CN112067712B - Volatile marker for diagnosing novel coronavirus and application thereof - Google Patents
Volatile marker for diagnosing novel coronavirus and application thereof Download PDFInfo
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- CN112067712B CN112067712B CN202010832686.6A CN202010832686A CN112067712B CN 112067712 B CN112067712 B CN 112067712B CN 202010832686 A CN202010832686 A CN 202010832686A CN 112067712 B CN112067712 B CN 112067712B
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Abstract
The invention relates to a volatile marker for diagnosing novel coronavirus and application thereof, wherein the marker is derived from metabolism of the novel coronavirus, and the marker refers to a combination of a plurality of or all of the following volatile organic compounds: styrene, acetoin, 2,4, 6-trimethylpyridine, 3-methyltridecane, tetradecane, isooctanol, pentadecane, hexadecane and 1-methylene-1H-indene, wherein the diagnostic reagent is used for diagnosing the novel coronavirus by detecting the content of the volatile marker in the exhaled air of a tested person. The invention provides a plurality of volatile organic compounds generated by metabolism of novel coronavirus as markers for breath diagnosis of novel coronavirus infection, and the application prospect in novel coronavirus screening is wide.
Description
Technical Field
The invention relates to the technical field of novel coronavirus detection, in particular to a volatile marker for diagnosing novel coronavirus and application thereof.
Background
The novel coronavirus pneumonia, called 'Xinguan pneumonia' for short, is a kind of acute infectious diseases and is caused by 2019 novel coronavirus (COVID-19) infection. After a person is infected with the novel coronavirus, the main symptoms include respiratory symptoms, fever, cough, shortness of breath, dyspnea, etc., and in more severe cases, the infection may cause pneumonia, severe acute respiratory syndrome, renal failure, and even death. At present, aiming at diseases caused by novel coronavirus, effective antiviral drugs aiming at pathogens are lacked, and isolation treatment and symptomatic support treatment are mainly used. Therefore, the method is the best way to overcome the new coronavirus by rapidly screening and effectively isolating the susceptible population of the new coronavirus. At present, the existing detection method mainly adopts nucleic acid detection, but the method has inconvenient sampling, long detection time and still has unsatisfactory detection effect. Therefore, if the rapid detection is realized, the method has extremely important practical significance and social significance.
Research finds that when the novel coronavirus is propagated in vivo in a large quantity, volatile metabolites can be generated and are exhausted out of the body along with the exhaled air of the human body, so that novel coronavirus diagnosis can be realized through the novel coronavirus volatile marker in the exhaled air of the human body. In addition, compared with the existing nucleic acid detection, the method also has the advantages of rapid sample collection, low risk and the like.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a volatile marker for diagnosing novel coronavirus.
Yet another object of the present invention is to: provides the application of the volatile marker in breath detection.
The purpose of the invention is realized by the following technical scheme: a volatile marker for diagnosing a novel coronavirus comprising: more than two or all of volatile organic compounds such as styrene, acetoin, 2,4, 6-trimethyl pyridine, 3-methyltridecane, tetradecane, isooctanol, pentadecane, hexadecane and 1-methylene-1H-indene.
The principle of the invention is as follows: the new coronaviruses produce specific compounds in vivo, some of which are expelled from the body with the exhaled air.
The invention also provides an application of the volatile marker for diagnosing the novel coronavirus, which is used for diagnosing the infection condition of the novel coronavirus by detecting the content of the diagnostic marker in exhaled air of a tested person, and when at least 2 of 2,4, 6-trimethylpyridine, tetradecane, isooctanol and pentadecane are detected in the exhaled air and 3-methyltridecane and styrene exist, the tested person is confirmed not to be infected with the novel coronavirus; when at least two of 2,4, 6-trimethylpyridine, tetradecane, isooctanol, pentadecane are detected in exhaled breath, and one of acetoin and 1-methylene-1H-indene is present, it is confirmed that the subject has been infected with the novel coronavirus.
The invention can provide a rapid and effective novel coronavirus diagnosis method by screening volatile metabolites of the novel coronavirus.
Further, the detection is to detect the content of the novel coronavirus diagnostic marker in the exhaled breath of the tested person by a mass spectrometry analysis method.
The invention also provides specific analytical methods as shown in the examples. Can be used for rapid diagnosis of novel coronavirus.
The invention relates to a volatile marker for diagnosing novel coronavirus, which is derived from a novel coronavirus metabolite, a marker screening sample is derived from a novel coronavirus culture solution, and the collected novel coronavirus culture solution sample is delivered to a gas chromatography-mass spectrometer for detecting the content of the volatile marker after being subjected to sample introduction by a headspace sample introduction device and concentration by a solid phase micro-extraction device.
Compared with the prior art, the invention has the following beneficial effects;
1. the detection method has the advantages of rapid sample collection, non-invasiveness and low risk.
2. The screened novel coronavirus volatile markers have multiple types, and the accuracy of a diagnosis result is ensured to be high by detecting multiple marker indexes.
3. The selected marker has significant difference between the novel coronavirus group and the contrast, so that the diagnostic effect is accurate and reliable.
Drawings
FIG. 1 is a chromatogram of the volatile marker species and gas chromatography-mass spectrum of the novel coronavirus;
other features, objects and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments thereof, which proceeds with reference to the accompanying drawings.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Example 1
Collection of samples
1) 2 ml of culture medium samples are collected from 10 culture bottles in which lung epithelial cells and novel coronavirus are cultured respectively, 20 samples are respectively put into the sample bottles, the sample amount is accurately controlled to be 1 ml, and the samples are heated for 20 minutes to 80 ℃ to ensure that steam reaches chemical equilibrium;
2) Connecting a headspace sampling device to a solid phase micro-extraction device, and pre-concentrating the marker in the sample by a solid phase micro-extraction head with a 75-micron CAR/PDMS coating;
3) Pre-concentrating VOCs in the sample for 30 minutes respectively;
4) GC-MS gas chromatography and mass spectrometer analysis: carrying out instantaneous desorption on the extraction head at a GC-MS sample inlet and a high temperature of 280 ℃ for 1 minute, carrying out sample injection in a non-split-flow mode, opening a split-flow valve after 2 minutes, and carrying out chromatographic separation by using a CD-1MS chromatographic column with the diameter of 1.4 micrometers, the diameter of 60 meters and the diameter of 0.25 millimeter; temperature rising procedure: the initial temperature is 35 ℃, the retention time is 10 minutes, the temperature is raised to 200 ℃ at the speed of 8 ℃/min, the temperature is raised to 220 ℃ at the speed of 15 ℃/min, and the temperature is kept for 12 minutes; scanning the mass spectrometer in a full range of 42-400amu, wherein the electron bombardment energy is 70eV, the ion source temperature of the quadrupole mass spectrometer is 200 ℃, the carrier gas is high-purity helium, and the flow rate is 44.2 cm/s; the detected substances are preliminarily qualified by mass spectrometry with an NIST08 library, and the substances with the similarity of more than 90% are quantified by using a relative peak area;
5) When the existence of at least 2 of 2,4, 6-trimethylpyridine, tetradecane, isooctanol and pentadecane and the existence of 3-methyltridecane and styrene are detected in the volatilized gas, marking the subject not to be infected with the novel coronavirus; when the presence of at least 2 of 2,4,6-trimethylpyridine, tetradecane, isooctanol, pentadecane and 1 of acetoin and 1-methylene-1H-indene are detected in the exhaled breath, the subject is marked as infected with the novel coronavirus. As a result, 7 samples of non-novel coronavirus and 8 samples of novel coronavirus were found.
Example 2
Collection of samples
1) 2 ml of culture medium samples which are 20 parts of each culture medium sample and are required to be collected in 10 culture bottles respectively cultured with gastric mucosal epithelial cells and novel coronavirus are put into the sample bottles, the sample volume is accurately controlled to be 1 ml, and the samples are heated for 20 minutes to 80 ℃ to ensure that the steam reaches chemical equilibrium;
2) Connecting a headspace sampling device to a solid phase micro-extraction device, and pre-concentrating the marker in the sample by a solid phase micro-extraction head with a 75-micron CAR/PDMS coating;
3) Pre-concentrating VOCs in the sample for 30 minutes respectively;
4) GC-MS gas chromatography and mass spectrometer analysis: placing the extraction head at a GC-MS sample inlet, carrying out instantaneous desorption for 1 minute at the high temperature of 280 ℃, carrying out sample injection in a non-flow-dividing mode, opening a flow dividing valve after 2 minutes, and carrying out chromatographic separation by using a CD-1MS chromatographic column with the diameter of 1.4 micrometers, the diameter of 60 meters and the diameter of 0.25 millimeter; temperature rising procedure: the initial temperature is 35 ℃, the retention time is 10 minutes, the temperature rises to 200 ℃ at 8 ℃/min, the temperature rises to 220 ℃ at 15 ℃/min, and the temperature is kept for 12 minutes; scanning the mass spectrometer in a full range of 42-400amu, wherein the electron bombardment energy is 70eV, the ion source temperature of the quadrupole mass spectrometer is 200 ℃, the carrier gas is high-purity helium, and the flow rate is 44.2 cm/s; the detected substances are preliminarily qualified by mass spectrum with NIST08 library, and the substances with the similarity of more than 90% are quantified by using relative peak areas;
5) When the existence of at least 2 of 2,4, 6-trimethylpyridine, tetradecane, isooctanol, pentadecane and 3-methyltridecane and styrene are detected in the volatilized gas, marking the subject as not infected with the novel coronavirus; when the presence of at least 2 of 2,4,6-trimethylpyridine, tetradecane, isooctanol, pentadecane and 1 of acetoin and 1-methylene-1H-indene are detected in the exhaled breath, the subject is marked as infected with the novel coronavirus. As a result, 8 samples of non-novel coronavirus and 7 samples of novel coronavirus were found.
FIG. 1 is a new coronavirus volatility marker species and gas chromatography-mass spectrum diagram, wherein: the novel coronavirus culture solution (a) and the blank culture solution (b) have gas chromatography-mass spectrograms and corresponding volatile markers, and the names of the volatile markers are as follows:
Claims (1)
1. a volatile marker for diagnosing a novel coronavirus, comprising the following volatile organic compounds: styrene, acetoin, 2,4, 6-trimethylpyridine, 3-methyltridecane, tetradecane, isooctanol, pentadecane, hexadecane and 1-methylene-1H-indene.
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| CN113308560B (en) * | 2020-12-31 | 2023-07-07 | 郑州大学第一附属医院 | Oral microbial gene marker for noninvasive diagnosis of novel coronavirus infected patient and application thereof |
| CN113984948A (en) * | 2021-10-28 | 2022-01-28 | 上海交通大学 | Combined diagnosis model for helicobacter pylori infection based on VOC marker and establishment method and application thereof |
| CN115236220B (en) * | 2022-06-23 | 2023-12-19 | 上海交通大学 | Volatile marker for diagnosing novel coronavirus and application thereof |
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| CN1457777A (en) * | 2003-05-12 | 2003-11-26 | 中国人民解放军军事医学科学院毒物药物研究所 | New use of indole derivatives as anti-SARS medicine |
| CN105758966A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Metabolic marker group for diagnosing coronary heart disease |
| CN111411104A (en) * | 2020-03-30 | 2020-07-14 | 李长桂 | Magnetic bead for detecting neocoronal pneumonia and preparation method thereof |
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| US20050037338A1 (en) * | 2003-08-14 | 2005-02-17 | Kuo-Tang Tseng | Method and means for detection of severe acute respiratory syndrome |
| WO2007053165A2 (en) * | 2005-01-11 | 2007-05-10 | Yale University | Virus protein microarray and uses therefor |
| CN103940924B (en) * | 2014-04-14 | 2016-06-01 | 上海交通大学 | Cancer of the stomach gas mark in expiration is in the purposes prepared in stomach cancer diagnosis reagent |
| KR20170141732A (en) * | 2015-04-20 | 2017-12-26 | 사이넥시스 엘엘씨 | Clean room with dilute hydrogen peroxide (DHP) gas and its use |
| CN110045035B (en) * | 2019-04-30 | 2021-05-11 | 上海交通大学 | Gastric cancer VOC marker in saliva and application thereof in preparation of gastric cancer diagnostic reagent |
| CN211148670U (en) * | 2020-01-29 | 2020-07-31 | 兰州雅华生物技术有限公司 | Novel rapid detection kit for coronavirus 2019-nCoV antigen |
| CN111303297B (en) * | 2020-02-14 | 2021-08-31 | 中国人民解放军总医院 | Recombinant protein for detecting 2019 novel coronavirus antibody by double-antigen sandwich method, test strip, preparation method and application |
| CN111349720A (en) * | 2020-03-19 | 2020-06-30 | 中国医学科学院病原生物学研究所 | Nucleic acid reagent, kit, system and method for detecting respiratory tract infection virus |
| CN111323511B (en) * | 2020-03-26 | 2022-04-29 | 浙江大学医学院附属第四医院(浙江省义乌医院、浙江大学医学院附属第四医院医共体) | Rapid detection kit and method for inactivating new coronavirus |
| CN111378788B (en) * | 2020-04-08 | 2021-02-26 | 广州微远医疗器械有限公司 | Bacterial marker for assisting COVID-19 diagnosis and application thereof |
| CN111394519B (en) * | 2020-04-13 | 2023-03-21 | 南京实践医学检验有限公司 | Novel coronavirus nucleic acid quantitative detection kit based on digital PCR and application |
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| CN1457777A (en) * | 2003-05-12 | 2003-11-26 | 中国人民解放军军事医学科学院毒物药物研究所 | New use of indole derivatives as anti-SARS medicine |
| CN105758966A (en) * | 2016-03-24 | 2016-07-13 | 中国药科大学 | Metabolic marker group for diagnosing coronary heart disease |
| CN111411104A (en) * | 2020-03-30 | 2020-07-14 | 李长桂 | Magnetic bead for detecting neocoronal pneumonia and preparation method thereof |
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