A lung cancer breath mark detection method coupled with membrane separation and optical cavity ring-down spectroscopy

Abstract

The application provides a lung cancer breath mark detection system coupled with film separation and optical cavity ring-down spectroscopy, and belongs to the technical field of medical treatment; comprising the following steps: S1, preparation of a gas separation film; S2, coupling of the gas separation film with a CRDS system; S3, development of a lung cancer screening breath analysis system based on separation-sensing; the green and efficient film separation method is used to solve the problem of spectral interference that cannot be avoided by the laser-based selectivity in the detection of exhaled gas, a POCT gas sensing system based on separation-sensing and high selectivity and high sensitivity lung cancer screening breath analysis is developed, and a new technology is provided for lung cancer breath screening.

Description

TECHNICAL FIELD

[0001] The present application relates to the medical technical field, and in particular to a lung cancer breath trace detection method coupled with membrane separation and optical cavity ring-down spectroscopy. BACKGROUND

[0002] Lung cancer, also known as primary bronchogenic carcinoma, is the most common lung malignancy originating from the mucosa or glands of the trachea and bronchus. The clinical symptoms of lung cancer are closely related to the tumor size, type, development stage, occurrence site, complications and metastasis, and the common symptoms include cough, blood in sputum, wheezing, chest pain, etc. There may be no obvious symptoms in the early stage of the disease, and some patients are accidentally discovered during physical examination.

[0003] CRDS (optical cavity ring-down spectroscopy, also known as cavity ring-down absorption spectroscopy, and resonant cavity ring-down spectroscopy) is a very sensitive spectroscopy method. It can be used to detect the absolute optical extinction of a sample, including light scattering and absorption. It has been widely used to detect the absorption of gaseous samples at specific wavelengths and can determine the molar fraction of the sample at the level of trillionths.

[0004] In medical treatment of lung cancer patients, in order to more accurately determine the treatment plan, it is usually necessary to detect the lung cancer markers of the patients. The traditional detection method cannot solve the problem of spectral interference that cannot be avoided based on the selectivity of laser in the detection of exhaled gas of patients, thereby affecting the accuracy of detection, affecting the customization of treatment plan in the later stage, and further affecting the treatment and rehabilitation of patients.

[0005] Therefore, the present application provides a lung cancer breath trace detection system coupled with membrane separation and optical cavity ring-down spectroscopy to meet the needs. SUMMARY

[0006] The technical problem to be solved by the present application is to provide a lung cancer breath trace detection system coupled with membrane separation and optical cavity ring-down spectroscopy to solve the problem of existing spectral interference.

[0007] To solve the above technical problems, the present application provides the following technical scheme: a lung cancer breath trace detection method coupled with membrane separation and optical cavity ring-down spectroscopy, comprising the following steps:

[0008] S1: preparation of a gas separation membrane;

[0009] a. confirming the molecular substance with the highest occurrence frequency in the lung cancer markers as the target gas;

[0010] b. performing spectral interference analysis on the molecular substance with the highest frequency to analyze the target gas and define it as the interference gas;

[0011] c. According to the characteristics of the target gas and interfering gas, prepare hollow fiber membranes and modified functional layers that can effectively separate the gas and avoid affecting the spectral detection of the membrane material itself;

[0012] S2: Coupling of the gas separation membrane with the CRDS system;

[0013] a. Test the performance of the CRDS system from multiple angles;

[0014] b. Compare the system with the gold standard GC-MS for trace gas detection using standard gas samples to verify the accuracy of the system;

[0015] c. Use the gas separation membrane and CRDS system to measure the gas concentration changes of single standard gas, mixed gas, and human exhaled gas before and after adding the gas separation membrane, to verify the coupling degree of the gas separation membrane and CRDS system, and to selectively and accurately separate interfering gases at the ultra-trace level (ppbv) without introducing other gas interference.

[0016] S3: Development of a lung cancer screening breath analysis system based on separation-sensing;

[0017] a. A quasi-single-mode high-pulse frequency laser light source;

[0018] b. Two sample chambers treated with silane inert treatment;

[0019] c. A high-reflectivity mirror;

[0020] d. A photodetection module;

[0021] e. A data processing module;

[0022] f. An online measurement sampling device based on a gas separation membrane.

[0023] Preferably, the target gas in step 1 has two types: styrene (C8H8) and ethylbenzene (C8H10), and the interfering gas is acetone.

[0024] Preferably, the characteristics for preparing the hollow fiber membrane and modified functional layer in step 1 are polarity, hydrophilicity and hydrophobicity, and analysis size.

[0025] Preferably, by studying the membrane structure and performance, the thickness and density of the modified functional layer are optimized to achieve precise separation of the target gas and interfering gas in step 1; the gas separation performance of the modified membrane is evaluated using the PTR-MS system, and the preparation process of the separation membrane is further optimized according to the detection characteristics of CRDS to prepare a separation membrane for separating interfering gases at the ultra-trace (ppbv) level.

[0026] Preferably, the direction of measuring the performance of the CRDS system in step 2 is divided into: stability of the operation of the CRDS system, detection limit of the CRDS system, linearity of the CRDS system, repeatability of the CRDS system, response speed of the CRDS system and accuracy of the CRDS system, which are tested from multiple angles to confirm the overall effect of the CRDS system.

[0027] Preferably, the single standard gas detected in step 2 is: target gas and interference gas; and the mixed gas is: a mixture gas of the target gas and the interference gas.

[0028] Preferably, in step 2, the breath is taken as a sample, and the accuracy of the combined system is verified by comparing with the gold standard GC-MS for trace gas detection.

[0029] Preferably, in step 3, the frequency of the quasi-single-mode high-pulse-frequency laser light source needs to be greater than one kilohertz, that is, (>1KHZ); and the reflectivity of the high-reflectivity mirror is >99.985%.

[0030] Compared with the prior art, the present application has at least the following beneficial effects:

[0031] In the above scheme, the green and efficient membrane separation method is used to solve the problem of spectral interference that cannot be avoided in the laser-based selection of exhaled gas detection, and a POCT gas sensing system based on separation-sensing high selectivity and high sensitivity lung cancer screening exhaled gas analysis is developed, which provides a new technology for lung cancer exhaled gas screening.

[0032] The accompanying drawings, which are incorporated herein and constitute part of the specification, illustrate embodiments of the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable a person skilled in the relevant art to implement and use the present disclosure.

[0033] Fig. 1 is a flowchart of the whole process;

[0034] Fig. 2 is a flowchart of step 1;

[0035] Fig. 3 is a flowchart of step 2;

[0036] Fig. 4 is a flowchart of step 3.

[0037] As shown in the drawings, in order to clearly realize the structure of the embodiments of the present application, specific structures and devices are marked in the drawings, but this is only for the need of illustration, and is not intended to limit the present application to the specific structures, devices and environments, and those skilled in the art can adjust or modify these devices and environments according to specific needs, and the adjustments or modifications still include in the scope of the appended claims.

[0038] The following will describe in detail a lung cancer breath trace detection system coupled with membrane separation and optical cavity ring-down spectroscopy according to the present application with reference to the accompanying drawings and specific embodiments. It should be noted that the following embodiments are the best, preferred embodiments, and other alternative ways can also be used by those skilled in the art for implementation of some known technologies; and the accompanying drawings are only used to more specifically describe the embodiments, and are not intended to specifically limit the present application.

[0039] It should be noted that the terms "one embodiment", "an embodiment", "exemplary embodiment", "some embodiments", etc. in the description indicate that the described embodiments can include a specific feature, structure or characteristic, but not necessarily every embodiment includes the specific feature, structure or characteristic. In addition, when a specific feature, structure or characteristic is described in combination with an embodiment, it should be within the knowledge of those skilled in the art to implement such a feature, structure or characteristic in combination with other embodiments, whether or not it is explicitly described.

[0040] Generally, the terms can be understood at least in part from the context in which they are used. For example, depending at least in part on the context, the term "one or more" as used herein can be used to describe any feature, structure, or characteristic in the singular or can be used to describe combinations of features, structures, or characteristics, in the plural. In addition, the term "based on" can be understood as not necessarily requiring a set of exclusive factors, but, alternatively, allowing for existence of additional or even a concurrent factor, depending at least in part on the context in which the phrase is used.

[0041] It can be understood that the meaning of "on", "over", and "above" in the present disclosure should be interpreted in the broadest way, so that "on" not only means "directly on" something, but also includes the meaning of "on" something with intervening features or layers therebetween, and "over" or "above" not only means the meaning of "over" or "above" something, but also can include the meaning of "over" or "above" something without intervening features or layers therebetween.

[0042] In addition, spatially relative terms such as "under", "below", "lower", "over", "upper" and the like can be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. The spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientations depicted in the figures. The device can be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein can be interpreted accordingly.

[0043] In the present embodiment, as Figs. 1 to 4As shown, the embodiment of the present application provides a lung cancer breath trace detection method coupled with membrane separation and optical cavity ring-down spectroscopy, comprising the following steps:

[0044] S1: Preparation of a gas separation membrane;

[0045] a. Confirm the molecular substance with the highest frequency of occurrence in the lung cancer marker, and define it as the target gas;

[0046] b. Perform spectral interference analysis on the molecular substance with the highest frequency, analyze the targeted gas, and define it as the interference gas;

[0047] In the above scheme, the target gas has two types: styrene (C8H8) and ethylbenzene (C8H10), and the interference gas is acetone;

[0048] c. According to the characteristics of the target gas and the interference gas, prepare a hollow fiber membrane and a modified functional layer that can effectively separate the gas and avoid the influence of the membrane material itself on the spectral detection;

[0049] In the above scheme, the characteristics for preparing the hollow fiber membrane and the modified functional layer are polarity, hydrophilicity and hydrophobicity, and analysis size;

[0050] In the above scheme, through the research on the structure and performance of the membrane, the thickness and density of the modified functional layer are optimized to realize the precise separation of the target gas and the interference gas; the gas separation performance of the modified membrane is evaluated by using the PTR-MS system, and the detection characteristics of the CRDS are further optimized to prepare the separation membrane for separating the ultra-trace (ppbv) level interference gas;

[0051] S2: Coupling of the gas separation membrane with the CRDS system;

[0052] a. Test the performance of the CRDS system from multiple angles;

[0053] In the above scheme, the directions for measuring the performance of the CRDS system include the stability of the CRDS system, the detection limit of the CRDS system, the linearity of the CRDS system, the repeatability of the CRDS system, the response speed of the CRDS system, and the accuracy of the CRDS system. By testing from multiple angles, the overall effect of the CRDS system can be confirmed;

[0054] By measuring the CRDS system from multiple angles, the stability, limit, linearity, repeatability, response speed and accuracy of the CRDS system are ensured.

[0055] b. Compare the standard gas sample with the gold standard GC-MS for trace gas detection to verify the accuracy of the system;

[0056] The single standard gas detected in the above scheme is: target gas and interference gas; the mixed gas is: a mixture gas of the target gas and the interference gas;

[0057] c. The gas separation membrane and the CRDS system are combined to detect the gas concentration changes of the single standard gas, the mixed gas and the human exhaled gas before and after adding the gas separation membrane, to verify the coupling degree of the gas separation membrane and the CRDS system, and to selectively and accurately separate the interference gas at the ultra-trace level (ppbv) without introducing other gas interference;

[0058] In the above scheme, the breath is taken as a sample, and compared with the gold standard GC-MS for trace gas detection to verify the accuracy of the combined system;

[0059] S3: Development of a lung cancer screening breath analysis system based on separation-sensing;

[0060] a. A quasi-single-mode high-pulse-frequency laser light source;

[0061] b. Two silanized inert sample chambers;

[0062] c. A high-reflectivity mirror;

[0063] d. A photodetection module;

[0064] e. A data processing module;

[0065] f. An online measurement sampling device based on a gas separation membrane;

[0066] In the above scheme, the frequency of the quasi-single-mode high-pulse-frequency laser light source needs to be greater than one kilohertz, that is, (>1KHZ); the reflectivity of the high-reflectivity mirror is >99.985%, and by limiting the frequency and reflectivity, the system can be operated in a better state, and more accurate detection work can be achieved.

[0067] The present application covers any substitution, modification, equivalent method and scheme made on the essence and scope of the present application. In order to make the public have a thorough understanding of the present application, specific details are described in the following preferred embodiments of the present application, and the present application can also be completely understood without the description of these details for those skilled in the art. In addition, in order to avoid unnecessary confusion to the essence of the present application, well-known methods, processes, procedures, elements and circuits, etc. are not described in detail.

[0068] Those skilled in the art can understand that all or part of the steps in the above-mentioned embodiment methods can be completed by instructing relevant hardware through a program, and the program can be stored in a computer readable storage medium, such as: ROM / RAM, magnetic disc, optical disc, etc.

[0069] The above merely describes the preferred embodiments of the present application, and it should be pointed out that, for those skilled in the art, some improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as falling within the protection scope of the present application.

Claims

1. A method for lung cancer breath trace detection by coupling membrane separation with optical cavity ring-down spectroscopy, characterized in that, It comprises the following steps: S1: preparation of a gas separation membrane; a, confirm the molecular substance with the highest frequency of occurrence in the lung cancer marker, and define it as the target gas; b, analyze the spectrum interference of the molecular substance with the highest frequency, analyze the targeted gas, and define it as the interference gas; c, according to the characteristics of the target gas and the interference gas, prepare a hollow fiber membrane and a modified functional layer that can effectively separate the gas and avoid the influence of the membrane material itself on the spectral detection; S2: coupling of the gas separation membrane and the CRDS system; a, test the performance of the CRDS system from multiple angles; b, compare the standard gas sample with the gold standard GC-MS for trace gas detection to verify the accuracy of the system; c, use the gas separation membrane and the CRDS system to measure the gas concentration changes of single standard gas, mixed gas and human exhaled gas before and after adding the gas separation membrane, and verify the coupling degree of the gas separation membrane and the CRDS system. At the ultra-trace level, the interference gas is selectively and accurately separated without introducing other gas interference; S3: development of lung cancer screening breath analysis system based on separation-sensing; a, quasi-single-mode high pulse frequency laser light source; b, two silanized inert sample chambers; c, high reflectivity mirror; d, photodetection module; e, data processing module; f, online measurement sampling equipment based on gas separation membrane; the frequency of the quasi-single-mode high pulse frequency laser light source in step 3 needs to be greater than one thousand hertz, i.e. >1KHZ; the reflectivity of the high reflectivity mirror is >99.985%. The target gas in step 1 has two kinds, which are styrene (C8H8) and ethylbenzene (C8H10), and the interference gas is acetone.

2. The method according to claim 1, wherein, The characteristics for preparing the hollow fiber membrane and the modified functional layer in step 1 are polarity, hydrophilicity and hydrophobicity, and analysis size.

3. The method according to claim 1, wherein, In step 1, by studying the structure and performance of the membrane, the thickness and density of the modified functional layer are optimized to achieve precise separation of the target gas and the interference gas; the gas separation performance of the modified membrane is evaluated by PTR-MS system, and the preparation process of the separation membrane is further optimized according to the detection characteristics of CRDS to prepare a separation membrane for separating interference gas at the ultra-trace level.

4. The method according to claim 1, wherein, In step 2, the directions for measuring the performance of the CRDS system include the stability of the CRDS system, the detection limit of the CRDS system, the linearity of the CRDS system, the repeatability of the CRDS system, the response speed of the CRDS system and the accuracy of the CRDS system. From multiple angles, the overall effect of the CRDS system can be confirmed.

5. The method according to claim 1, wherein, The single standard gas detected in step 2 is the target gas and the interference gas; the mixed gas is the mixture gas of the target gas and the interference gas.

6. The method according to claim 1, wherein, In step 2, the breath is taken as a sample, compared with the gold standard GC-MS for trace gas detection, and the accuracy of the combined system is verified.

7. The method according to claim 1, wherein, ​

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