Detection system for screening diseases through exhalation of VOC (Volatile Organic Compounds) marker

Abstract

The utility model relates to a detection system for screening diseases through exhalation of a VOC (volatile organic compound) marker. The detection system comprises a sensing chip, a sample collecting device and a Raman spectrometer, wherein the sample collecting device is used for enabling a detection sample to act on the sensing chip, and the Raman spectrometer is used for detecting the sensing chip. According to the detection system for screening the diseases through the exhalation of the VOC marker, accurate, rapid and non-invasive screening of the diseases can be realized through the detection of the Raman spectrometer.

Description

Technical Field

[0001] This utility model relates to disease screening, and more particularly to a detection system suitable for screening diseases such as expiratory cancer and bronchiectasis. Background Technology

[0002] Cancer is one of the greatest threats to human life and health. Because cancer often presents with no obvious symptoms during its latent period, and because commonly used diagnostic methods such as imaging, pathology, and microscopy are invasive, expensive, and time-consuming, most diagnosed patients are currently in the middle or late stages and have short survival times. However, if cancer is detected in its early stages or even during its latent period, patients may be able to reverse or prevent the development of cancer by consciously improving their lifestyle, diet, and exercise habits to enhance their anti-cancer immunity.

[0003] When cancer develops in the human body, tumor cells produce certain special chemical components. These marker substances are released into the bloodstream, exchanged through the lungs, and reflected as measurably highly expressed components in exhaled breath. Based on this, by detecting the composition and content of volatile substances in the exhaled breath of cancer patients and healthy individuals that show significant differences, the metabolic status of cancer cells and the stage of the disease can be determined. Therefore, developing a non-invasive, rapid, accurate, and low-cost cancer screening system can fill the gap in early cancer screening and diagnosis. Utility Model Content

[0004] To overcome at least one of the defects of the prior art, in a first aspect, an embodiment of the present invention provides a detection system for screening diseases through breath using VOC markers, comprising a sensor chip, a sample collection device, and a Raman spectrometer; the sample collection device is used to apply a test sample to the sensor chip, and the Raman spectrometer is used to detect the sensor chip; the test sample is the gas exhaled by the test subject, and the sample collection device includes a gas collection component and a collection chamber, the gas collection component being used to hold the gas; the gas can act on the sensor chip within the collection chamber.

[0005] According to one embodiment of the present invention, a one-way valve and an air blowing nozzle are provided on the gas collecting component.

[0006] According to one embodiment of the present invention, the sample collection device further includes a power component, and a closed fluid passage is formed between the power component and the collection chamber. Under the action of the power component, the gas can circulate within the fluid passage.

[0007] According to one embodiment of the present invention, the power component is an air pump.

[0008] According to one embodiment of the present invention, a flow meter is provided on the fluid passage.

[0009] According to one embodiment of the present invention, the collecting chamber is tubular and includes an air inlet and an air outlet, wherein the air inlet is connected to the air collecting component.

[0010] According to one embodiment of the present invention, the air inlet is connected to the air collecting component and the flow meter respectively, and the air outlet is connected to the power component.

[0011] According to one embodiment of the present invention, the Raman spectrometer is a surface-enhanced Raman spectrometer.

[0012] According to one embodiment of the present invention, the sensing chip includes a metal-organic framework film layer.

[0013] According to one embodiment of the present invention, the metal-organic framework is MIL-100(Fe) or MIL-125(Ti).

[0014] This invention discloses a detection system for screening diseases through breath using VOC biomarkers. By using a Raman spectrometer to detect the sensor chip, it can achieve accurate, rapid, and non-invasive disease screening.

[0015] In this invention, the above-described technical solutions can be combined with each other to achieve more preferred combinations. Other features and advantages of this invention will be set forth in the following description, and some advantages will become apparent from the description or be learned by practicing the invention. The objectives and other advantages of this invention can be realized and obtained from the description and accompanying drawings, which are particularly pointed out. Attached Figure Description

[0016] The accompanying drawings are for illustrative purposes only and are not intended to limit the scope of this invention. Wherein:

[0017] Figure 1 This is a schematic diagram of a vertical cross-section of a collection cavity with a metal-organic framework membrane layer according to one embodiment of the present invention.

[0018] Figure 2 This is a top view of a sample collection device according to one embodiment of the present invention;

[0019] Figure 3 This is a flowchart illustrating a cancer screening method according to one embodiment of the present invention.

[0020] Figure 4 This is the Raman detection spectrum of Embodiment 1 of this utility model;

[0021] Figure 5 This is the Raman detection spectrum of Embodiment 2 of this utility model.

[0022] The annotations in the attached figures are explained as follows:

[0023] 10. Collection chamber; 11. Air inlet; 12. Air outlet; 20. Metal-organic framework membrane layer; 30. Gas collection component; 31. One-way valve; 32. Air nozzle; 40. Power component; 50. Flow meter. Detailed Implementation

[0024] The preferred embodiments of this utility model are described in detail below. The accompanying drawings constitute a part of this utility model and, together with the embodiments, are used to illustrate the principles of this utility model, but are not intended to limit the scope of this utility model. The vertical cross-section of the collecting cavity refers to the cross-section along the direction parallel to the axis of the collecting cavity.

[0025] One embodiment of this utility model provides a detection system for screening diseases through breath using VOC (volatile organic compound) markers, including a sensor chip, a sample collection device, and a Raman spectrometer; wherein, the detection sample is the gas exhaled by the tester, the sample collection device is used to apply the detection sample to the sensor chip, and the Raman spectrometer is used to detect the detection sample on the sensor chip.

[0026] In one embodiment, the sensing chip includes a metal-organic framework film layer formed of a metal-organic framework.

[0027] The detection system of this invention can be used for breath screening of diseases, and the screening has good accuracy. Therefore, it can be widely used for non-invasive screening, diagnosis and postoperative monitoring of diseases.

[0028] In one embodiment, metal-organic frameworks (MOFs) can be combined with VOC biomarkers. The MOFs are detected using Raman spectroscopy, and the comparison of the detection results can determine whether the test subject has a disease. Furthermore, the fingerprint spectrum, shift map, and ion concentration map of the Raman spectrum can be used for further analysis, enabling precise identification and content analysis of VOC biomarkers. Moreover, the measured Raman shift map can display the peak values ​​of different substances; comparing this with the peak values ​​of healthy individuals and patients at different stages allows for further analysis and judgment.

[0029] The detection system of this invention, by combining a metal-organic framework with VOC markers, leverages the advantages of kinetic equilibrium. Specifically, using only a single gas sample bag, measurements at different time points can achieve the same results (e.g., day 1 and day 10). In contrast, mass spectrometry and chromatography require the adsorption of all gases at once, necessitating a second gas bag from the same person for subsequent measurements. Due to minor leaks in the sealed container, this can lead to discrepancies between the two results (e.g., day 1 and day 10).

[0030] In one embodiment, reference is made to Figure 1 , 2 As shown, the metal-organic framework membrane 20 is disposed in the collection chamber 10; furthermore, a solution of the metal-organic framework can be disposed on the inner wall of the collection chamber 10 to form a liquid film, which is then dried to form the metal-organic framework membrane 20.

[0031] In one embodiment, the collection chamber 10 may be transparent and its material may not contain volatile substances. For example, the material of the collection chamber 10 may be one or more of quartz, glass, and PVDF. Furthermore, the collection chamber 10 may be a tubular structure.

[0032] In one embodiment, the metal-organic framework can be prepared as a solution, and the solution can be applied to the inner wall of the collection chamber 10 through a capillary tube, so that the metal-organic framework is adsorbed on the inner wall. After drying, a metal-organic framework film layer 20 is formed. Then, the collection chamber 10 can be sealed and stored in the dark.

[0033] In one embodiment, the metal-organic framework disposed in the collection chamber 10 can be a thin film or membrane layer, or multiple thin films or membrane layers, and multiple metal-organic framework membrane layers can be arranged in an array in the collection chamber 10.

[0034] In one embodiment, the metal-organic framework disposed in the collection chamber 10 may be of one type, and one type of metal-organic framework may be combined with one or more VOC markers; or there may be multiple types of metal-organic frameworks, and multiple types of metal-organic frameworks may be combined with one or more VOC markers.

[0035] In one embodiment, the metal-organic framework is an existing material.

[0036] In one embodiment, the metal-organic framework includes an organic ligand and a metal ion. The organic ligand may include one or more of pyromellitic acid, terephthalic acid, and imidazole, and the metal ion may include one or more of iron, zirconium, chromium, titanium, and zinc ions. The metal-organic framework may be MIL-100 (Fe) or MIL-125 (Ti).

[0037] In one embodiment, the types of ligand functional groups and metal ions in the metal-organic framework can be adjusted to enable them to bind with the analyte (e.g., a VOC marker), thereby enriching the analyte on the metal-organic framework. The adjustment methods used may include, for example, diffusion, volatilization, ultrasonic synthesis, solid-phase reaction, ionic liquid, sublimation, microwave, and two-phase synthesis.

[0038] In one embodiment, the diseases screened may be cancer, bronchiectasis, asthma, hepatitis, enteritis, diabetes, Alzheimer's disease, etc.; cancer may be, for example, lung cancer, stomach cancer, or esophageal cancer.

[0039] In one embodiment, the analyte that can bind to the metal-organic framework membrane layer 20 can be a tumor marker, such as a lung cancer marker. The lung cancer marker can be one or more of isopropanol, acetaldehyde, benzene, toluene, isoprene, formaldehyde, 4-ethylbenzaldehyde, acetone, and 8-ethylpentadecane.

[0040] In one embodiment, the markers used to detect bronchiectasis can be sulfides, unsaturated hydrocarbons, or aromatic compounds, such as toluene or isoprene.

[0041] In one embodiment, the Raman spectrometer used may be a surface-enhanced Raman spectrometer.

[0042] In one embodiment, reference is made to Figure 2 As shown, the sample collection device includes:

[0043] Gas collection component 30, used to collect the gas exhaled by the tester; and

[0044] The sensing chip can be placed in the collection chamber 10 during the sample collection process;

[0045] During operation, VOC markers in the gas can act on the metal-organic framework film layer 20 of the sensor chip within the collection chamber 10, and be detected by a Raman spectrometer.

[0046] In one embodiment, the gas collection component 30 can be a gas collection bag, on which a one-way valve 31 and a mouthpiece 32 can be provided. The patient can blow exhaled gas into the gas collection bag through the mouthpiece 32 to achieve gas collection.

[0047] In one embodiment, the sample collection device further includes a power component 40, and a closed (or annular) fluid passage is formed between the power component 40 and the collection chamber 10. Under the action of the power component 40, the gas can circulate within the fluid passage to fully contact the metal-organic framework of the sensor chip, thereby enriching as many VOC markers of the analyte as possible on the metal-organic framework to further improve the accuracy of detection.

[0048] In one embodiment, the gas collection component 30 can be connected to the fluid passage, and the gas collection component is compressed to increase the gas density therein; the gas in the gas collection component 30 flows into the fluid passage, and under the action of the power component 40, the gas circulates in the fluid passage and comes into contact with the sensor chip multiple times, and the VOC markers therein react with the metal-organic framework film layer 20 of the sensor chip, thereby accumulating on the sensor chip.

[0049] In one embodiment, a flow meter 50 is provided in the fluid passage to control the gas flow rate and adjust the gas velocity in the fluid passage. The collecting chamber 10, the flow meter 50, and the power unit 40 are interconnected to form the fluid passage. Further, the power unit 40 can be a vacuum pump, and the collecting chamber 10 can be a long tubular structure including an inlet 11 and an outlet 12. The inlet 11 can be connected to the gas collecting component 30 and the flow meter 50 respectively, and the outlet 12 is connected to the power unit 40. During operation, the gas is slowly drawn into the fluid passage by the power unit 40 (e.g., a vacuum pump) to form a stable airflow. The speed of the vacuuming can be adjusted in conjunction with the reading of the flow meter 50 to ensure that the gas reacts fully with the metal-organic framework; the amount of gas drawn can be no more than 0.8L.

[0050] In one embodiment, the circulation time of the gas in the fluid passage can be 2 to 30 minutes, for example, 5 minutes, 10 minutes, 15 minutes, 20 minutes, or 25 minutes.

[0051] In one embodiment, the disease screening is a breath screening; further, the patient's exhaled gas may be brought into contact with the metal-organic framework membrane 20, so that the VOC markers that may be contained therein act on the metal-organic framework membrane 20, and then detected by Raman spectroscopy.

[0052] The disease screening process according to one embodiment of this utility model includes the following steps:

[0053] Fabrication of sensor chips;

[0054] Gas collection;

[0055] The gas is brought into contact with the sensing chip, causing the VOC markers within it to act on the sensing chip; and

[0056] The obtained sensor chip is tested using a Raman spectrometer, and the screening results are obtained by comparing the data.

[0057] In one embodiment, a working curve for VOC markers can be created using detection data from a Raman spectrometer. The specific content of the VOC markers can then be determined by calculating the equation of the fitted curve. For example, the fitted equation could be Y = aX + b, where Y is the Raman peak intensity and X is the concentration. The concentration X can be calculated by substituting the measured Y value into the equation.

[0058] The detection system of this invention features rapid detection, completing the detection within approximately 3 to 20 minutes, while existing mass spectrometry detection requires tens of minutes to obtain a spectrum. Furthermore, the spectral range of the detection system of this invention is 200–3000 cm⁻¹. -1 It has fewer interference peaks.

[0059] The detection system of this invention employs a metal-organic framework (MOF) membrane as the sensing chip for disease detection. Through the adjustable design characteristics of the MOF to enrich specific analytes (e.g., VOC biomarkers), it can screen and enrich specific analytes from complex gas backgrounds, solving the problem of excessive complex interference in exhaled breath and effectively improving detection speed and accuracy. Furthermore, based on the Raman enhancement effect, Raman spectroscopy is used for the detection and identification of VOC biomarkers. By judging parameters such as Raman spectral fingerprints, shift maps, and ion concentration maps, accurate identification and content analysis of VOC biomarkers are achieved. Compared to the currently used gas chromatograph or mass spectrometer analysis methods, this reduces cumbersome pre-analytical preparation work and avoids the need to analyze all substances, significantly reducing the workload and analysis time. In addition, the detection system of this invention can not only identify the presence or absence of target biomarkers but also perform quantitative analysis. Unlike the semi-quantitative analysis of mass spectrometry, the detection results can serve as a basis for judging the early, middle, and late stages of cancer.

[0060] This invention discloses a detection system for screening diseases using VOC biomarkers in exhaled breath. It fully considers the influencing factors of clinical exhaled breath samples, further improves the collection method for specific VOC biomarker samples, enhances the targeting of the detection, and simultaneously improves detection speed and accuracy. Accuracy refers to the fact that the gas sample is relatively stable, and the results obtained from testing at any time within several days are essentially consistent.

[0061] The following description, in conjunction with the accompanying drawings and specific embodiments, further illustrates an embodiment of the present invention: a detection system for screening diseases through breath using VOC markers and its use.

[0062] Example 1

[0063] Fabrication of sensor chips

[0064] 1) Prepare a saturated solution of the purchased metal-organic framework MIL-100(Fe).

[0065] 2) At room temperature, 10 micrograms of the above-mentioned metal-organic framework MIL-100 (Fe) saturated solution are dipped into the capillary tube and dotted into the collection chamber 10 at 15 mm intervals. Six liquid films are formed in the collection chamber 10 and adsorbed in the collection chamber 10. Nitrogen gas is blown to dry the film to obtain the metal-organic framework film layer 20 (sensor chip). After sealing the collection chamber 10, it is stored in the dark.

[0066] Gas collection

[0067] The participants in the gas sampling experiment included 3 healthy individuals and 3 lung cancer patients. Participants were prohibited from staying up late for 48 hours prior to gas sampling, from strenuous exercise for 8 hours prior, from eating spicy or irritating foods for 12 hours prior, from smoking, and from drinking any beverages or alcoholic drinks. Gas sampling was conducted on an empty stomach for 6 hours. Taking medication could affect the results, and gas sampling was not conducted after taking any medication.

[0068] Before collecting gas, the test personnel took a deep breath and exhaled the gas from their lungs into the 1L gas collection bag through the mouthpiece until the gas collection bag was full of gas.

[0069] Collection of test samples

[0070] The aforementioned collection chamber 10, flow meter, and vacuum pump are interconnected to form a fluid passage. The collection chamber 10 is a transparent quartz tube, including an inlet and an outlet. The inlet is connected to the flow meter, and the outlet is connected to the vacuum pump. The aforementioned gas collection bag is connected to the collection chamber 10 through the inlet 11. The vacuum pump is turned on, and gas is slowly drawn in to allow the gas in the gas collection bag to enter the fluid passage and circulate within it, allowing the VOC marker in the gas to fully react with the metal-organic framework membrane layer 20. The gas flow time is 10 minutes. Afterward, the vacuum pump is stopped, and the collection chamber 10 containing the sensor chip is removed, sealed at both ends, and placed in a Raman spectrometer for detection.

[0071] The VOC markers detected included toluene, acetone, isopropanol, isoprene, formaldehyde, and 4-ethylbenzaldehyde.

[0072] Processing of test results

[0073] See the measured Raman spectrum. Figure 4 ,according to Figure 4 It can be seen that at 980cm -1 At this point, the peak intensity and the proportion of the peak to the right side differ between the spectra of lung cancer patients and healthy individuals; at 746 cm⁻¹ -1 At this point, compared to the atlas of healthy individuals, the atlas of lung cancer patients shows a distinct signal peak. Here, a signal peak refers to the appearance of a new peak, the disappearance of an old peak, or a change in the peak intensity ratio.

[0074] Example 2

[0075] This example uses essentially the same raw materials and methods as Example 1 to prepare the sensor chip and perform related Raman tests. The only difference is that the metal-organic framework used is MIL-125(Ti), and the subjects tested are bronchiectasis patients and healthy individuals. The biomarkers detected are toluene and isoprene. The obtained spectra can be found in [reference needed]. Figure 5 .exist Figure 5 In the diagram, bronchiectasis 1, bronchiectasis 2, bronchiectasis 3, bronchiectasis 4, and bronchiectasis 5 represent the atlas of patients with bronchiectasis, while HC1 represents the atlas of healthy individuals. Among these, 1020cm... -1 and 800cm -1 The peaks at the left and right wavenumbers are characteristic peaks of toluene; 500 cm⁻¹ -1 and 1310cm -1 The peaks at the left and right wavenumbers are isoprene. After isoprene interacts with the metal-organic framework, charge transfer occurs, causing the peak at this point to weaken or disappear.

[0076] The above description is only a preferred embodiment of the present utility model, but the protection scope of the present utility model is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present utility model should be included within the protection scope of the present utility model.

Claims

1. A detection system for screening diseases through breath using VOC biomarkers, characterized in that, include: Sensor chip; A sample collection device for applying a test sample to the sensor chip; as well as A Raman spectrometer is used to detect the sensor chip; The test sample is the gas exhaled by the tester. The sample collection device includes a gas collection component and a collection chamber. The gas collection component is used to hold the gas. The gas can act on the sensor chip within the collection chamber. The sample collection device also includes a power component, and a closed fluid passage is formed between the power component and the collection chamber. Under the action of the power component, the gas can circulate within the fluid passage, so that the VOC marker of the analyte is enriched on the metal-organic framework. The Raman spectrometer is a surface-enhanced Raman spectrometer; The sensing chip includes a metal-organic framework film layer, which includes organic ligands and metal ions. The organic ligands may include one or more of pyromellitic acid, terephthalic acid, and imidazole, and the metal ions may include one or more of iron ions, zirconium ions, chromium ions, titanium ions, and zinc ions. The diseases to be screened include bronchiectasis, asthma, hepatitis, enteritis, diabetes, and Alzheimer's disease.

2. The detection system according to claim 1, characterized in that, A one-way valve and an air blowing nozzle are provided on the gas collecting component.

3. The detection system according to claim 1, characterized in that, The power component is an air pump.

4. The detection system according to claim 1, characterized in that, A flow meter is installed in the fluid passage.

5. The detection system according to claim 4, characterized in that, The collecting chamber is tubular and includes an air inlet and an air outlet, with the air inlet connected to the air collecting component.

6. The detection system according to claim 5, characterized in that, The air inlet is connected to the air collecting component and the flow meter, respectively, and the air outlet is connected to the power component.

7. The detection system according to claim 1, characterized in that, The metal-organic framework is MIL-100(Fe) or MIL-125(Ti).

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