhaled breath condensate droplets on the patterned gold nanoparticle superlattice film; and performing Raman spectroscopy detection on the patterned gold nanoparticle superlattice film after the exhaled breath condensate droplets are dried (such as at room temperature or heated for evaporation). Thus, the method of the present application can be used to detect analytes in exhaled breath condensate, which has the advantages of high sensitivity and high accuracy. The method can be used for the purpose of disease diagnosis or non-diagnosis, such as conducting scientific research on the composition of analytes in exhaled breath condensate, building analyte models, and screening drugs.

[0052] It should be noted that the features and advantages described above for the breathing valve and mask for masks are also applicable to this application and method and will not be repeated here.

[0053] The scheme of the present invention will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. Where specific techniques or conditions are not indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used are not indicated by the manufacturer and are all conventional products that can be obtained commercially.

[0054] Example 1

[0055] A preparation method for collecting exhaled breath condensate and a new detection method thereof, see Figure 1 , including the following steps:

[0056] 1. Silicon substrate surface modification trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane

[0057] The silicon substrate was modified by chemical vapor deposition (CVD) using trimethoxy (1H,1H,2H,2H-heptadecafluorodecyl) silane. Specifically, the silicon substrate was ultrasonically cleaned with water, ethanol, acetone, and isopropanol for 10 min, and then N 2Blow dry. Place the silicon substrate in a desiccator, drop 40 μL of trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane into the desiccator, evacuate for 30 min, and then heat at 170 degrees for 2 h.

[0058] The contact angle of the modified silicon substrate surface was measured to be 105°.

[0059] 2. Gold nanoparticles coated with oleylamine were prepared using a reduction method. Specifically, first, tetrachloroauric acid trihydrate (100 mg) was ultrasonically dissolved in a mixture of n-hexane and oleylamine (20 mL, volume ratio of 1:1), and the resulting mixture was placed in a three-necked flask and placed in a 4°C water bath. The reaction system was protected by argon. Then, borane tert-butylamine complex (0.25 mmol) was dissolved in a mixture of n-hexane and oleylamine (2 mL; volume ratio 1:1), and the reducing agent solution was quickly injected into the precursor solution. This caused the color of the solution to quickly change from orange to wine red, and the solution was stirred for 1 h until the reaction was complete. After the reaction was completed, ethanol (22 mL) was added to the reaction system to precipitate gold nanoparticles, and the resulting mixture was centrifuged (8000 rpm, 5 min) and washed. In addition, equal volumes of n-hexane and ethanol were added to the product obtained by centrifugation, and then washed three times. The final product was dissolved in n-hexane (10 mL) to obtain a gold nanoparticle solution (2.5 mg / mL).

[0060] 3. A patterned gold nanoparticle superlattice film was prepared on a silicon substrate by inkjet printing (silicon substrate size: 1 cm×1 cm). Each gold nanoparticle superlattice domain was distributed in a matrix pattern, each gold nanoparticle superlattice domain was 20 μm×20 μm in size, the spacing between two adjacent gold nanoparticle superlattice domains was 230 μm, and the contact angle of the gold nanoparticle superlattice domain was 60°.

[0061] 4. By horizontally fixing the patterned gold nanoparticle superlattice film on the inside of the breathing valve (the lower side of the breathing valve).

[0062] 5. Collect exhaled breath condensate by wearing a mask (collect for 8 minutes at 25°C).

[0063] 6. After the collection is completed, wait for the droplets to evaporate, use a microscopic confocal Raman spectrometer to collect Raman signals, and perform data analysis.

[0064] Figure 2 The optical microscope and scanning electron microscope characterizations of the patterned gold nanoparticle superlattice film prepared in step 3 are shown. The right side is a local magnified electron microscope photo of the selected area on the left side. Scale bars: 140 μm on the left and 30 nm on the right.

[0065] Depend on Figure 3The Raman imaging results on the right verify that the analyte can be uniformly and concentrated on the surface of the gold nanoparticle superlattice domain.

[0066] Depend on Figure 4 It can be seen that the concentration of hydrogen peroxide in the exhaled breath condensate of cold patients is higher than that of healthy people.

[0067] Example 2

[0068] 1. A patterned gold nanoparticle superlattice film was prepared according to steps 1-3 of Example 1, wherein 3-mercaptophenylboronic acid molecules were modified on the surface of the gold nanoparticle superlattice domains. The molecules were used to react with hydrogen peroxide to generate 3-mercaptobenzenethiol, thereby generating a change in the Raman peak and realizing the detection of hydrogen peroxide.

[0069] 2. Use a hydrogen peroxide solution of a certain concentration to make an exhaled breath condensate and apply it to the surface of the patterned gold nanoparticle superlattice film. Wait for the droplets to evaporate, use a microscopic confocal Raman spectrometer to collect Raman signals, and perform data analysis.

[0070] The results are as follows Figure 5 As shown, the upper and lower Raman spectra in the figure represent the Raman spectra before and after the hydrogen peroxide reaction. The concentration of hydrogen peroxide is determined based on the change of Raman spectral signals.

[0071] Depend on Figure 6 It can be seen that the method of the present application can accurately detect analytes of different concentrations, and the detection concentration can reach the micromolar level with high sensitivity.

[0072] Example 3

[0073] According to the method of Example 1, monitoring of different daily scenes is achieved respectively. Specifically, the subjects consume orange juice, milk, tea, beef, and chewing gum respectively.

[0074] The results are as follows Figure 7 As shown in the figure, from top to bottom are orange juice, milk, tea, beef, and chewing gum. It can be seen that the mask can be used to monitor different daily scenes, and the signal source is the food or drink itself or its digestion and metabolism products.

[0075] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A breathing valve for a mask, characterized in that: include: A breathing valve body, wherein the breathing valve body comprises an air inlet; A collecting member, which is disposed in the breathing valve body and is used to collect exhaled breath condensate; The collector includes a patterned gold nanoparticle superlattice film, and the patterned gold nanoparticle superlattice film is arranged toward the air inlet.

2. The breathing valve for a mask according to claim 1, characterized in that: The collection piece includes: substrate; A plurality of gold nanoparticle superlattice domains are arranged at intervals on a surface of the substrate facing the air inlet, each of the gold nanoparticle superlattice domains comprises a plurality of tightly packed gold nanoparticles, and the plurality of gold nanoparticle superlattice domains form the patterned gold nanoparticle superlattice film.

3. The breathing valve for a mask according to claim 2, characterized in that: The surface of the substrate facing the gold nanoparticle superlattice domain is modified with trimethoxy (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane; The surface of the gold nanoparticle superlattice domain has oleylamine molecules.

4. The breathing valve for a mask according to claim 3, characterized in that: The contact angle of the substrate is 100° to 110°, and the contact angle of the gold nanoparticle superlattice domain is 10° to 60°; The surface of the gold nanoparticle superlattice domain has modified molecules, and the modified molecules are suitable for reacting with the analyte to be detected and generating Raman signal changes.

5. The breathing valve for a mask according to claim 3 or 4, characterized in that: The material of the substrate includes silicon or polydimethylsiloxane.

6. The breathing valve for a mask according to claim 2, characterized in that: The shortest spacing distance between two adjacent gold nanoparticle superlattice domains is 200 μm to 250 μm.

7. The breathing valve for a mask according to claim 1, characterized in that: The collecting piece is detachably arranged in the breathing valve body of the mask.

8. A mask for collecting exhaled breath condensate, characterized in that: include: A mask body, wherein a breathing zone is formed on the inner side of the mask body; In the breathing valve for a mask according to any one of claims 1 to 7, the patterned gold nanoparticle superlattice film is connected to the breathing area.

9. Use of the breathing valve for a mask according to any one of claims 1 to 7 or the exhaled air condensate collection mask according to claim 8 in the preparation of a detection product, characterized in that: The detection product is used to detect exhaled breath condensate.

10. A method for detecting exhaled breath condensate for non-diagnostic purposes, characterized in that: include: Allowing a subject to wear the exhaled breath condensate collection mask of claim 8 and breathe so as to form exhaled breath condensate droplets on the patterned gold nanoparticle superlattice film; The patterned gold nanoparticle superlattice film after the exhaled breath condensate droplets are dried is subjected to Raman spectroscopy detection.

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