Colorimetric sensing chip for detecting lung cancer markers as well as preparation method and application of colorimetric sensing chip

Abstract

The invention relates to the technical field of medical detection, in particular to a colorimetric sensing chip for detecting lung cancer markers as well as a preparation method and application of the colorimetric sensing chip. Comprising a filter paper substrate, and an aromatic aldehyde gas sensing identification assembly, an alcohol ester gas sensing identification assembly, an aldehyde ketone gas sensing identification assembly, a first pH sensing assembly and a second pH sensing assembly which are integrated on the filter paper substrate, the aromatic aldehyde gas sensing recognition assembly is modified by gold superparticles GSPs; the alcohol ester gas sensing recognition assembly, the aldehyde ketone gas sensing recognition assembly, the first pH sensing assembly and the second pH sensing assembly are all modified by porous ZIF-8 nanoparticles; the colorimetric sensing chip disclosed by the invention is combined with various gas sensing components, is used for quantitatively detecting various lung cancer markers in exhaled gas by observing color change, can be realized without fluorescent labeling and expensive instruments, can finish rapid detection within 10 minutes through portable equipment such as a mobile phone and the like, has the sensitivity of 50ppb and improves the detection accuracy.

Description

Technical Field

[0001] The present invention relates to the field of medical detection technology, and in particular to a colorimetric sensor chip for detecting lung cancer markers, and a preparation method and application thereof. Background Art

[0002] Early detection and diagnosis are crucial for improving the cure rate of lung cancer and are key to increasing the survival rate of lung cancer patients. Traditional lung cancer detection methods mainly include invasive and non-invasive testing. Invasive testing can easily cause trauma and pain to patients and is not suitable for those in poor physical condition. Non-invasive testing, on the other hand, mostly relies on non-portable equipment or manual testing, which has problems such as long testing time and poor accessibility in non-fixed locations, resulting in many limitations in early lung cancer screening.

[0003] The emergence of portable testing methods, with their non-invasive, easy-to-use, flexible, and immediacy features, effectively addresses the shortcomings of traditional methods. Patients no longer have to endure the pain of blood draws or invasive sampling. The testing process is easy and convenient, unrestricted by time and space, and can be performed anytime, anywhere. From sample collection to results, it takes only a few minutes. This not only improves patient acceptance and compliance, but also provides clinicians with rapid and accurate diagnostic information, greatly improving diagnosis and treatment efficiency. It is a major innovation in testing technology.

[0004] In recent years, studies have found that exhaled breath contains a variety of volatile organic compounds (VOCs) associated with lung cancer, providing the possibility of non-invasive, portable testing. However, due to the low concentrations of some lung cancer markers in exhaled breath in patients with early-stage lung cancer, existing detection technologies have limited sensitivity and cannot accurately detect them, resulting in false-negative results and frequent misdiagnosis or missed diagnosis. To improve the accuracy of portable test results, it is often necessary to simultaneously detect multiple lung cancer markers. The potential of multi-marker combined detection further expands the application scope of portable testing, providing more comprehensive biomarker information for the accurate diagnosis and comprehensive management of lung cancer, and promoting lung cancer diagnosis and treatment towards the era of precision medicine. However, the detection methods and instruments for different markers may vary, the operating procedures are complex, and the testing costs are also increased accordingly. In addition, the interrelationships between the various markers and the comprehensive judgment of the diagnostic results are relatively complex, and there is a lack of unified standards and effective algorithms, which brings certain difficulties to diagnosis. This has led to an increasing demand for more convenient, rapid, and low-risk screening methods.

[0005] Colorimetric sensors have attracted widespread attention due to their advantages such as easy preparation, convenience of use, and observability to the naked eye. However, the content of lung cancer markers in human samples is usually low, and there are structural similarities between different lung cancer markers, which increases the difficulty of accurately identifying a single marker. Changes in the pH value of human samples will also change the chemical properties of the colorimetric reagent, thereby affecting the accuracy and repeatability of the color change. When using colorimetric sensors for detection, the colorimetric sensor must have extremely high sensitivity, specificity, and stability to ensure the stability of the test results. In addition, the simultaneous detection of multiple markers will increase the complexity of colorimetric sensor design and signal interpretation. The detection of different markers may require different reaction conditions and colorimetric systems. How to achieve simultaneous and accurate detection of multiple markers on a colorimetric sensor platform remains a challenge. Summary of the Invention

[0006] To address the above problems, the present invention provides a colorimetric sensor chip for detecting lung cancer markers, as well as its preparation method and application. Based on the local surface plasmon resonance effect, the chip observes color changes to achieve rapid and sensitive detection of multiple lung cancer markers in exhaled breath, significantly improving detection efficiency and accuracy.

[0007] A colorimetric sensor chip for detecting lung cancer markers, comprising a filter paper substrate and an aromatic aldehyde gas sensing and recognition component, an alcohol ester gas sensing and recognition component, an aldehyde ketone gas sensing and recognition component, a first pH sensing component, and a second pH sensing component integrated on the filter paper substrate;

[0008] The aromatic aldehyde gas sensing and identification component is modified with gold superparticles GSPs; the alcohol and ester gas sensing and identification component, the aldehyde and ketone gas sensing and identification component, the first pH sensing component and the second pH sensing component are all modified with porous ZIF-8 nanoparticles; wherein the interior of the gold superparticles is a three-dimensional ordered arrangement structure.

[0009] Furthermore, the indicator in the first pH sensing component is bromophenol blue; the indicator in the second pH sensing component is methyl red and bromocresol green.

[0010] The present invention also provides a method for preparing the above-mentioned colorimetric sensor chip for detecting lung cancer markers, including the synthesis of modifying materials, the preparation and post-processing of the colorimetric sensor chip. The preparation of the colorimetric sensor chip includes the formation of an aromatic aldehyde gas sensor recognition component on a filter paper substrate, and the integration of an alcohol ester gas sensor recognition component, an aldehyde ketone gas sensor recognition component, a first pH sensor component, and a second pH sensor component on the same filter paper substrate.

[0011] Among them, the aromatic aldehyde gas sensing and identification component is formed by directly adding a gold superparticle dispersion onto a filter paper substrate; the alcohol ester gas sensing and identification component, the aldehyde ketone gas sensing and identification component, the first pH sensing component and the second pH sensing component are formed by adding porous ZIF-8 nanoparticles to their respective raw material solutions, and after ultrasonic treatment, they are respectively added onto the same filter paper substrate as the aromatic aldehyde gas sensing and identification component to integrate and obtain a colorimetric sensor chip.

[0012] Furthermore, the amount of porous ZIF-8 nanoparticles added was 5 mg, the ultrasonic treatment time was 3 min, and the amount added dropwise to the filter paper substrate was 2 uL;

[0013] Furthermore, the raw material solution of the alcohol and ester gas sensor identification component is a 1 mg / mL aqueous solution of merocyanine 540; the raw material solution of the aldehyde and ketone gas sensor identification component is a 10 mg / mL rosaniline methoxyethanol solution; the raw material solution of the first pH sensor component is a 1 mg / mL bromophenol blue ethanol solution; and the raw material solution of the second pH sensor component is a 1 mg / mL and 2 mg / mL methylated-bromocresol green ethanol solution, respectively.

[0014] Furthermore, the post-processing process includes placing the colorimetric sensor chip in an inert gas environment at room temperature for at least 2 hours.

[0015] Furthermore, the synthesis of the modified material comprises the following steps:

[0016] (1) Preparation of gold nanoparticles: Using a mixture of borane-tert-butylamine complex to reduce a mixture of chloroauric acid tetrahydrate to obtain monodispersed gold nanoparticles;

[0017] (2) Synthesis of gold superparticles: The monodispersed gold nanoparticles prepared in step (1) are centrifuged and then redispersed in a chloroform solution, and three-dimensionally ordered gold superparticles are assembled by a solution self-assembly method;

[0018] (3) Preparation of porous ZIF-8 nanoparticles: DTAB aqueous solution was added to 2-methylimidazole aqueous solution, and zinc nitrate aqueous solution was quickly added after vigorous stirring. After standing for 5 h, the mixture was centrifuged and washed with ethanol and ultrapure water, and vacuum dried to obtain porous ZIF-8 nanoparticles.

[0019] Furthermore, in step (1), the mixed solution is n-octane and oleylamine in a volume ratio of 1:1, the reaction temperature is 5-20°C, the stirring speed is 700r / min, and the stirring time is 1h;

[0020] Furthermore, the solutions used for the assembly in step (2) are aqueous dodecyltrimethylammonium bromide solution and aqueous polyvinylpyrrolidone solution; the volumes of the aqueous dodecyltrimethylammonium bromide solution and aqueous polyvinylpyrrolidone solution are equal to the volume of the gold nanoparticle dispersion.

[0021] Furthermore, the concentration of the dodecyltrimethylammonium bromide aqueous solution is 10 to 40 mg / mL, and the concentration of the polyvinylpyrrolidone aqueous solution is 10 to 40 mg / mL;

[0022] Furthermore, in step (2), chloroform is removed by bubbling argon gas, the bubbling temperature is 40-60° C., and the bubbling time is 30 min.

[0023] Furthermore, in step (3), the concentration of the 2-methylimidazole aqueous solution is 1.5-5 mol / L, the concentration of the DTAB aqueous solution is 10-40 mg / mL, and the concentration of the zinc nitrate aqueous solution is 20-40 mM, and the volume ratio of the three is 10:0.2:10;

[0024] Furthermore, in step (3), the vacuum drying time is 5 hours at a temperature of 100 to 120°C.

[0025] The present invention also provides the use of the colorimetric sensor chip or the colorimetric sensor chip prepared by the above preparation method in an exhaled breath colorimetric detection sensor.

[0026] Furthermore, the exhaled breath colorimetric detection sensor includes a shell, a gas flow channel located inside the shell, and a one-way gas valve located outside the shell. The gas flow channel is a fishbone structure with several baffles inside; one end of the one-way gas valve is connected to the gas flow channel, and the other end is connected to an L-shaped gas pipeline; a portable color comparison camera is provided on the shell, and the colorimetric sensor chip is located in the center of the gas flow channel and is symmetrically arranged with the portable color comparison camera.

[0027] The present invention provides the use of the colorimetric sensor chip or the colorimetric sensor chip prepared by the above preparation method in an exhaled breath colorimetric detection sensor.

[0028] The present invention also provides the use of the colorimetric sensor chip or the colorimetric sensor chip prepared by the above preparation method in exhaled breath detection.

[0029] Furthermore, it is used to quantitatively detect multiple lung cancer markers in exhaled breath.

[0030] Furthermore, the process of quantitatively detecting multiple lung cancer markers in exhaled breath is as follows:

[0031] (1) Place the colorimetric sensor chip in the gas flow path of the exhalation device, seal the device, and blow air using a blowing device;

[0032] (2) Using the flash of a portable color comparison camera as a light source, take photos before and after the gas reaction;

[0033] (3) Obtain the colorimetric card and RGB values, and calculate the Euclidean distance ΔE using the RGB values;

[0034] (4) The concentration values ​​of various volatile organic compounds in exhaled breath were obtained based on the calibration curve.

[0035] The advantages of the present invention are:

[0036] 1. The present invention utilizes the three-dimensional ordered structure of gold superparticles to change the aggregation pattern of nanoparticles, increasing the number of effective fusion sites. By modifying the oleylamine ligand that specifically recognizes aromatic aldehydes, it can effectively capture the lung cancer marker 3-ethylbenzaldehyde. On the one hand, the ligand that specifically binds to 3-ethylbenzaldehyde is detached, and on the other hand, the detached nanoparticles aggregate and fuse with each other. This gives the colorimetric sensor excellent specificity and sensitivity for early lung cancer screening, significantly improving the accuracy of lung cancer marker detection.

[0037] 2. The sensor chip of the present invention combines multiple gas sensing components, each of which has high sensitivity to specific compounds, ensuring more sensitive and specific detection of multiple different gas molecules. While effectively improving selectivity and sensitivity, it can also utilize the response patterns of different components to more accurately identify and analyze some complex gas environments, improving the sensor's detection specificity and accuracy for multiple different gas molecules, and realizing the simultaneous detection of low-concentration multiple markers in exhaled breath;

[0038] 3. The exhaled breath colorimetric detection sensor provided by the present invention is compact and easy to operate. Based on the local surface plasmon resonance effect, it can be used to quantitatively detect various lung cancer markers in exhaled breath by observing color changes. This can be achieved without fluorescent labeling and expensive instruments. Rapid detection can be completed within 10 minutes using portable devices such as mobile phones, with a sensitivity of up to 50 ppb. This solves the problem of low sensitivity and poor repeatability in existing detection methods, which are mostly non-portable devices or manual detection methods, leading to missed detections and false positives. It provides new ideas for the development of simple and highly sensitive optical bioassay platforms. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Schematic diagram of a colorimetric sensor chip for detecting lung cancer markers according to the present invention;

[0040] Figure 2Schematic diagram of the structure of the exhaled breath colorimetric detection sensor for detecting lung cancer markers according to the present invention;

[0041] Figure 3 This is the detection result diagram of the colorimetric sensor chip of the present invention ( Figure 3 a is the color card, Figure 3 b is a linear relationship curve between concentration and Euclidean distance ΔE);

[0042] Figure 4 This is a sensitivity test result diagram of the colorimetric sensor chip of the present invention;

[0043] Reference numerals:

[0044] 1. Housing; 2. Gas flow channel; 3. Baffle; 4. Colorimetric sensor chip; 5. One-way gas valve; 6. L-shaped gas pipeline; 7. Portable color comparison camera. DETAILED DESCRIPTION

[0045] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0046] It should be noted that the various installation methods and technical terms mentioned in the present invention are technical terms that have long been clearly known in the relevant technical field and therefore will not be further explained. In addition, the same reference numerals are used for the same components, but this does not affect nor constitute an accurate understanding of the technical solution by those skilled in the art.

[0047] Example 1

[0048] This embodiment provides a colorimetric sensor chip for detecting lung cancer markers, including a filter paper substrate and an aromatic aldehyde gas sensor and recognition component, an alcohol ester gas sensor and recognition component, an aldehyde and ketone gas sensor and recognition component, a first pH sensor component, and a second pH sensor component integrated on the filter paper substrate. The preparation process is as follows:

[0049] Step 1: Synthesis of Modified Materials

[0050] (1) Preparation of gold nanoparticles with high monodispersity:

[0051] 100 mg of tetrachloroauric acid trihydrate was ultrasonically dissolved in 20 ml of a mixed solution of n-octane and oleylamine (volume ratio = 1:1). The mixed solution was placed in a constant temperature water bath at 20°C, protected by argon and magnetically stirred at a speed of 700 r / min. The mixture was kept for 15 min. 2 ml of a mixed solution of n-octane and oleylamine (volume ratio = 1:1) containing 0.25 mmol of borane-tert-butylamine complex was quickly injected. The reaction solution quickly turned deep red. The temperature was maintained and the reaction was continued for 1 h. After the reaction was completed, 20 ml of anhydrous ethanol was added and the mixture was centrifuged at a speed of 6500 rpm for 5 min. The product obtained by centrifugation was added with 10 mL of n-hexane and 10 mL of anhydrous ethanol and washed three times by centrifugation to obtain highly monodisperse gold nanosphere particles.

[0052] (2) Synthesis of three-dimensional ordered gold superparticles:

[0053] The monodispersed gold nanoparticles in step (1) are redispersed in 10 mL of chloroform solution to obtain a gold nanoparticle dispersion having a high monodispersity and a size of about 5.8 nm; 1 mL of a 10 mg / mL aqueous solution of dodecyltrimethylammonium bromide is added to 1 mL of the gold nanoparticle dispersion and vortexed for 1 minute to obtain an oil-in-water microemulsion; argon is introduced into the emulsion for bubbling at a temperature of 40° C. for 30 minutes until the chloroform is completely removed, and after cooling to room temperature, 1 mL of a 10 mg / mL aqueous solution of polyvinylpyrrolidone is added and stirred for 10 minutes. After standing for 3 hours, the dispersion is centrifuged at a speed of 2500 rpm for 3 minutes and redispersed in 1 mL of ultrapure water to obtain three-dimensional ordered gold superparticles protected by polyvinylpyrrolidone;

[0054] (3) Preparation of porous ZIF-8 nanoparticles:

[0055] To 10 mL of 1.5 mol / L 2-methylimidazole aqueous solution, 0.2 mL of 10 mg / mL DTAB aqueous solution was added. After vigorous stirring, 10 mL of 20 mM zinc nitrate aqueous solution was quickly added. After standing for 5 h, the mixture was centrifuged and washed three times with ethanol and ultrapure water respectively. After drying in vacuum at 100 °C for 5 h, porous ZIF-8 nanoparticles were obtained.

[0056] Step 2: Preparation of colorimetric sensor chip:

[0057] The gold superparticle dispersion described in S1 is directly added dropwise to the filter paper substrate to form an aromatic aldehyde recognition component; the above-mentioned ZIF-8 particles are added to a merocyanine 540 aqueous solution (1 mg / ml), and after ultrasonic treatment, the particles are added dropwise to the same filter paper substrate; the above-mentioned ZIF-8 particles are added to a rosaniline methoxyethanol solution (10 mg / ml), and after ultrasonic treatment, the particles are added dropwise to the same filter paper substrate; the above-mentioned ZIF-8 particles are added to a bromophenol blue ethanol solution (1 mg / ml), and after ultrasonic treatment, the particles are added dropwise to the same filter paper substrate; the above-mentioned ZIF-8 particles are added to a methyl red-bromocresol green ethanol solution (1 mg / ml, 2 mg / ml), and after ultrasonic treatment, the particles are added dropwise to the same filter paper substrate;

[0058] Step 3: Post-processing of the colorimetric sensor chip:

[0059] The filter paper substrate of the colorimetric sensor chip with the five sensor components added thereto obtained in step 2 is placed in an inert gas environment at room temperature for more than 2 hours to obtain a colorimetric sensor chip with stable response.

[0060] Example 2

[0061] This embodiment is the same as embodiment 1, except that the preparation process parameters of the colorimetric sensor chip are different:

[0062] In the preparation of gold nanoparticles with high monodispersity in step (1) of this embodiment, the reaction temperature is 5°C;

[0063] In the synthesis of the three-dimensional ordered gold superparticles in step (2) of this embodiment, the concentration of the dodecyltrimethylammonium bromide aqueous solution is 40 mg / mL, the concentration of the polyvinylpyrrolidone aqueous solution is 40 mg / mL, and the bubbling temperature is 60° C.

[0064] In the preparation of porous ZIF-8 nanoparticles in step (3) of this embodiment, the concentration of the 2-methylimidazole aqueous solution is 5 mol / L, the concentration of the DTAB aqueous solution is 40 mg / mL, the concentration of the zinc nitrate aqueous solution is 40 mM, and the vacuum drying time and temperature are 120°C.

[0065] Example 3

[0066] Based on the colorimetric sensor chip for detecting lung cancer markers described in Example 1, this embodiment provides an exhaled breath colorimetric detection sensor, such as Figure 2As shown, the device comprises a housing 1, a gas flow channel 2 located within the housing 1, and a one-way gas valve 5 located outside the housing. The gas flow channel 2 has a fishbone structure and is equipped with several baffles 3. One end of the one-way gas valve 5 is connected to the gas flow channel 2, and the other end is connected to an L-shaped gas pipeline 6. A portable color comparison camera 7 is mounted on the housing 1, and the colorimetric sensor chip 4 is located in the center of the gas flow channel 2 and is symmetrically arranged with the portable color comparison camera 7. The exhaled breath colorimetric detection sensor also includes a sealing cover for sealing the detection device.

[0067] Test Example 1: Sensitivity Detection

[0068] A variety of volatile exhaled breath organic compounds, including 3-ethylbenzaldehyde, benzaldehyde, nonanal, valeraldehyde, salicylaldehyde, and formaldehyde, with known concentrations of 50 ppb, 100 ppb, 300 ppb, 500 ppb, 1000 ppb, 5000 ppb, and 10000 ppb, were obtained. A colorimetric sensor chip was prepared using the method of Example 1 for sensitivity detection. The detection process was as follows:

[0069] (1) placing the colorimetric sensor chip in a closed chamber and introducing the above-mentioned gas to react;

[0070] (2) Using a flashlight as a light source, a portable color comparison camera was used to take photos of the ventilatory response before and after (in this embodiment, a Huawei P30 mobile phone equipped with a stick-on universal magnifying lens was used to take the before and after photos);

[0071] (3) Obtaining a colorimetric card and RGB values, and calculating the Euclidean distance ΔE using the RGB values;

[0072] (4) Obtain the linear range, detection limit and calibration curve based on various concentration values, and calculate the detection limit.

[0073] Test results such as Figure 3 and Figure 4 As shown, Figure 3 a is the colorimetric card for the test results, Figure 3 b is a linear relationship curve between the concentrations of six volatile exhaled breath organic compounds and the Euclidean distance ΔE, indicating that the colorimetric sensor chip responds differently to substances of different concentrations. The concentration-response relationship can be established through this curve for quantitative detection of the concentration of the target substance. Figure 4 The sensitivity test results of the colorimetric sensor chip to six different volatile exhaled breath organic compounds are shown in Figure 2. Figure 3 and Figure 4The results show that the colorimetric sensor chip prepared by the method of Example 1 has a good response and high sensitivity to volatile organic compounds in exhaled breath, among which the minimum detection limit of 3-ethylbenzaldehyde, salicylaldehyde, and benzaldehyde is as low as 0.05 ppm (corresponding to a concentration of 50 ppb), and the minimum detection limit of nonanal, valeraldehyde, and formaldehyde is 0.3 ppm (corresponding to a concentration of 300 ppb).

[0074] Test Example 2: Practical Application Test

[0075] The present invention places the colorimetric sensor chip for detecting lung cancer markers described in Example 1 into the exhaled breath colorimetric detection sensor described in Example 3 to conduct a practical application test. The usage process is as follows:

[0076] During use, the subject needs to rinse their mouth three times with ultrapure water, place the colorimetric sensor chip in the center of the gas flow channel of the exhaled breath colorimetric detection sensor, seal the exhaled breath colorimetric detection sensor, and use an L-shaped gas pipeline to exhaust gas, with a one-way gas valve controlling the gas flow into the gas flow channel. Using the mobile phone flash as the light source, a Huawei P30 mobile phone equipped with a snap-on universal magnifying lens takes two before and after photos. The Euclidean distance ΔE is calculated from the RGB values, and the concentration values ​​of various volatile organic compounds in the exhaled breath of lung cancer patients are obtained based on the calibration curve in Test Example 1.

[0077] The results of practical application tests show that the colorimetric sensor chip of the present invention can achieve rapid detection within 10 minutes through portable devices such as mobile phones, and the detection sensitivity of 3-ethylbenzaldehyde in lung cancer markers is as low as 50 ppb.

[0078] The present invention is based on a colorimetric method for the quantitative detection of various lung cancer markers in exhaled breath. It is small in size, easy to operate, does not require fluorescent labeling, and does not require expensive laboratory instruments and professional technicians. It solves the problem that the existing detection methods are mostly non-portable equipment or manual detection methods, with low sensitivity and poor repeatability, which lead to missed detections and false positives. It provides new ideas for the development of a simple and highly sensitive optical biological detection platform.

[0079] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention may be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the present invention is defined by the appended claims rather than the foregoing description. It is intended that all variations that fall within the meaning and range of equivalents of the claims be embraced within the present invention. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

[0080] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any minor modifications, equivalent replacements, and improvements made to the above embodiments based on the technical essence of the present invention shall be included in the scope of protection of the technical solution of the present invention.

Claims

1. A colorimetric sensor chip for detecting lung cancer markers, characterized in that: It includes a filter paper substrate and an aromatic aldehyde gas sensing and identification component, an alcohol ester gas sensing and identification component, an aldehyde ketone gas sensing and identification component, a first pH sensing component and a second pH sensing component integrated on the filter paper substrate; The aromatic aldehyde gas sensing and identification component is modified with gold superparticles GSPs; the alcohol and ester gas sensing and identification component, the aldehyde and ketone gas sensing and identification component, the first pH sensing component and the second pH sensing component are all modified with porous ZIF-8 nanoparticles; wherein the interior of the gold superparticles is a three-dimensional ordered arrangement structure.

2. The colorimetric sensor chip for detecting lung cancer markers according to claim 1, characterized in that: The indicator in the first pH sensing component is bromophenol blue; the indicator in the second pH sensing component is methyl red and bromocresol green.

3. A method for preparing a colorimetric sensor chip for detecting lung cancer markers based on claim 1, comprising synthesis of a modification material → preparation of a colorimetric sensor chip → post-processing, characterized in that: The post-processing process includes placing the colorimetric sensor chip in an inert gas environment at room temperature for at least 2 hours; The preparation of the colorimetric sensor chip includes forming an aromatic aldehyde gas sensing and identification component on a filter paper substrate, and integrating an alcohol and ester gas sensing and identification component, an aldehyde and ketone gas sensing and identification component, a first pH sensing component, and a second pH sensing component on the same filter paper substrate; Among them, the aromatic aldehyde gas sensing and identification component is formed by directly adding a gold superparticle dispersion onto a filter paper substrate; the alcohol ester gas sensing and identification component, the aldehyde ketone gas sensing and identification component, the first pH sensing component and the second pH sensing component are formed by adding porous ZIF-8 nanoparticles to their respective raw material solutions, and after ultrasonic treatment, they are respectively added onto the same filter paper substrate as the aromatic aldehyde gas sensing and identification component to integrate and obtain a colorimetric sensor chip.

4. The method for preparing a colorimetric sensor chip for detecting lung cancer markers according to claim 3, wherein: The amount of porous ZIF-8 nanoparticles added was 5 mg, the ultrasonic treatment time was 3 min, and the amount added dropwise to the filter paper substrate was 2 uL; The raw material solution of the alcohol and ester gas sensor identification component is a 1 mg / mL aqueous solution of merocyanine 540; the raw material solution of the aldehyde and ketone gas sensor identification component is a 10 mg / mL rosaniline methoxyethanol solution; the raw material solution of the first pH sensor component is a 1 mg / mL bromophenol blue ethanol solution; the raw material solution of the second pH sensor component is a 1 mg / mL and 2 mg / mL methylated bromocresol green ethanol solution.

5. The method for preparing a colorimetric sensor chip for detecting lung cancer markers according to claim 3, wherein: The synthesis of the modified material comprises the following steps: (1) Preparation of gold nanoparticles: Using a mixture of borane-tert-butylamine complex to reduce a mixture of chloroauric acid tetrahydrate to obtain monodispersed gold nanoparticles; (2) Synthesis of gold superparticles: The monodispersed gold nanoparticles prepared in step (1) are centrifuged and then redispersed in a chloroform solution, and three-dimensionally ordered gold superparticles are assembled by a solution self-assembly method; (3) Preparation of porous ZIF-8 nanoparticles: DTAB aqueous solution was added to 2-methylimidazole aqueous solution, and zinc nitrate aqueous solution was quickly added after vigorous stirring. After standing for 5 h, the mixture was centrifuged and washed with ethanol and ultrapure water, and vacuum dried to obtain porous ZIF-8 nanoparticles.

6. The method for preparing a colorimetric sensor chip for detecting lung cancer markers according to claim 5, wherein: In step (1), the mixed liquid is n-octane and oleylamine in a volume ratio of 1:1, the reaction temperature is 5-20°C, the stirring speed is 700r / min, and the stirring time is 1h; The solutions used for the assembly in step (2) are a dodecyltrimethylammonium bromide aqueous solution and a polyvinylpyrrolidone aqueous solution; the volumes of the dodecyltrimethylammonium bromide aqueous solution and the polyvinylpyrrolidone aqueous solution are equal to the volume of the gold nanoparticle dispersion; the concentration of the dodecyltrimethylammonium bromide aqueous solution is 10 to 40 mg / mL, and the concentration of the polyvinylpyrrolidone aqueous solution is 10 to 40 mg / mL; In the step (2), chloroform is removed by bubbling argon gas at a temperature of 40 to 60° C. for 30 minutes.

7. The method for preparing a colorimetric sensor chip for detecting lung cancer markers according to claim 6, wherein: In step (3), the concentration of the 2-methylimidazole aqueous solution is 1.5-5 mol / L, the concentration of the DTAB aqueous solution is 10-40 mg / mL, and the concentration of the zinc nitrate aqueous solution is 20-40 mM, and the volume ratio of the three is 10:0.2:10; Wherein, the vacuum drying time temperature in said step (3) is 100-120° C. and the time is 5 h.

8. Use of the colorimetric sensor chip for detecting lung cancer markers according to claim 1 or the colorimetric sensor chip prepared by the preparation method according to any one of claims 1 to 7 in an exhaled breath colorimetric detection sensor, characterized in that: The exhaled breath colorimetric detection sensor comprises a housing (1), a gas flow channel (2) located inside the housing (1), and a one-way gas valve (5) located outside the housing (1); the gas flow channel (2) is a fishbone structure and is provided with a plurality of baffles (3) inside; one end of the one-way gas valve (5) is connected to the gas flow channel (2), and the other end is connected to an L-shaped gas pipeline (6); a portable color comparison camera (7) is provided on the housing (1), and the colorimetric sensor chip (4) is located at the center of the gas flow channel (2) and is symmetrically arranged with the portable color comparison camera (7).

9. Use of the colorimetric sensor chip according to claim 1 or the colorimetric sensor chip prepared by the preparation method according to any one of claims 1 to 7 in exhaled breath detection, characterized in that: Used for quantitative detection of multiple lung cancer markers in exhaled breath.

10. The use according to claim 9, characterized in that The process for quantitative detection of multiple lung cancer markers in exhaled breath is as follows: (1) Place the colorimetric sensor chip in the gas flow path of the exhalation device, seal the device, and blow air using a blowing device; (2) Using the flash of a portable color comparison camera as a light source, take photos before and after the gas reaction; (3) Obtain the colorimetric card and RGB values, and calculate the Euclidean distance ΔE using the RGB values; (4) The concentration values ​​of various volatile organic compounds in exhaled breath were obtained based on the calibration curve.

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