Method for establishing quantitative prediction model of endogenous VOCs (Volatile Organic Compounds) in exhaled air of human body

Abstract

The invention relates to a method for establishing a quantitative prediction model of endogenous VOCs (Volatile Organic Compounds) in expired gas of a human body, which comprises the following steps of: determining the type of the endogenous VOCs in the expired gas of the human body and the normal value range of each type of endogenous VOCs in the expired gas of the human body by establishing the quantitative prediction model; when the to-be-analyzed human body exhaled gas exists, pretreating the human body exhaled gas to obtain ionized soft ionization gaseous molecules; analyzing the ionized soft ionization gaseous molecules through a carbon dioxide isotope internal standard quantification method to obtain a predetermined content value of the type of the endogenous VOCs in the to-be-analyzed human exhaled gas, wherein the content value of the type of the endogenous VOCs in the to-be-analyzed human exhaled gas is determined; and according to a comparison result of each predetermined content value of the endogenous VOCs in the exhaled air of the human body and the corresponding normal value range, judging an abnormal condition. According to the mode, a final result can be obtained only by analyzing the ionized soft ionization gaseous molecules through a carbon dioxide isotope internal standard quantitative method, and the whole process is simple and efficient.

Description

Technical Field

[0001] The present invention relates to the technical field related to gas composition prediction, and in particular to a method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath. Background Art

[0002] Endogenous compounds in human exhaled breath, including inorganic gases (such as NO and CO) and VOCs (such as isoprene, ethane, pentane, acetone), are metabolites of human tissues. By analyzing the components and predicting the concentrations of endogenous markers, relevant information on human tissue metabolism and health status can be obtained non-invasively, which helps to clarify the corresponding physiological processes, disease occurrence, disease progression, and pharmacological responses.

[0003] At present, the quantitative analysis of endogenous VOCs in human exhaled breath is performed based on the breath diagnosis technology of gas chromatography. This method is cumbersome to operate, requires a lot of resources, and is inefficient. The main disadvantages of the breath diagnosis technology based on gas chromatography are the lack of dynamics and difficulty in quantification. Breathing is a dynamic process. The currently reported analysis methods are mostly static, and quantitative determination is difficult. The quantitative method and accurate determination of endogenous markers need further research. Summary of the invention

[0004] The purpose of the present invention is to solve at least one of the deficiencies of the prior art and to provide a method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions: Specifically, a method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath is proposed, including the following: Determine the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath; When there is human exhaled air to be analyzed, Pre-treating the human exhaled air to obtain ionized and soft-ionized gaseous molecules; The soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method to obtain the content value of the predetermined type of endogenous VOCs in the human exhaled breath to be analyzed; The abnormality is determined based on the comparison results of each predetermined content value of endogenous VOCs in human exhaled breath with the corresponding normal value range.

[0006] Further, specifically, the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath are determined as follows: Through preliminary experiments, molecular ion peaks were identified and identified based on samples from the healthy population using relevant equipment, and quantitative analysis was performed using the standard gas external standard method. A data array was established for the content and relative proportion of common endogenous VOCs in the human body, and SIMCA-P was used to perform principal component analysis and partial least squares analysis to find out the corresponding characteristics of exhaled breath. Regression analysis and cluster analysis were then used to verify the data, and cross-validation was performed for final determination.

[0007] Further, specifically, the preprocessing operation includes: The exhaled air of the human body is input into the flow-through medium channel discharge source to output soft ionized gas molecules; The soft ionized gaseous molecules are input into the GC-MS device for ionization to obtain ionized soft ionized gaseous molecules.

[0008] Further, specifically, the soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method, including: The carbon dioxide isotope peak used for quantification of endogenous markers is determined by preliminary experiments; By comparing the input data after ionization with the abundance of each endogenous marker, the isotope peak with a peak intensity close to that of the endogenous marker in exhaled breath was selected as the reference standard, and the relative ratios of different markers to the carbon dioxide isotope peak were analyzed for quantification.

[0009] Further, specifically, the process of determining the abnormal situation includes: Determine whether the content value of each predetermined endogenous VOCs in human exhaled breath is within its corresponding normal value range. If so, mark it as normal; if not and above the normal value range, mark it as abnormally high; if not and below the normal value range, mark it as abnormally low.

[0010] The present invention also proposes a quantitative prediction system for endogenous VOCs in human exhaled breath, which uses a quantitative prediction model established by the method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath, including: The test data acquisition module is used to acquire the exhaled gas of the target human body; The soft ionization module is constructed based on a flow-through medium channel discharge source and is used to softly ionize the target human exhaled gas to obtain soft ionized gaseous molecules; The ionization module is built on the basis of GC-MS equipment and is used to ionize soft ionized gaseous species; A model calling module is used to process the ionized soft ionized gaseous molecules through the quantitative prediction model to obtain prediction results; The visualization module is used to visualize the prediction results.

[0011] Among them, the flow-through medium channel discharge source is integrated with the GC-MS equipment.

[0012] Further, specifically, visually displaying the prediction results includes: The name of each endogenous marker, the corresponding content value and the abnormal analysis situation are associated and visualized in the form of a chart.

[0013] The beneficial effects of the present invention are: The present invention proposes a method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath. By establishing a quantitative prediction model, the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath are determined; when there is human exhaled breath to be analyzed, the human exhaled breath is pretreated to obtain ionized soft ionized gaseous molecules; the ionized soft ionized gaseous molecules are analyzed by a carbon dioxide isotope internal standard quantitative method to obtain the content value of the type of endogenous VOCs in human exhaled breath predetermined in the human exhaled breath to be analyzed; and the abnormal situation is judged according to the comparison result of the content value of each predetermined endogenous VOCs in human exhaled breath with the corresponding normal value range. This method only needs to perform a carbon dioxide isotope internal standard quantitative method to analyze the ionized soft ionized gaseous molecules to obtain the final result, and the whole process is simple and efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The above and other features of the present disclosure will become more apparent by describing in detail the embodiments shown in the accompanying drawings. The same reference numerals in the accompanying drawings of the present disclosure represent the same or similar elements. Obviously, the accompanying drawings described below are only some embodiments of the present disclosure. For those skilled in the art, other accompanying drawings can be obtained based on these accompanying drawings without creative work. In the accompanying drawings: Figure 1 Shown is a flow chart of a method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath according to the present invention. DETAILED DESCRIPTION

[0015] The following will be combined with the embodiments and drawings to clearly and completely describe the concept, specific structure and technical effects of the present invention, so as to fully understand the purpose, scheme and effect of the present invention. It should be noted that the embodiments in this application and the features in the embodiments can be combined with each other without conflict. The same reference numerals used throughout the drawings indicate the same or similar parts.

[0016] Example 1, reference Figure 1 The present invention proposes a method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath, comprising the following steps: Step 110, determining the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath; Step 120: When there is human exhaled air to be analyzed, Step 130, pre-treating the human exhaled air to obtain ionized and soft-ionized gaseous molecules; Step 140, analyzing the ionized soft ionized gaseous molecules by carbon dioxide isotope internal standard quantitative method to obtain the content value of the predetermined type of endogenous VOCs in the human exhaled breath to be analyzed; Step 150: determine the abnormality of each predetermined endogenous VOCs content in human exhaled breath according to the comparison result with the corresponding normal value range.

[0017] In the present embodiment 1, by establishing a quantitative prediction model, the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath are determined; when there is human exhaled breath to be analyzed, the human exhaled breath is pretreated to obtain ionized soft ionized gaseous molecules; the ionized soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method to obtain the content value of the predetermined type of endogenous VOCs in human exhaled breath to be analyzed; according to the comparison result of each predetermined content value of endogenous VOCs in human exhaled breath with the corresponding normal value range, its abnormal situation is judged. This method only needs to use the carbon dioxide isotope internal standard quantitative method to analyze the ionized soft ionized gaseous molecules to obtain the final result, and the whole process is simple and efficient.

[0018] As a preferred embodiment of the present invention, specifically, the method for determining the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath is: Through preliminary experiments, molecular ion peaks were identified and identified based on samples from the healthy population using relevant equipment, and quantitative analysis was performed using the standard gas external standard method. A data array was established for the content and relative proportion of common endogenous VOCs in the human body, and SIMCA-P was used to perform principal component analysis and partial least squares analysis to find out the corresponding characteristics of exhaled breath. Regression analysis and cluster analysis were then used to verify the data, and cross-validation was performed for final determination.

[0019] In this preferred embodiment, the 100 breath samples collected were first classified according to the research cohort, and the molecular ion peaks were identified and identified using the analysis software provided by the instrument, and quantitative analysis was performed using the standard gas external standard method. The content and relative proportion of common endogenous VOCs in the human body were studied, and a data array was established using control samples.

[0020] In order to organically combine breath analysis data with actual samples, multivariate statistical methods are an effective means of mathematical statistics, especially suitable for the analysis of complex high-throughput data, and are increasingly used in the study of breath characteristics. At present, the statistical methods involved include principal component analysis, cluster analysis, discriminant analysis, partial least squares analysis, etc., and the statistical analysis software involved includes SIMCA-P, SPSS, R, SAS, MATLAB, etc. This project intends to use SIMCA-P for principal component analysis and partial least squares analysis to find the corresponding characteristic substances of breath, and then use regression analysis and cluster analysis for data verification, and combine multiple statistical methods and statistical software for cross-validation to obtain more accurate and reliable analysis results.

[0021] Through data comparison and analysis, we finally screened out the characteristic endogenous VOCs in human exhaled breath and the relative content range of each compound, established an analysis model, and carried out experimental verification to determine the accuracy and sensitivity of the screening model. We established a dynamic, wide-range quantitative analysis method for exhaled VOCs based on "SOFT IONIZATION + DIRECT MASS".

[0022] As a preferred embodiment of the present invention, specifically, the pretreatment operation includes: The exhaled air of the human body is input into the flow-through medium channel discharge source to output soft ionized gas molecules; The soft ionized gaseous molecules are input into the GC-MS device for ionization to obtain ionized soft ionized gaseous molecules.

[0023] As a preferred embodiment of the present invention, specifically, the soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method, including: The carbon dioxide isotope peak used for quantification of endogenous markers is determined by preliminary experiments; By comparing the input data after ionization with the abundance of each endogenous marker, the isotope peak with a peak intensity close to that of the endogenous marker in exhaled breath was selected as the reference standard, and the relative ratios of different markers to the carbon dioxide isotope peak were analyzed for quantification.

[0024] As a preferred embodiment of the present invention, specifically, the process of determining the abnormal situation includes: Determine whether the content value of each predetermined endogenous VOCs in human exhaled breath is within its corresponding normal value range. If so, mark it as normal; if not and above the normal value range, mark it as abnormally high; if not and below the normal value range, mark it as abnormally low.

[0025] Embodiment 2, the present invention further proposes a quantitative prediction system for endogenous VOCs in human exhaled breath, which uses the quantitative prediction model established by the method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath, including: The test data acquisition module is used to acquire the exhaled gas of the target human body; The soft ionization module is constructed based on a flow-through medium channel discharge source and is used to softly ionize the target human exhaled gas to obtain soft ionized gaseous molecules; The ionization module is built on the basis of GC-MS equipment and is used to ionize soft ionized gaseous species; A model calling module is used to process the ionized soft ionized gaseous molecules through the quantitative prediction model to obtain prediction results; The visualization module is used to visualize the prediction results.

[0026] Among them, the flow-through medium channel discharge source is integrated with the GC-MS equipment.

[0027] In this embodiment 2, it is considered that soft ionization is a technique used in mass spectrometry, which is characterized by using relatively low energy to convert molecules into ions or fragments, thereby reducing the generation of molecular fragments. This process makes the peaks in the mass spectrum generally simpler and easier to analyze and identify. The ionization source used in this scheme is a flow-through medium channel discharge source (SICRIT®), which only uses the electrode discharge to instantly excite and ionize the gaseous chemical substances on the flow path at the inlet end of the mass spectrometer to identify the chemical composition and form of the inflowing material in real time, without the need to use solvents (like the traditional liquid mass-dependent ESI) to rely on solvents and any auxiliary gases, directly achieving rapid, broad-spectrum, sensitive, high-throughput accurate quantitative, qualitative, traceability, screening, or cluster analysis. The ion source can be used at room temperature and pressure, directly and continuously soft ionizes gaseous organic small molecules online, and maintains complete molecular ion information. There is basically no need for sample preparation, the sample analysis time is short (within 1 second), and it is applicable to high throughput.

[0028] By connecting the ionization source in series with a GC-MS and modifying and assembling the instrument, rapid ionization and analysis of gaseous small molecules can be achieved. High-resolution testing and analysis are performed using known endogenous volatile organic compounds commonly found in human exhaled breath as reference substances, and instrument parameters (such as ionization energy) are adjusted to optimize the sensitivity of the instrument.

[0029] The soft ionization source is connected in series with a small mobile portable mass spectrometer to reduce the size of the equipment. After modification, the ionization source, mass spectrometer, power supply, etc. are integrated into a device the size of a suitcase. The equipment can be directly connected to a laptop or tablet (with data analysis software installed). After commercialization, the equipment can be carried to various application scenarios.

[0030] As a preferred embodiment of the present invention, specifically, visually displaying the prediction results includes: The name of each endogenous marker, the corresponding content value and the abnormal analysis situation are associated and visualized in the form of a chart.

[0031] Although the description of the present invention has been quite detailed and specifically describes several described embodiments, it is not intended to be limited to any of these details or embodiments or any particular embodiment, but should be regarded as providing a broad possible interpretation of these claims in view of the prior art by reference to the appended claims, thereby effectively covering the intended scope of the present invention. In addition, the above description of the present invention is based on the embodiments foreseeable by the inventor, and its purpose is to provide a useful description, and those non-substantial changes to the present invention that have not yet been foreseen may still represent equivalent changes to the present invention.

[0032] The above is only a preferred embodiment of the present invention. The present invention is not limited to the above implementation. As long as the technical effect of the present invention is achieved by the same means, it should belong to the protection scope of the present invention. Within the protection scope of the present invention, its technical scheme and / or implementation method can have various modifications and changes.

Claims

1. A method for establishing a quantitative prediction model for endogenous VOCs in human exhaled breath, characterized in that: Includes the following: Determine the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath; When there is human exhaled air to be analyzed, Pre-treating the human exhaled air to obtain ionized and soft-ionized gaseous molecules; The soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method to obtain the content value of the predetermined type of endogenous VOCs in the human exhaled breath to be analyzed; The abnormality is determined based on the comparison results of each predetermined content value of endogenous VOCs in human exhaled breath with the corresponding normal value range.

2. The method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath according to claim 1, characterized in that: Specifically, the types of endogenous VOCs in human exhaled breath and the normal value range of each endogenous VOCs in human exhaled breath are determined as follows: Through preliminary experiments, molecular ion peaks were identified and identified based on samples from the healthy population using relevant equipment, and quantitative analysis was performed using the standard gas external standard method. A data array was established for the content and relative proportion of common endogenous VOCs in the human body, and SIMCA-P was used to perform principal component analysis and partial least squares analysis to find out the corresponding characteristics of exhaled breath. Regression analysis and cluster analysis were then used to verify the data, and cross-validation was performed for final determination.

3. The method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath according to claim 1, characterized in that: Specifically, the preprocessing operation includes: The exhaled air of the human body is input into the flow-through medium channel discharge source to output soft ionized gas molecules; The soft ionized gaseous molecules are input into the GC-MS device for ionization to obtain ionized soft ionized gaseous molecules.

4. The method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath according to claim 1, characterized in that: Specifically, the soft ionized gaseous molecules are analyzed by the carbon dioxide isotope internal standard quantitative method, including: The carbon dioxide isotope peak used for quantification of endogenous markers is determined by preliminary experiments; By comparing the input data after ionization with the abundance of each endogenous marker, the isotope peak with a peak intensity close to that of the endogenous marker in exhaled breath was selected as the reference standard, and the relative ratios of different markers to the carbon dioxide isotope peak were analyzed for quantification.

5. The method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath according to claim 1, characterized in that: Specifically, the process of determining the abnormal situation includes: Determine whether the content value of each predetermined endogenous VOCs in human exhaled breath is within its corresponding normal value range. If so, mark it as normal; if not and above the normal value range, mark it as abnormally high; if not and below the normal value range, mark it as abnormally low.

6. A quantitative prediction system for endogenous VOCs in human exhaled breath, characterized in that: A quantitative prediction model established by using the method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath as described in any one of claims 1 to 5, comprising: The test data acquisition module is used to acquire the exhaled gas of the target human body; The soft ionization module is constructed based on a flow-through medium channel discharge source and is used to softly ionize the target human exhaled gas to obtain soft ionized gaseous molecules; The ionization module is built on the basis of GC-MS equipment and is used to ionize soft ionized gaseous species; A model calling module is used to process the ionized soft ionized gaseous molecules through the quantitative prediction model to obtain prediction results; A visualization module, used for visualizing the prediction results; Among them, the flow-through medium channel discharge source is integrated with the GC-MS equipment.

7. The method for establishing a quantitative prediction model of endogenous VOCs in human exhaled breath according to claim 5, characterized in that: Specifically, visually displaying the prediction results includes: The name of each endogenous marker, the corresponding content value and the abnormal analysis situation are associated and visualized in the form of a chart.

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