CN2778198Y - Respiration checkout gear for early lung carcinoma diagnosis - Google Patents

Abstract

The utility model discloses a breathing detection device for diagnosing early lung cancer. It includes a solid phase microextraction head (1), a gas thermal desorber (2), a signal processor (6), and a computer (7); it is characterized in that: the solid phase microextraction head (1) is inserted into the gas thermal desorber ( 2), the outlet of the gas thermal desorber (2) is connected to the inlet of the capillary separation column (3) installed in the temperature control box, and the outlet of the capillary separation column (3) reaches the detection head (5) through the detection head interface (4) The difference frequency signal generated by the organic gas sensitive film is transmitted to the signal processor (6) and then connected to the computer (7). First, the suspected lung cancer is adsorbed by the organic gas sensitive film on the detection head, so as to detect the content of the measured organic gas components, and perform data image processing and neural network pattern recognition on the detected 11 kinds of lung cancer symbolic organic components, so as to be able to diagnosed with lung cancer. The utility model can also perform qualitative and quantitative detection of volatile organic compounds in the fields of food, chemical industry, biomedicine, agricultural product processing, traditional Chinese medicine, air pollution monitoring and the like.

Description

Breath detection device for diagnosing early lung cancer

technical field

The utility model relates to a breathing detection device for diagnosing early lung cancer.

Background technique

It is estimated that there are about 600,000 new lung cancer patients every year in the world. Lung cancer is currently one of the most common malignant tumors in the world, and the incidence rate has a tendency to increase significantly in most countries. The five-year survival rate of lung cancer is 14%. If it can be diagnosed and treated at an early stage, the five-year survival rate is 48%. Therefore, it is of great practical significance to design a breath detection instrument that can non-invasively detect early lung cancer patients. . At present, clinically, common diagnostic methods for lung cancer include: X-ray examination, computerized tomography (CT), magnetic resonance tomography (MRI), sputum exfoliated cell examination, fiberoptic bronchoscopy, percutaneous lung biopsy, etc. The equipment of these methods is huge and expensive, the trauma to the patient is great, skilled operators are required, and most importantly, early diagnosis cannot be carried out.

Contents of the invention

The purpose of the utility model is to provide a breath detection device for diagnosing early lung cancer, which can perform qualitative and quantitative detection of volatile organic gases (VOC) in the breath of suspected early lung cancer patients.

In order to achieve the above object, the technical scheme that the utility model adopts is as follows:

1. Breath detection method for early diagnosis of lung cancer:

First, the respiratory gas of suspected lung cancer patients is pre-enriched with a solid-phase microextraction head, and then the solid-phase microextraction needle adsorbed with organic gas components is inserted into the gas thermal desorber to make it thermally desorbed. The organic gas components are separated through the gas chromatography capillary separation column, so that the measured organic gases arrive at the detector made of a pair of high-frequency delay line surface acoustic wave sensors in sequence, and are adsorbed by the organic gas sensitive film on the detector. In this way, the measured organic gas components are detected, and data image processing and neural network pattern recognition are performed on the detected 11 kinds of lung cancer symbolic organic components, so that lung cancer patients can be diagnosed.

2. A breathing detection device for diagnosing early lung cancer, including a solid-phase micro-extraction head, a gas thermal desorber, a signal processor, and a computer. The solid-phase microextraction head is inserted into the gas thermal desorber, the outlet of the gas thermal desorber is connected to the inlet of the capillary separation column installed in the temperature control box, and the outlet of the capillary separation column reaches the organic gas sensitive membrane of the detection head through the detection head interface. The generated difference frequency signal is sent to the signal processor and then connected to the computer.

The detection head includes: two groups of interdigitated electrode channels are made of aluminum film on a substrate made of 128° Y-cut X-propagated LiNbO ₃ , two 2.5mm delay lines are made of aluminum film in the middle, and a A layer of 100nm polyisobutylene organic gas sensitive film is coated on the delay line as the detection channel, and the other uncoated film is used as the reference channel. The signals generated by the two channels are connected to the mixer through the RF amplifier to generate a difference frequency signal for detection , input the difference frequency signal to the signal processor.

The detection head interface includes: the capillary outlet nozzle is fixed on the heater, the capillary separation column is connected to the organic gas sensitive film on the detection head through the nozzle, and a cylindrical heat-conducting metal sleeve made of aluminum alloy is placed on the outside of the nozzle , the bottom of which is fixed on the heater, and a heat-insulating cap is made of heat-insulating material on the upper part of the heat-conducting metal sleeve, and the detection head is buckled on the cap to form a non-airtight air chamber. The detection head and 3cm×3cm The semiconductor refrigerating sheet is fixed together, so that the cold surface of the semiconductor refrigerating sheet is connected with the bottom of the detection head through thermal silica gel, and the hot surface of the semiconductor refrigerating sheet is connected with the heat sink through thermally conductive silica gel.

The utility model has the advantages that the detection device is small, the detection range is wide, the detection sensitivity is high, the detection is fast, the use is convenient, and the lung cancer suspected crowd can be detected early and non-invasively. Since the new breathing detection instrument can detect organic components in gases, it can also perform qualitative and quantitative detection of volatile organic compounds in the fields of food, chemical industry, biomedicine, agricultural product processing, traditional Chinese medicine, and air pollution monitoring.

Description of drawings

Below in conjunction with accompanying drawing and embodiment the utility model is further described.

Fig. 1 is the basic structural schematic diagram of the utility model;

Fig. 2 is a schematic diagram of the basic structure of the detection head of the present utility model;

Fig. 3 is a schematic diagram of the basic structure of the detection head interface of the present invention;

Fig. 4 is the schematic diagram of the thin film preparation process by spin-dispensing technology;

Fig. 5 is a schematic diagram of the image processing process of the present utility model;

Fig. 6 is the baseline response of the present utility model;

Fig. 7 is the response curve of the utility model to the respiratory gas of a lung cancer patient;

Fig. 8 is the response characteristic curve of the utility model to different concentrations of decane gas.

In the figure: 1. Solid-phase microextraction head, 2. Gas thermal desorber, 3. Capillary separation column installed in a temperature control box, 4. Detection head interface, 5. Detection head, 6. Signal processor, 7 , computer, 8, substrate made of LiNbO ₃ with 128°Y cut X propagation, 9, radio frequency amplifier, 10, detection channel, 11, reference channel, 12, organic gas sensitive film, 13, mixer, 14, Capillary outlet nozzle, 15, heater, 16, cylindrical heat-conducting metal sleeve, 17, thermal insulation cap, 18, heat-conducting silica gel, 19, heat sink, 20, semiconductor refrigeration sheet.

Detailed ways

1, the concrete structure of the present utility model:

As shown in Figure 1, a kind of equipment that is used for the breathing detection method of diagnosis early stage lung cancer, comprises solid phase microextraction head 1, gas thermal desorber 2, signal processor 6 (frequency device 1k～1MHz), computer 7 ( PC). The solid-phase microextraction head 1 is inserted into the gas thermal desorber 2, the outlet of the gas thermal desorber 2 is connected to the inlet of the capillary separation column 3 installed in the temperature control box, and the outlet of the capillary separation column 3 installed in the temperature control box passes through The detection head interface 4 reaches the organic gas sensitive film of the detection head 5, and the generated difference frequency signal is sent to the signal processor 6 and then connected to the computer 7.

As shown in Figure 2, the detection head 5 includes: on the substrate 8 made of LiNbO ₃ with 128° Y-cut X-propagation, two groups of interdigitated electrode channels are made of aluminum film, and aluminum film is used between them. Two 2.5mm delay lines, one layer of 100nm polyisobutylene organic film 12 is coated on one delay line as the detection channel 10, and the other is not coated as the reference channel 11, and the signals generated by the two channels pass through the radio frequency amplifier 9 (model MAX2650) is connected to the mixer 13 (model MC1496) to generate a beat frequency signal for detection, and input the beat frequency signal to the signal processor 6.

As shown in Figure 3, the detection head interface 4 includes: the capillary outlet nozzle 14 is fixed on the heater 15, and the capillary separation column 3 installed in the temperature control box is connected to the organic gas sensitive membrane on the detection head 5 through the nozzle 12. Put a cylindrical heat-conducting metal sleeve 16 made of aluminum alloy on the outside of the spray head, the bottom of which is fixed on the heater 15, and a heat-insulating cap 17 is made of heat-insulating material on the upper part of the heat-conducting metal sleeve 16. Buckle the detection head 5 on the cap to form a non-airtight air chamber, fix the detection head 5 and the 3cm×3cm semiconductor cooling chip 20 together, and make the cold surface of the semiconductor cooling chip 20 and the bottom of the detection head 5 conduct heat The silica gel 18 is connected, and at the same time, the hot surface of the semiconductor refrigeration sheet 20 is connected to the heat sink 19 through the thermally conductive silica gel 18 .

When the respiratory gas of suspected lung cancer patients is pre-enriched by the solid-phase microextraction head, it is adsorbed on the solid-phase microextraction head, desorbed in the gas thermal desorber, and sent to the capillary separation column with nitrogen as the carrier gas. separate. The separated organic gas components arrive at the detection head through the detection head interface in turn, and are adsorbed by the organic gas sensitive film on the detection head. The detection head generates a frequency change signal, which is mixed with the reference channel to obtain a difference frequency signal. The difference frequency signal After being accepted and processed by the signal processor, it is sent to the computer for final image processing and neural network analysis.

2, the preparation method of the utility model:

(1) Design and manufacture of delay line surface acoustic sensor

A 128° Y-cut X-propagation LiNbO ₃ single chip is selected as the piezoelectric substrate of the acoustic surface sensor, that is, the substrate 8 . After polishing and cleaning, use the etching technology that has been widely used in the field of semiconductor integrated circuits to make 500nm thick, 12.82um wide interdigitated electrode (IDT) and a square delay line with a side length of 2.5mm with aluminum film.

The design parameters are as follows:

(1) 128°Y-cut X-propagated LiNbO ₃ substrate

(2) IDT refers to the width, and the finger spacing is 12.82um

(3) Aperture w=2.5mm

(4) The output logarithm is N1=46 pairs of fingers

(5) The input logarithm is N2=29 pairs of fingers

(6) Bandwidth: From Δf=f ₀ /N; f ₀ =78.1MHz, N=46, it can be seen that the bandwidth Δf=1.70MHz

(2) Preparation of organic gas sensitive film 12 sensor:

Select chloroform and toluene as organic solvent, mass ratio 1: 1, after fully mixing, add polyisobutylene (PIB) as solute, at room temperature, under one atmospheric pressure, make the solution that mass percent is 15%～20%, take 0.4 μL of this solution is drip-coated on the surface of the SAW sensor at a rotation speed of 1500 to 2000 revolutions per minute, and the coating film ends after 60 seconds of rotation, as shown in Figure 4. While coating the film, there should be saturated water vapor in the space of the coating film, because the film produced in this way has porous characteristics, which can improve the adsorption capacity of the film to VOC gas molecules. Put the film-coated sensor in a vacuum vessel to dry, and put the vessel in an oven to keep a constant temperature of 45°C for at least 2 or 3 days to remove the solvent in the film. This completes the preparation of the thin film sensor.

(3) Production of the detection head 5:

Using the aforementioned thin-film sensor as the detection channel 10 and an uncoated sensor as the reference channel 11, a positive feedback circuit is used to make it oscillate and generate a frequency signal. After passing through the mixer circuit and the low-pass circuit, a difference frequency signal is generated. A refrigerator made of peltiers 20 cools the bases of the two sensors so as to keep the sensors working at room temperature. In this way, the production of the detection head is completed, and we can determine the content of the detected volatile organic compounds by detecting the change of the difference frequency signal.

(4) Image processing method of detection data:

Figure 5 shows an image recognition method used to diagnose lung cancer patients. The ideal respiratory response of a lung cancer patient can be determined from the standard sample results (Table 1), as shown in Figure 5(a). The ideal response of this virtual sensor array is transformed into a polar coordinate representation, and then the polar coordinate response of the lung cancer patient is superimposed on it, as shown in Fig. 5(b). Finally, the overlapping area of each VOC response was calculated.

(5) Design of neural network:

Each VOC component corresponds to a parameter, the overlapping area. It includes two information quantities: frequency response (Hz) and retention time (mim), frequency response refers to the concentration of VOC and retention time refers to the type of the VOC component. Because 11 kinds of characteristic VOC components are calibrated, there are 11 input data from the SAW sensor, and there are 3 output results, lung cancer patients, healthy people and suspected patients. The artificial neural network uses BP-ANN.

During neural network training, three states are defined: first, if the breathing gas does not contain these 11 kinds of lung cancer characteristic VOC gases, it is a healthy person; second, if the breathing gas only contains these 11 kinds of lung cancer characteristic VOC gases. One of them is a suspected patient; third, if the respiratory gas contains more than two types of these 11 kinds of VOC gases characteristic of lung cancer, it is a lung cancer patient. Table 111 VOCs as characteristic gases of lung cancer, arranged in order of occurrence frequency in lung cancer respiratory gases from large to small VOC name Average retention time ±0.020(min) Styrene 5.140 Decane 8.598 Isoprene 1.390 benzene 1.940 Undecane 11.598 Hexene 1.623 Hexanal 3.323 Propylbenzene 6.807 1,2,4 Trimethylbenzene 7.890 Heptanal 5.332 methyl-cyclopentane 1.807

The principle of detection equipment

The delay line surface acoustic wave sensor has a mass deposition effect. When a substance is deposited on the delay line, it will change the propagation speed of the sound wave, thereby changing the oscillation frequency of the sensor. When the organic film on the surface of the sensor absorbs volatile organic compounds in the gas, The sensor frequency has changed. By detecting the frequency change of the sensor, the content of volatile organic compounds can be converted.

The capillary column of gas chromatography has ideal time separation characteristics. The retention time of the sensor response is related to the time for each chemical component to pass through the capillary column. Since different chemical components move at different rates in the coating film inside the capillary column, the capillary column can Separate the chemical components in the gas sample at the injection port into individual components. By calculating the retention time of each response, each VOC can be detected. In this way, the qualitative and quantitative detection of volatile organic compounds is completed.

Characteristics of the instrument

(1) Stability

The baseline of the instrument over a period of 25 minutes is shown in Figure 6, sampled at 13 points per second. The fluctuation is within 100Hz, usually our detection time is 13 minutes. This result shows that the instrument has high stability.

(2) Detection sensitivity

Figure 7 shows the spectral response of the instrument when detecting the breath gas of a lung cancer patient. Its sensitivity to styrene response is 3.24ng/Hz.

(3) The characteristic curve and characteristic parameters of the testing instrument

The standard response curve of the detection instrument to decane is shown in Figure 8. There are different detection limits for each volatile organic compound, and the best detection limit is 1×10 ^-8 mol/L of p-styrene. The response time of the sensor is less than 3 seconds (the response time refers to the time taken to reach the peak value), and it is relatively slow when the concentration is high. And when the low concentration was measured after the high concentration VOC was measured, no obvious concentration hysteresis effect was found. The film sensor can be used repeatedly for a long time, and has good repeatability, which is also a characteristic of the sensor.

Claims (3)

1, a kind of device for detecting respiratory that is used to diagnose the early stage of lung cancer comprises solid phase micro-extracting head (1), gas thermal desorption device (2), signal processor (6), computer (7); It is characterized in that: solid phase micro-extracting head (1) inserts gas thermal desorption device (2), the inlet of the capillary separation column (3) of gas thermal desorption device (2) outlet tipping in temperature-controlled cabinet, the outlet of capillary separation column (3) connects computer (7) through the organic gas sensitive membrane of detection head interface (4) arrival detection head (5) behind the difference frequency signal input signal processor (6) of generation.

2, a kind of device for detecting respiratory that is used to diagnose the early stage of lung cancer according to claim 1, it is characterized in that: described detection head (5) comprising: cut the LiNbO that X propagates at 128 ° of Y ₃The substrate of making (8) is gone up and is made two groups of interdigital electrode passages with the aluminum film, the middle delay line of making two 2.5mm with the aluminum film, the polyisobutylene organic gas sensitive membrane (12) of plating one deck 100nm is as sense channel (10) on a delay line, another not plated film as reference channel (11), the signal of two passage generations is connected to frequency mixer (13) by radio frequency amplifier (9), the difference frequency signal that generation is used to detect, the input difference frequency signal is to signal processor (6).

3, a kind of device for detecting respiratory that is used to diagnose the early stage of lung cancer according to claim 1, it is characterized in that: described detection head interface (4) comprising: capillary outlet shower nozzle (14) is fixed on the heater (15), capillary separation column (3) is connected to organic gas sensitive membrane (12) on the detection head (5) by shower nozzle, put the column type heat-conducting metal cover (16) that an aluminium alloy is made in the outside of shower nozzle, its bottom is fixed on the heater (15), a heat insulation medicated cap (17) is made with heat-barrier material in top at heat-conducting metal cover (16), left-hand thread detection head (5) on medicated cap, thereby form a unsealed air chamber, the semiconductor chilling plate (20) of detection head (5) and 3cm * 3cm is fixed together, the huyashi-chuuka (cold chinese-style noodles) of semiconductor chilling plate (20) and the bottom of detection head (5) are linked to each other by heat conductive silica gel (18), and the hot side of semiconductor chilling plate (20) links to each other by heat conductive silica gel (18) with fin (19).

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