Biomarker for detecting colorectal cancer as well as detection sensor and application thereof

Abstract

The invention relates to a biomarker for detecting colorectal cancer as well as a detection sensor and application thereof. The biomarker comprises isopropanol and / or p-cresol. The characteristic gas marker capable of being used for colorectal cancer diagnosis is successfully screened out, a polycrystalline zinc oxide material with a specific crystal face structure is prepared, the excellent catalytic oxidation performance is shown, and a detection sensor developed according to the method has the advantages of being rapid in response, high in sensitivity, good in specificity and the like. The invention provides an innovative solution for clinical colorectal cancer screening, and has a remarkable clinical application value in the field of early diagnosis of tumors.

Description

Technical Field

[0001] The present invention belongs to the technical field of biological detection, and relates to biomarkers for detecting colorectal cancer, their detection sensors and applications. Background Art

[0002] Colorectal Cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related deaths. Early diagnosis is the key to improving the prognosis of patients: the 5-year survival rate of stage I colorectal cancer can reach over 90%, while that of stage IV is less than 15%.

[0003] Currently, the widely used diagnostic method is to directly detect by colonoscopy, and during this process, benign adenomas with a small range of minor trauma are removed. The colonoscope is usually equipped with a camera and a retractable blade for minimally invasive surgery. However, this method requires the patient to perform intestinal preparation the day before, and during this process, a large amount of defecation is needed in a short time to empty the feces inside the intestine for easy observation by the colonoscope. This method will cause many discomforts during the patient's preparation stage and recovery stage. In addition, the colonoscopy method is not suitable for the elderly population, especially those over 70 years old. Other detection methods also include fecal occult blood test, which is non-invasive, low-cost, suitable for large-scale screening, but has low sensitivity (about 70% for advanced cancer and only 30 - 50% for early cancer), is easily interfered by diet or drugs, and has a high false positive rate; fecal DNA detection, which detects DNA methylation (such as NDRG4, BMP3) and KRAS mutations, etc., has high detection sensitivity, but is costly, complex to operate, and cannot locate the lesion position.

[0004] It can be seen that there are still problems in current clinical practice, such as low screening rate, poor compliance, insufficient sensitivity of early detection technology, complex operation or high cost. Developing new markers and detection means has become a key concern in the field of colorectal cancer diagnosis. For example, CN115372490A discloses a diagnostic product for assessing the risk of adenoma and colorectal cancer in a subject. The diagnostic indicators of the diagnostic product include one or more of taurocholic acid, fumaric acid, myristic acid, histidine, tyrosine, 3,4-dihydroxycinnamic acid in the biological sample of the subject, and optionally include the following combinations or one of them: quantitatively detecting the biomarker combination in the biological sample by chromatographic mass spectrometry metabolomics analysis method, and the chromatographic mass spectrometry metabolomics analysis method includes liquid chromatography mass spectrometry metabolomics analysis method and gas chromatography mass spectrometry metabolomics analysis method. However, the above methods require expensive instrument equipment and trained personnel.

[0005] In summary, developing new markers and efficient and low-cost detection means is of great significance for the field of colorectal cancer diagnosis. Summary of the Invention

[0006] In view of the deficiencies of the prior art and the actual needs, the present invention provides biomarkers for detecting colorectal cancer, as well as detection sensors and applications thereof, aiming to discover biomarkers for detecting colorectal cancer and further develop detection sensors, so as to achieve efficient, low-cost and rapid early screening.

[0007] To achieve this purpose, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides biomarkers for detecting colorectal cancer, and the biomarkers include isopropanol and / or p-cresol.

[0009] In the present invention, samples of the adenoma group, the healthy group and the colorectal cancer group are deeply analyzed, and it is found that there are significant differences in the contents of isopropanol and p-cresol in the headspace gas of fecal samples. The contents of isopropanol and p-cresol in the colorectal cancer group are significantly increased, proving that the two have the potential to be used as biomarkers for screening colorectal cancer.

[0010] In a second aspect, the present invention provides the use of the biomarkers for detecting colorectal cancer described in the first aspect and / or their detection reagents in the preparation of colorectal cancer auxiliary diagnosis or diagnostic products.

[0011] Based on the biomarkers discovered by the present invention, colorectal cancer auxiliary diagnosis or diagnostic products can be further prepared.

[0012] In a third aspect, the present invention provides a gas sensor, which includes zinc oxide; the zinc oxide has crystal lattices of (-1, 0, 0), (0, 0, -2) and (-1, 0, -1); the gas detected by the gas sensor includes the biomarkers for detecting colorectal cancer described in the first aspect.

[0013] In the present invention, a gas sensor is further designed and prepared by using zinc oxide with specific crystal lattices. The specific catalytic reaction of isopropanol at 40 °C is carried out by using three crystal planes of (-1, 0, 0), (0, 0, -2) and (-1, 0, -1) of zinc oxide, so that isopropanol is catalytically oxidized into carbon dioxide and water and electrons are generated with the assistance of O2 adsorbed on the surface. The electron transfer generated in this process is detected by a zinc oxide system based on the surface of the interdigitated impedance electrode to detect trace isopropanol volatilized from the headspace, and rapid and accurate detection can be achieved. The specific reaction process is as follows: - With the assistance of O2 adsorbed on the surface, isopropanol is catalytically oxidized into carbon dioxide and water and electrons are generated. The electron transfer generated in this process is detected by a zinc oxide system based on the surface of the interdigitated impedance electrode to detect trace isopropanol volatilized from the headspace, and rapid and accurate detection can be achieved. The specific reaction process is as follows:

[0014] O 2(gas) →O 2(ads) Equation 1;

[0015]

[0016] Preferably, the gas sensor further includes at least one of a breadboard, patch cords, jumpers, an amplifier circuit, or an analog-to-digital conversion unit, etc.

[0017] Preferably, the breadboard is used for connecting with the sensor, the patch cords are used for connecting to the downstream amplifier circuit, and the analog-to-digital conversion unit is used for outputting signals at the end.

[0018] Preferably, the preparation method includes: preparing zinc oxide, and using the zinc oxide to prepare a gas sensor; the method for preparing zinc oxide includes: performing electrochemical deposition using zinc ions as raw materials.

[0019] Preferably, the time for the electrochemical deposition is 10 - 80 min, for example, it can be 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 76, 77, 78, or 79 min, etc., preferably 30 - 50 min, more preferably 35 - 45 min, and even more preferably 39 - 41 min.

[0020] In the present invention, by changing the parameters related to the electrochemical deposition process, the degree of crystal exposure is adjusted, and then through the structure-activity relationship, the catalytic crystal state required for the reaction catalysis is optimized to achieve the best catalytic effect for isopropanol.

[0021] Preferably, the electrochemical deposition is carried out under constant voltage, and the voltage is -1.6 V to -1.4 V.

[0022] Preferably, the reference electrode for the electrochemical deposition is silver / silver chloride.

[0023] Preferably, the electrolyte for the electrochemical deposition includes a potassium chloride solution.

[0024] Preferably, the temperature of the electrolyte is 65 - 95 °C, for example, it can be 66, 67, 68, 69, 70, 71, 72, 75, 80, 85, 90, 91, 92, 93, or 94 °C, etc.

[0025] Preferably, after the electrochemical deposition, there is also a step of calcination.

[0026] Preferably, the conditions for the calcination include: calcining at 400 - 500 °C for 30 - 60 min, and the heating rate is 2 - 2.5 °C / min.

[0027] Fourthly, the present invention provides a method for detecting isopropanol, and the detection method includes: detecting using the gas sensor described in the third aspect.

[0028] In the present invention, the designed gas sensor can rapidly detect isopropanol with high accuracy and sensitivity. The specific method can be applied to disease diagnosis and the detection of isopropanol for other non-disease diagnosis purposes.

[0029] In a fifth aspect, the present invention provides a device for diagnosing colorectal cancer, which comprises:

[0030] a detection unit for detecting the content of the biomarker for detecting colorectal cancer described in the first aspect in the headspace gas of the sample to be tested;

[0031] an analysis unit for making a determination by using the content of the biomarker detected by the detection unit.

[0032] Preferably, the sample to be tested includes a fecal sample.

[0033] Preferably, the detection method includes detecting by using the gas sensor described in the third aspect and / or performing gas chromatography-mass spectrometry detection.

[0034] In the present invention, the combined detection and mutual verification of a gas chromatography-mass spectrometer and a gas sensor can be utilized.

[0035] Preferably, the criteria for determining positive colorectal cancer include: isopropanol ≥ 1.0 ppb and / or p-cresol ≥ 0.055 ppb (criteria for a 200 mg fecal sample); or, the isopropanol sensor signal value of cancer patients / healthy people ≥ 2:1; the p-cresol concentration value of cancer patients / healthy people ≥ 77:1.

[0036] Preferably, when the p-cresol concentration value of cancer patients / healthy people ≥ 50:1 and < 77:1, it is an adenoma.

[0037] Compared with the prior art, the present invention has at least the following beneficial effects:

[0038] The present invention has successfully screened out characteristic gas markers for colorectal cancer diagnosis. On this basis, the screened gas markers are innovatively combined with electrochemical sensing technology. By precisely controlling the parameters of the electrochemical deposition process, the directional growth of polycrystalline crystals in the Z-axis direction and the exposure of active crystal planes are successfully achieved. Experimental results show that the prepared polycrystalline zinc oxide material with a specific crystal plane structure exposed exhibits excellent catalytic oxidation performance for the characteristic headspace gas markers of colorectal cancer. The developed detection sensor has the advantages of rapid response, high sensitivity, and good specificity. It not only provides a new biomarker system for non-invasive diagnosis of colorectal cancer, but also the constructed sensor has the characteristics of simple operation and low cost, providing an innovative solution for clinical colorectal cancer screening and having significant clinical application value in the field of early tumor diagnosis. Description of the Drawings

[0039] Figure 1 It is a schematic diagram of the operation for detecting the headspace gas of fecal samples by a gas chromatography - mass spectrometer.

[0040] Figure 2 It is a schematic diagram of the operation for detecting isopropanol or p - cresol standards by a gas chromatography - mass spectrometer.

[0041] Figure 3 It is a gas chromatography - mass spectrometry detection result diagram of isopropanol and p - cresol standards. Among them, Figure A is the response diagram of isopropanol by a gas chromatography - mass spectrometer in the concentration ranges of 0.112 ppb, 1.12 ppb, 11.2 ppb, 28.0 ppb, and 58.0 ppb, and Figure B is its fitting equation and linear range; Figure C is the response spectrum of p - cresol in the ranges of 0.0104 ppb, 0.0520 ppb, 0.104 ppb, 0.520 ppb, and 1.04 ppb, and Figure D is the corresponding peak area fitting equation and linear range.

[0042] Figure 4 It is a morphology result diagram of zinc oxide prepared by scanning electron tunneling microscopy and transmission electron microscopy. Among them, Figures A, E, and I are the morphologies of modified zinc oxide prepared by electrodeposition for 10 min, Figures B, F, and J are the morphologies of modified zinc oxide prepared by electrodeposition for 20 min, Figures C, G, and K are the morphologies of modified zinc oxide prepared by electrodeposition for 40 min, and Figures D, H, and L are the morphologies of modified zinc oxide prepared by electrodeposition for 80 min.

[0043] Figure 5 It is a schematic diagram of the operation for detecting using a gas sensor.

[0044] Figure 6 It is a crystal diffraction experimental result diagram of modified zinc oxide.

[0045] Figure 7A It is a test result diagram of the continuous reaction characteristics of modified zinc oxide (time - current curve).

[0046] Figure 7B It is a diagram of the response time and recovery relationship of modified zinc oxide to a specific isopropanol.

[0047] Figure 7C It is a bar chart of the continuous reaction characteristics of modified zinc oxide.

[0048] Figure 7D It is a comparison result diagram of the repeatability test between multiple parallel electrodes of isopropanol on a modified zinc oxide electrode.

[0049] Figure 7E It is a repeatability test result diagram of isopropanol on a single modified zinc oxide electrode.

[0050] Figure 7F It is a graph of the selective test results for isopropanol volatile gas. Specific embodiments

[0051] The technical solution of the present invention will be further described below in conjunction with the accompanying drawings and through specific embodiments. However, the following examples are only simple examples of the present invention and do not represent or limit the scope of the claimed protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0052] For those not specifying specific techniques or conditions in the examples, they shall be carried out according to the techniques or conditions described in the literature in this field or according to the product specifications. For reagents or instruments not indicating the manufacturer, they are all conventional products that can be obtained by purchasing through regular channels.

[0053] Example 1

[0054] In this example, fecal samples of volunteers with a fixed weight were weighed, the volatile gases released from the headspace were collected, adsorbed by a solid-phase extraction needle, and then detected by a gas chromatography-mass spectrometer (the operation schematic diagram is as Figure 1 shown), so as to determine the signature gases of different volunteer categories. The volunteers included an adenoma group (2 people), a non-cancer group (4 people), and a colorectal cancer group (22 people). The non-cancer group was used as the control group or the healthy group.

[0055] An Agilent ultra-inert chromatographic column DB-624 was used. Its main component is a medium-polarity chromatographic column (6%, cyanopropyl / phenyl, 94% polydimethylsiloxane). Under the Figure 1 gas collection technical solution shown, the integration of the gas chromatography peak area was carried out. The integration of isopropanol was carried out according to the conditions where the target ion mass-to-charge ratios were 45, 43, 27, and 29 respectively; for the target gas p-cresol, the integration of the peaks with target ion mass-to-charge ratios of 107, 108, 77, and 79 was carried out.

[0056] First, a standard curve was established (the operation schematic diagram is as Figure 2 shown). By dropping standard products of isopropanol and p-cresol, the analysis and integration by a gas chromatography-mass spectrometer were carried out through a solid-phase extraction column. The results are as Figure 3As shown, Figure A shows the response graphs of isopropanol in a gas chromatograph-mass spectrometer at concentration ranges of 0.112 ppb, 1.12 ppb, 11.2 ppb, 28.0 ppb, and 58.0 ppb, and Figure B shows its fitting equation and linear range. Correspondingly, Figure C shows the response spectra of p-cresol in the range of 0.0104 ppb, 0.0520 ppb, 0.104 ppb, 0.520 ppb, and 1.04 ppb, and Figure D shows the corresponding peak area fitting equation and linear range. The corresponding detection limits obtained are as follows: isopropanol 0.923 ppb and p-cresol 0.0591 ppb. Their corresponding lowest detection concentrations are 2.50 ppb and 0.153 ppb.

[0057] Using 200 mg of fecal samples, after adsorbing for 20 minutes with a solid-phase extraction adsorption column, it was transferred to a gas chromatograph-mass spectrometer for qualitative and quantitative analysis. Analysis was carried out according to the adjusted retention time and the Agilent chromatographic analysis spectrum software, and qualitative and quantitative analysis of the headspace gas of different volunteer groups was carried out. The results are shown in Table 1. The average values of the headspace gas concentrations corresponding to 21 colorectal cancer patients are as follows: isopropanol 3.061 ± 0.589 and p-cresol 0.151 ± 0.177. For the corresponding adenoma gas markers, isopropanol is 0.448 ± 0.256 and p-cresol is 0.05440 ± 0.0190. For the gas markers in the healthy group, isopropanol is 0.448 ± 0.256 and p-cresol is 0.05440 ± 0.0190. It was found that isopropanol and p-cresol are headspace gases with good specificity in colorectal cancer, and their contents in the fecal headspace gas of colorectal cancer patients are significantly increased, which can be used as effective biomarker gases for distinguishing colorectal cancer from non-cancer groups and adenomas.

[0058] Table 1 Gas Chromatograph-Mass Spectrometer Coupled Detection Method

[0059]

[0060] Example 2

[0061] In this example, an isopropanol detection sensor was prepared.

[0062] On the surface of a 100-nm-thick gold electrode prepared by a sensing micro-nano processing platform, zinc oxide was grown by electrochemical deposition. 8 mM zinc nitrate hexahydrate was configured as the precursor, and 16 mM potassium chloride was used as the electrolyte to enhance the ionic strength. The following equation mechanism was used for the electrodeposition of zinc oxide:

[0063] 2Zn 2+ +O2 + 4e - →2ZnO

[0064] Electrodeposition was carried out using the constant voltage method, between -1.4V and -1.6V, with a silver / silver chloride reference electrode, and the temperature of the electrodeposition electrolyte was between 65 - 95°C. The electrodeposition time was controlled between 10 min and 80 min for optimization. After electrodeposition, a calcination method was used, calcining at 400°C for 30 min with a heating rate of 2°C / min.

[0065] The morphology of the prepared zinc oxide was detected using a scanning electron tunneling microscope and a transmission electron microscope, and the results are as Figure 4 shown. Among them, Figures A, E, and I are the morphologies of zinc oxide prepared by electrodeposition for 10 min, Figures B, F, and J are the morphologies of zinc oxide prepared by electrodeposition for 20 min, Figures C, G, and K are the morphologies of zinc oxide prepared by electrodeposition for 40 min, and Figures D, H, and L are the morphologies of zinc oxide prepared by electrodeposition for 80 min. In terms of its crystal structure, three-dimensional morphologies in various dimensions are shown. Intuitively, it can be observed that the morphological characteristics of zinc oxide gradually tend to be dense and thick, and its thicknesses are 3.65 ± 0.314 μm, 9.26 ± 0.710 μm, 90.5 ± 0.710 μm, and 187.0 ± 13.8 μm for electrodeposition times of 10 min, 20 min, 40 min, and 80 min, respectively.

[0066] A detection sensor was constructed using the prepared zinc oxide material:

[0067] Electrochemical deposition of ZnO was carried out in an 8 mmol / L aqueous solution of Zn(NO3)2·6H2O (as a precursor) and 16 mmol / L KCl (as an electrolyte), and its electrodeposition mechanism is as shown in the above equation. The electrochemical cell consisted of a traditional three-electrode system (a gold working electrode, a platinum rectangular sheet as a counter electrode, and Ag / AgCl (3 mol / L KCl) as a reference electrode). The three-electrode glass chamber was heated by a hot plate to control the temperature. The ZnO thin film was electrodeposited at an applied potential of -1.4V relative to Ag / AgCl. The deposition temperature was kept constant at 70°C. After electrodeposition for 10, 20, 40, and 80 min, the formed ZnO / Au heterojunction material junctions were thoroughly rinsed with distilled water and calcined at 400°C for 30 min with a heating rate of 2°C / min. Since the conductivity of the calcined gold electrode and the ZnO thin film was weak, a sputtering system was used to coat platinum nanoparticles in the control area to reconnect the ZnO thin film and the sputtered platinum area. After the coating step, with the help of sputtered platinum, a multimeter could test the resistance of ZnO and confirm the circuit connection.

[0068] The constructed sensor was used for isopropanol detection (the operation schematic diagram is as Figure 5As shown in the figure, the cavity of a 250 mL glassware with the model number GL-80 is used as the detection cavity. Crystal diffraction experiments are carried out on zinc oxide obtained at different electrodeposition times to obtain the differences in crystal structures at different electrodeposition times. According to the gas detection results analysis ( Figure 6 ), zinc oxide electrodeposited for 40 min has the best isopropanol response effect and relatively short regeneration time, which depends on its preferred lattice of (-1, 0, 0), (0, 0, -2), and (-1, 0, -1). The crystal diffraction result of the 40 min electrodeposition shows more obvious crystal response at (-1, 0, -1) compared with the crystals in these three crystal states. The copper observed in the 40 min crystal diffraction is due to the substrate used in the characterization, not the components added to the sample.

[0069] Further analyze the detection performance of the sensor, specifically including the following experimental procedures:

[0070] Use Figure 5 the platform shown in the figure to construct a detection example of the sensor. Place the constructed sensor in a 250 mL GL-80 cavity, and add isopropanol with different concentrations for performance testing. The bottom hot plate is heated at 80 °C to maintain the internal temperature of the cavity at 40 °C for all concentration tests. Isopropanol follows a regular feedback from 1.17 ppm to 117 ppm. At higher concentrations, its feedback gradually tends to saturation and cannot provide a linear feedback ability. Through this experimental procedure, Figure 7B the feedback response time and desorption images are obtained, as well as Figure 7C the results of the response bar chart. In addition, the results of intra-group repeatability experiments and inter-group repeatability experiments are also tested ( Figure 7D ). And Figure 7E the selectivity test results are carried out using the concentrations of interfering substances determined by gas chromatography-mass spectrometry.

[0071] The results are as Figures 7A - 7F shown. Figure 7A It is the test result (time-current curve) of the continuous reaction characteristics of the modified oxidant, and the results show that within a certain range, the current increases with the increase in the concentration of the detected isopropanol gas (from 1.17 ppm to 234 ppm), and when detecting 351 ppm of isopropanol gas, the electrical signal weakens, indicating that the adsorption capacity of this material reaches saturation in an isopropanol environment of 351 ppm. Figure 7B It is the response time and recovery relationship diagram of the modified zinc oxide to a specific isopropanol. The results show that the zinc oxide responds to 117 ppm of isopropanol after 410 s and desorbs the gas after 210 s; Figure 7C It is the bar chart of the continuous reaction characteristics of the modified zinc oxide, and the results show that there is a proportional linear relationship between the electrical signal and the concentration of the detected gas; Figure 7DIt is a graph showing the results of repeated tests between multiple parallel electrodes of isopropanol on a modified zinc oxide electrode. The results indicate that the zinc oxide gas sensor prepared by the above preparation method has high sensitivity and can maintain high sensitivity in mass production; Figure 7E It is the result of repeated tests of isopropanol on a single electrode of a modified zinc oxide electrode, indicating that the zinc oxide sensor has a lifespan of at least one month and can be reused; Figure 7F It is a graph showing the results of selectivity tests of isopropanol volatile gas. The results indicate that electroplated zinc oxide has poor response to other gases volatilized in feces, thus having good selectivity, and the result accuracy is not interfered by other gases.

[0072] Example 3

[0073] In this example, isopropanol and p-cresol are used for colorectal cancer diagnosis and the diagnostic efficacy is verified.

[0074] With the verification of 22 fecal samples with unknown colorectal cancer, the headspace gas of feces was analyzed using the sensor prepared in Example 2, and diagnosis was carried out based on the isopropanol results. The specific diagnostic criteria are as follows: for colorectal cancer, the isopropanol sensor signal of cancer patients / healthy people ≥ 2:1; then pathological section examination was performed on volunteers. This set ratio conforms to the pathological section diagnosis results. The accuracy, sensitivity, and specificity of the diagnosis based on isopropanol were 94.4%, 99.9%, and 99.9% respectively when compared with the corresponding pathological section results.

[0075] The p-cresol content of the above samples was detected by gas chromatography-mass spectrometry, and diagnosis was carried out based on the p-cresol results. The specific diagnostic criteria are as follows: when the p-cresol concentration (C p-cresol ) of cancer patients / healthy people ≥ 50:1, the diagnosis result is adenoma; when the p-cresol concentration of cancer patients / healthy people ≥ 77:1, the diagnosis result is colorectal cancer. When the diagnosis results based on p-cresol were compared with the corresponding pathological section results, the accuracy, sensitivity, and specificity of the diagnosis based on p-cresol were 78.6%, 79.9%, and 79.9% respectively.

[0076] In summary, the present invention uses gas chromatography-mass spectrometry to locate the headspace marker gases of fecal samples of colorectal cancer volunteers, non-cancer groups, and adenoma groups, excavates biomarker for colorectal cancer diagnosis, provides new ideas for colorectal cancer diagnosis, further combines this tumor gas biomarker, designs and detects sensors, realizes the crystal growth and exposure of polycrystalline state in the Z-axis direction by adjusting relevant parameters in the electrochemical deposition process. The relevant exposed crystals have a good effect on the catalytic oxidation of the headspace gas biomarker of colorectal cancer, can achieve rapid and accurate detection, and have simple operation and low cost, providing a new tool for the diagnosis of colorectal cancer and having important application value.

[0077] The applicant declares that the above description is only a specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the protection scope and the disclosure scope of the present invention.

Claims

1. A biomarker for detecting colorectal cancer, characterized in that: The biomarkers include isopropanol and / or p-cresol.

2. The biomarker for detecting colorectal cancer according to claim 1, characterized in that: The biomarkers include isopropanol and / or p-cresol in the headspace gas of stool samples.

3. Use of the biomarker for detecting colorectal cancer and / or its detection reagent as described in claim 1 in the preparation of auxiliary diagnosis or diagnostic products for colorectal cancer.

4. A gas sensor, characterized in that: The gas sensor includes zinc oxide; The zinc oxide has lattices of (-1, 0, 0), (0, 0, -2) and (-1, 0, -1); The gas detected by the gas sensor includes the biomarker for detecting colorectal cancer as described in claim 1.

5. The gas sensor according to claim 4, characterized in that: The gas sensor further includes at least one of a breadboard, a plug-in wire, a solderless jumper wire, an amplifier circuit or an analog-to-digital conversion unit; Preferably, the breadboard is used for connection with the sensor, the plug wire is used for connection with the downstream amplification circuit, and the analog-to-digital conversion unit is used for outputting the signal at the end.

6. The method for preparing a gas sensor according to claim 4, characterized in that: The preparation method comprises: preparing zinc oxide, and using the zinc oxide to prepare a gas sensor; The method for preparing zinc oxide comprises: using zinc ions as raw materials for electrochemical deposition.

7. The method for preparing a gas sensor for colorectal cancer diagnosis according to claim 6, characterized in that: The electrochemical deposition time is 10 to 80 minutes, preferably 30 to 50 minutes, and more preferably 35 to 45 minutes; Preferably, the electrochemical deposition adopts a constant voltage, the voltage is -1.6V to -1.4V; Preferably, the reference electrode for electrochemical deposition is silver / silver chloride; Preferably, the electrolyte for electrochemical deposition comprises a potassium chloride solution; Preferably, the temperature of the electrolyte is 65-95°C; Preferably, the electrochemical deposition further comprises a calcination step; Preferably, the calcination conditions include: calcination at 400-500° C. for 30-60 min, and a heating rate of 2-2.5° C. / min.

8. A method for detecting isopropanol, characterized in that: The detection method comprises: performing detection using the gas sensor according to claim 4 or 5.

9. A device for diagnosing colorectal cancer, characterized in that: The device comprises: A detection unit, used to detect the content of the biomarker for detecting colorectal cancer according to claim 1 in the headspace gas of the sample to be tested; The analysis unit is used to make a determination using the content of the biomarker detected by the detection unit.

10. The device for diagnosing colorectal cancer according to claim 9, characterized in that: The sample to be tested includes a stool sample; Preferably, the detection method comprises using the gas sensor according to claim 4 or 5 for detection, and / or performing gas chromatography-mass spectrometry detection; Preferably, the criteria for determining colorectal cancer positivity include: isopropanol ≥ 1.0 ppb, and / or, p-cresol ≥ 0.055 ppb.

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