An aerosol exposure system

Abstract

The present invention belongs to the field of aerosol exposure, and specifically relates to an aerosol exposure system. The aerosol exposure system includes a bionic oral cavity and a bionic nasal cavity arranged in parallel, a bionic throat is connected to the downstream intersection of the bionic oral cavity and the bionic nasal cavity, a bionic tracheobronchial tree is connected downstream of the bionic throat, and a bionic lung unit is connected downstream of the bionic tracheobronchial tree; it also includes a thoracic structure, and the bionic tracheobronchial tree and the bionic lung unit are both in the thoracic structure; the upstream of the bionic oral cavity and / or the bionic nasal cavity is connected with an inlet and outlet airway, and the aerosol exposure system also includes a breathing power device for realizing the breathing of each bionic organ. The present invention simulates the real human inhalation and exhalation process, which can not only understand the distribution law of aerosols in the human body, but also study the physiology and damage mechanism of respiratory movement, and provide a research platform for the treatment and damage of exogenous substances.

Description

Technical Field

[0001] The invention belongs to the field of aerosol exposure, and in particular relates to an aerosol exposure system. Background Art

[0002] Breathing is an important process to maintain the balance of oxygen and carbon dioxide in the body and ensure the body's metabolism. The respiratory process is completed by three interconnected and simultaneous links, including pulmonary ventilation, pulmonary ventilation, and gas exchange between blood and tissue cells. Specifically, 1) pulmonary ventilation refers to the gas exchange between the outside air and the alveoli; the organs of pulmonary ventilation include the respiratory tract, alveoli and thorax; the respiratory tract is the channel connecting the alveoli with the outside world; the alveoli are the main place for the exchange of alveolar gas and blood gas; and the rhythmic respiratory movement of the thorax is the driving force for ventilation. 2) Pulmonary ventilation refers to the gas exchange between the alveoli and the blood in the pulmonary capillaries. 3) Gas exchange between blood and tissue cells. When the human body inhales, the diaphragm and intercostal muscles contract, the thorax expands, the top of the diaphragm descends, the negative pressure in the chest cavity decreases, and the fresh air rich in oxygen from the outside world enters the alveoli through the airway, and oxygen enters the capillaries through the alveolar wall. Carbon dioxide produced by tissue metabolism in the capillaries enters the alveoli. When the human body exhales, the diaphragm and intercostal muscles relax, the chest cavity retracts by elasticity, and the carbon dioxide is discharged from the body through the airway. This inhalation and exhalation constitutes a breath. The human body relies on continuous breathing movements to exchange gases, meet the body's metabolic needs, and maintain life.

[0003] Harmful gases, particles and targeted treatment of inhaled drug aerosols in the atmosphere all enter the human body through breathing. A large number of related studies have been conducted to understand the harm of inhaled exogenous substances to the body and the targeted treatment effects of inhaled drugs. Regardless of the type of research, it is necessary to understand the distribution (deposition, suspension) of inhaled exogenous particles in the respiratory tract, so as to obtain the exposure dose in the respiratory tract to further evaluate its exposure internal dose and dose-effect response relationship. At present, there are two main methods for studying aerosol deposition in the lungs, mathematical simulation and physical experiments. In recent years, a large number of scientists have been committed to the research of mathematical simulation. Mathematical simulation mainly uses CT and other scanning technologies and graphic modeling technologies to establish a real 3D model of the human respiratory tract, and uses fluid dynamics (CFD) simulation technology to study the deposition law of aerosols. However, due to the development of computer technology and the limitations of related data, it is difficult to conduct dose-effect studies on specific targets.

[0004] Physical experiments include in vivo experiments and in vitro experiments. In terms of in vivo research, experimental research on humans is subject to ethical restrictions and is usually epidemiological surveys. This method makes it difficult to examine the specific distribution and change process of exogenous substances entering the human body. Regarding experimental research on animals, such as the Chinese patent document with authorization announcement number CN212393856U, which discloses an electronic cigarette aerosol dynamic poison exposure system; due to the racial differences between humans and animals, there is a certain deviation between the data characterizing this aspect of the human body and the actual situation of the human body. In terms of in vitro research, with the continuous development of technology, relevant scholars have established respiratory models in vitro to conduct aerosol distribution research, but usually only a part of the lower respiratory tract is selected, and the upper respiratory tract and lung units and breathing patterns are not examined together. Its authenticity still has a certain deviation from the actual situation; and due to the limitation of the research purpose, the model constructed in vitro is usually not suitable for cell culture units, so it is impossible to conduct relevant dose-effect studies.

[0005] In vitro studies of dose-effect relationships of specific targets usually use in vitro inhalation exposure methods, which mainly include submersion systems and gas-liquid interface exposure systems. Among them, the gas-liquid interface exposure system has the following advantages: 1) It reflects the biological effects of aerosols (gas phase and particle phase) more comprehensively and truly; 2) The fresh aerosol produced by inhalation is directly and real-time exposed, avoiding the influence of factors such as aerosol aging and extraction solvents on the morphology and characteristics of components. It is considered to be a more favorable scientific tool for evaluating in vitro inhalation exposure. At present, the full smoke exposure system represented by Vitrocell does not simulate the exposure environment of the mouth and respiratory system, does not simulate the state of inhalation and exhalation during breathing, and does not simulate the high concentration of carbon dioxide exhaled in exhalation. Therefore, when using the existing in vitro exposure systems on the market, it is difficult to examine the actual exposure of the mouth, nose and cells on the respiratory tract during inhalation and exhalation.

[0006] The Chinese invention patent application with application publication number CN106268545A discloses a method for generating polydisperse small-particle aerosol and measuring its particle size, wherein only the particle size measurement method during deposition is investigated, and no method for investigating the deposition and distribution of the aerosol in the respiratory system is provided.

[0007] The paper "Study on Gas Distribution and Flow in Pulmonary Bronchus" uses mathematical models to examine gas distribution and pressure changes in the bronchial tree. First, although the paper takes into account the asymmetry of the bronchial tree and studies the gas flow in the bronchial tree in both overall and local aspects, the paper is a mathematical model simulation study, which is somewhat different from the distribution and flow of gas in the actual bronchi; secondly, the object of study in this paper is gas, and the mathematical models for studying aerosols and gases are somewhat different and cannot examine the deposition of aerosol particulate matter in the respiratory tract; thirdly, the paper only studies the breathing pattern, and does not give the distribution and flow of special inhalation methods such as inhalation administration. The mathematical algorithms are different for different inhalation methods; finally, the paper only considers the bronchial tubes of the lungs, and does not consider the transmission and distribution of gas in the alveoli, oral cavity, nasal cavity, and throat.

[0008] The paper "Experimental Study on the Deposition of Aerosol Particles in the Human Upper Respiratory Tract Model" uses 3D printing technology to build a complete and realistic human respiratory tract standard model from the mouth to the first three levels of bronchi, uses a vacuum pump to simulate the inhalation movement of the human lungs, and uses the weighing method to examine the deposition of two particle sizes during inhalation in the human upper respiratory tract model. However, the paper did not examine the further material deposition caused by the disturbance of the airflow during the exhalation process; secondly, the paper examines the specific particle size material, and the weighing method in the paper cannot measure the distribution and suspension of gas phase materials in complex aerosols in the respiratory tract wall; finally, the paper did not simulate the further deposition caused by the expansion and contraction of alveolar units to the disturbance of airflow in the respiratory tract. Summary of the invention

[0009] The purpose of the present invention is to provide an aerosol exposure system, which constructs a human-like breathing model to simulate the real inhalation and exhalation process of the human body in vitro, and provides a research platform for understanding the distribution of aerosols in the human body, studying the physiology and injury mechanism of respiratory movements, and the treatment and injury effects of exogenous substances.

[0010] To achieve the above purpose, the technical solution of the aerosol exposure system of the present invention is:

[0011] The aerosol exposure system comprises a bionic oral cavity and a bionic nasal cavity arranged in parallel, wherein a bionic tracheobronchial tree is connected downstream of the bionic oral cavity and the bionic nasal cavity, and a bionic lung unit is connected downstream of the bionic tracheobronchial tree; an inlet and outlet air pipeline is connected upstream of the bionic oral cavity and / or the bionic nasal cavity, and a breathing power device with four working stages is connected to the inlet and outlet air pipeline, wherein in the first working stage, the breathing power device is used to inhale gas from the inlet and outlet air pipeline; in the second working stage, the breathing power device is used to discharge the inhaled gas, so that the gas passes through the bionic oral cavity and / or the bionic nasal cavity and the bionic tracheobronchial tree in sequence and enters the bionic lung unit; in the third working stage, the breathing power device is used to inhale the gas in the bionic lung unit through the bionic tracheobronchial tree, the bionic oral cavity and / or the bionic nasal cavity; in the fourth working stage, the breathing power device is used to discharge the inhaled gas through the inlet and outlet air pipeline.

[0012] The beneficial effect is that the aerosol exposure system of the present invention includes a bionic nasal cavity, a bionic oral cavity, a bionic tracheobronchial tree and a bionic lung unit, which is powered by a respiratory power device to simulate the real human inhalation and exhalation process. It can not only provide an in vitro model for understanding the distribution law of aerosols in the human body, but also provide a research platform for studying the physiology and damage mechanism of respiratory movements, as well as the therapeutic and damaging effects of exogenous substances.

[0013] As a further improvement, a carbon dioxide supply device is connected to the downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the third working stage.

[0014] The beneficial effect is that by adding a carbon dioxide supply device, a certain concentration of carbon dioxide is provided on the one hand, and on the other hand, the volume of exhaled gas is made greater than the volume of inhaled gas, so as to simulate a more realistic breathing process of the human body.

[0015] As a further improvement, at least two bionic lung units are provided, the aerosol exposure system includes a shunt container, the carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

[0016] The beneficial effect is that it is convenient to provide carbon dioxide to each bionic lung unit, and at the same time conforms to the real carbon dioxide exchange method of the human body.

[0017] As a further improvement, an intake branch pipe and an exhaust branch pipe are connected to the upstream of the air inlet and outlet pipelines. Two intake branches are provided, one of the two intake branches is used to connect to a gas source containing clean gas, the other of the two intake branches is used to connect to a test substance source containing aerosol, and the exhaust branch is used to connect to an exhaust gas collector.

[0018] The beneficial effect is: it is conducive to studying more realistic inhalation and exhalation situations. The exhaust gas collector can collect the exhaled gas and detect the exhaled gas through the instrument to obtain a more comprehensive understanding of the breathing process.

[0019] As a further improvement, a humidifying unit is connected to the inlet and outlet air pipelines.

[0020] The beneficial effect is that the humidification unit can humidify the gas entering the inlet and outlet pipes to simulate breathing moist gas.

[0021] As a further improvement, the bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

[0022] The beneficial effects are: simulating a more realistic tracheal-bronchial tree structure, making the breathing process closer to reality, and at least one bionic lung unit is connected downstream with a culture unit, which can be loaded with cultured lung cells, liver cells or other body cells, and the scope of investigation of cell damage is wider.

[0023] As a further improvement, the breathing power device is a piston push-pull device.

[0024] The beneficial effect is that the telescopic push-pull device can easily realize the inhalation and exhalation process of the whole body and can control the gas flow more accurately.

[0025] As a further improvement, the aerosol exposure system further includes a bionic throat disposed at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

[0026] The beneficial effect is that such a design makes the model closer to the real human body.

[0027] As a further improvement, at least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

[0028] The beneficial effect is that such a design makes the model not only closer to the real human body in terms of three-dimensional structure, but also closer to the real human body in terms of physiological structure, making related biological research more realistic.

[0029] To achieve the above purpose, the technical solution of the aerosol exposure system of the present invention is:

[0030] The aerosol exposure system comprises a bionic oral cavity and a bionic nasal cavity arranged in parallel, wherein a bionic tracheobronchial tree is connected downstream of the bionic oral cavity and the bionic nasal cavity, and a bionic lung unit is connected downstream of the bionic tracheobronchial tree; a respiratory power device with four working stages is connected upstream of the bionic tracheobronchial tree, wherein in the first working stage, the respiratory power device is used to inhale gas from the bionic oral cavity and / or the bionic nasal cavity into the respiratory power device; in the second working stage, the respiratory power device is used to push out the inhaled gas, thereby allowing the gas to enter the bionic lung unit through the bionic tracheobronchial tree; in the third working stage, the respiratory power device is used to inhale gas in the bionic lung unit through the bionic tracheobronchial tree; and in the fourth working stage, the respiratory power device is used to discharge the inhaled gas through the bionic oral cavity and / or the bionic nasal cavity.

[0031] The beneficial effect is that the aerosol exposure system of the present invention includes a bionic nasal cavity, a bionic oral cavity, a bionic tracheobronchial tree and a bionic lung unit, which is powered by a respiratory power device to simulate the real human inhalation and exhalation process. It can not only provide an in vitro model for understanding the distribution law of aerosols in the human body, but also provide a research platform for studying the physiology and damage mechanism of respiratory movements, as well as the therapeutic and damaging effects of exogenous substances.

[0032] As a further improvement, a carbon dioxide supply device is connected to the downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the third working stage.

[0033] The beneficial effect is that by adding a carbon dioxide supply device, a certain concentration of carbon dioxide is provided on the one hand, and on the other hand, the volume of exhaled gas is made greater than the volume of inhaled gas, so as to simulate a more realistic breathing process of the human body.

[0034] As a further improvement, at least two bionic lung units are provided, the aerosol exposure system includes a shunt container, the carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

[0035] The beneficial effect is that it is convenient to provide carbon dioxide to each bionic lung unit, and at the same time conforms to the real carbon dioxide exchange method of the human body.

[0036] As a further improvement, the upstream of the bionic oral cavity and / or bionic nasal cavity is connected to an inlet and outlet pipeline, and the upstream of the inlet and outlet pipeline is connected to an intake branch and an exhaust branch. Two intake branches are provided, one of the two intake branches is used to connect to a gas source containing clean gas, the other of the two intake branches is used to connect to a test substance source containing aerosol, and the exhaust branch is used to connect to an exhaust gas collector.

[0037] The beneficial effect is: it is conducive to studying more realistic inhalation and exhalation situations. The exhaust gas collector can collect the exhaled gas and detect the exhaled gas through the instrument to obtain a more comprehensive understanding of the breathing process.

[0038] As a further improvement, an air inlet and outlet pipeline is connected to the upstream of the bionic oral cavity and / or the bionic nasal cavity, and a humidification unit is connected to the air inlet and outlet pipeline.

[0039] The beneficial effect is that the humidification unit can humidify the gas entering the inlet and outlet pipes to simulate breathing moist gas.

[0040] As a further improvement, the bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

[0041] The beneficial effects are: simulating a more realistic tracheal-bronchial tree structure, making the breathing process closer to reality, and at least one bionic lung unit is connected downstream with a culture unit, which can be loaded with cultured lung cells, liver cells or other body cells, and the scope of investigation of cell damage is wider.

[0042] As a further improvement, the breathing power device is a piston push-pull device.

[0043] The beneficial effect is that the telescopic push-pull device can easily realize the inhalation and exhalation process of the whole body and can control the gas flow more accurately.

[0044] As a further improvement, the aerosol exposure system further includes a bionic throat disposed at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

[0045] The beneficial effect is that such a design makes the model closer to the real human body.

[0046] As a further improvement, at least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

[0047] The beneficial effect is that such a design makes the model not only closer to the real human body in terms of three-dimensional structure, but also closer to the real human body in terms of physiological structure, making related biological research more realistic.

[0048] To achieve the above purpose, the technical solution of the aerosol exposure system of the present invention is:

[0049] The aerosol exposure system comprises a bionic oral cavity and a bionic nasal cavity arranged in parallel, wherein a bionic tracheobronchial tree is connected downstream of the bionic oral cavity and the bionic nasal cavity, and a bionic lung unit is connected downstream of the bionic tracheobronchial tree; the aerosol exposure system also comprises a thoracic cavity structure, wherein the bionic lung units are all located in the thoracic cavity structure; the outside of the thoracic cavity structure is connected with a breathing power device having two working stages, wherein in the first working stage, the breathing power device is used to extract gas in the thoracic cavity structure, so that the air pressure in the thoracic cavity structure is reduced, so that the gas enters the bionic lung unit through the bionic nasal cavity and / or the bionic oral cavity, the bionic pharynx, and the bionic tracheobronchial tree; and in the second working stage, the breathing power device is used to inject gas into the thoracic cavity structure, so that the air pressure in the thoracic cavity structure is increased, so that the gas in the bionic lung unit is discharged through the bionic tracheobronchial tree, the bionic pharynx, the bionic nasal cavity, and / or the bionic oral cavity.

[0050] The beneficial effect is that the aerosol exposure system of the present invention includes a bionic nasal cavity, a bionic oral cavity, a thoracic cavity structure, a bionic tracheobronchial tree and a bionic lung unit, which is powered by a respiratory power device to simulate the real human inhalation and exhalation process. It can not only provide an in vitro model for understanding the distribution law of aerosols in the human body, but also provide a research platform for studying the physiology and injury mechanism of respiratory movements, as well as the therapeutic and damaging effects of exogenous substances.

[0051] As a further improvement, a carbon dioxide supply device is connected downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the second working stage.

[0052] The beneficial effect is that by adding a carbon dioxide supply device, a certain concentration of carbon dioxide is provided on the one hand, and on the other hand, the volume of exhaled gas is made greater than the volume of inhaled gas, so as to simulate a more realistic breathing process of the human body.

[0053] As a further improvement, at least two bionic lung units are provided, the aerosol exposure system includes a shunt container, the carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

[0054] The beneficial effect is that it is convenient to provide carbon dioxide to each bionic lung unit, and at the same time conforms to the real carbon dioxide exchange method of the human body.

[0055] As a further improvement, the upstream of the bionic oral cavity and / or bionic nasal cavity is connected to an inlet and outlet pipeline, and the upstream of the inlet and outlet pipeline is connected to an intake branch and an exhaust branch. Two intake branches are provided, one of the two intake branches is used to connect to a gas source containing clean gas, the other of the two intake branches is used to connect to a test substance source containing aerosol, and the exhaust branch is used to connect to an exhaust gas collector.

[0056] The beneficial effect is: it is conducive to studying more realistic inhalation and exhalation situations. The exhaust gas collector can collect the exhaled gas and detect the exhaled gas through the instrument to obtain a more comprehensive understanding of the breathing process.

[0057] As a further improvement, an air inlet and outlet pipeline is connected to the upstream of the bionic oral cavity and / or the bionic nasal cavity, and a humidification unit is connected to the air inlet and outlet pipeline.

[0058] The beneficial effect is that the humidification unit can humidify the gas entering the inlet and outlet pipes to simulate breathing moist gas.

[0059] As a further improvement, the bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

[0060] The beneficial effects are: simulating a more realistic tracheal-bronchial tree structure, making the breathing process closer to reality, and at least one bionic lung unit is connected downstream with a culture unit, which can be loaded with cultured lung cells, liver cells or other body cells, and the scope of investigation of cell damage is wider.

[0061] As a further improvement, the breathing power device is a piston push-pull device.

[0062] The beneficial effect is that the telescopic push-pull device can easily realize the inhalation and exhalation process of the whole body and can control the gas flow more accurately.

[0063] As a further improvement, the aerosol exposure system further includes a bionic throat disposed at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

[0064] The beneficial effect is that such a design makes the model closer to the real human body.

[0065] As a further improvement, at least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

[0066] The beneficial effect is that such a design makes the model not only closer to the real human body in terms of three-dimensional structure, but also closer to the real human body in terms of physiological structure, making related biological research more realistic. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 is a schematic diagram of Example 1 of the aerosol exposure system of the present invention;

[0068] Figure 2is a schematic diagram of Example 2 of the aerosol exposure system of the present invention;

[0069] Figure 3 is a schematic diagram of Example 3 of the aerosol exposure system of the present invention;

[0070] In the figure: 11, electric unit; 12, piston rod; 13, piston cylinder; 14, piston head; 15, inlet and outlet pipes; 16, humidification unit; 17, first valve; 18, second valve; 19, third valve; 20, fourth valve; 21, air source; 22, fifth valve; 23, test substance source; 24, sixth valve; 25, seventh valve; 26, tail gas collector; 27, eighth valve; 28, bionic nasal cavity; 29, nasal cavity culture Unit; 30. Bionic oral cavity; 31. Oral culture unit; 32. Bionic pharynx; 33. Bionic tracheobronchial tree; 34. First lung unit; 35. Side pipeline; 36. Extrapulmonary culture unit; 37. Ventilation device; 38. Carbon dioxide supply device; 39. Intrapulmonary culture unit; 40. Second lung unit; 41. Diversion container; 42. Third lung unit; 43. Thoracic structure; 44. Control unit; 45. Carbon dioxide pipeline. DETAILED DESCRIPTION

[0071] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention, that is, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The components of the embodiments of the present invention described and shown in the drawings herein can be arranged and designed in various different configurations.

[0072] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work are within the scope of protection of the present invention.

[0073] It should be noted that the terms such as "first" and "second" and other relational terms that may appear are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, terms such as "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "including one..." do not exclude the existence of other identical elements in the process, method, article or device including the elements. In addition, the terms "front", "back", "up", "down", "left" and "right" are based on the orientation and positional relationship shown in the accompanying drawings, only for the convenience of describing the present invention, rather than indicating that the device or component referred to must have a specific orientation, and therefore cannot be understood as a limitation of the present invention.

[0074] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0075] Example 1 of the aerosol exposure system of the present invention:

[0076] like Figure 1 As shown, the aerosol exposure system includes a bionic oral cavity 30 and a bionic nasal cavity 28 arranged in parallel, wherein the bionic oral cavity 30 is used to place an oral cavity culture unit 31, and the bionic nasal cavity 28 is used to place a nasal cavity culture unit 29. A bionic throat 32 is connected to the downstream intersection of the bionic oral cavity 30 and the bionic nasal cavity 28, and a bionic trachea-bronchial tree 33 is connected to the downstream of the bionic throat 32, and a bionic lung unit is connected to the downstream of the bionic trachea-bronchial tree 33. There are three bionic lung units, namely, a first lung unit 34, a second lung unit 40, and a third lung unit 42. The second lung unit 40 is used to place an intrapulmonary culture unit 39, and an extrapulmonary culture unit 36 ​​is connected to the downstream of the first lung unit 34, and the extrapulmonary culture unit 36 ​​is connected to the bionic trachea-bronchial tree 33 through a side pipe 35. Among them, the volume of the third lung unit 42 is equivalent to the total volume of the first lung unit 34 and the second lung unit 40 to simulate the left lung and the right lung.

[0077] In this embodiment, the aerosol exposure system further includes a chest structure 43 , and the bionic tracheobronchial tree 33 and the bionic lung unit are both located in the chest structure 43 .

[0078] In this embodiment, the downstream of the three bionic lung units are connected to the diversion container 41 through the carbon dioxide pipeline 45, and the diversion container 41 is connected to the carbon dioxide supply device 38. Among them, each carbon dioxide pipeline 45 is provided with a ventilation device 37 and a control valve.

[0079] In this embodiment, the upstream of the bionic oral cavity 30 and the bionic nasal cavity 28 is connected to the inlet and outlet pipeline 15. Specifically, two downstream branches are provided downstream of the inlet and outlet pipeline 15, and the two downstream branches are respectively connected to the bionic oral cavity 30 and the bionic nasal cavity 28, and the second valve 18 and the eighth valve 27 are respectively provided on the two downstream branches. An exhaust branch and two intake branches are provided in parallel upstream of the inlet and outlet pipeline 15. The exhaust branch is connected to the exhaust gas collector 26, and the seventh valve 25 is provided on the exhaust branch; one of the two intake branches is connected to the air source 21, and the other of the two intake branches is connected to the test substance source 23, and the fifth valve 22 and the sixth valve 24 are respectively provided on the two intake branches. In other embodiments, two inlet and outlet pipelines are provided, and the two inlet and outlet pipelines are respectively connected to the upstream of the bionic oral cavity and the bionic nasal cavity, and piston push-pull devices are respectively provided on the two inlet and outlet pipelines to realize different oral and nasal inhalation and oral and nasal exhalation modes.

[0080] In this embodiment, the inlet and outlet pipelines 15 are further provided with a first valve 17 and a fourth valve 20, and the inlet and outlet pipelines 15 are connected with a piston push-pull device and a humidifying unit 16 between the first valve 17 and the fourth valve 20. Among them, a third valve 19 is provided between the piston push-pull device and the inlet and outlet pipelines 15, and a control valve is provided between the humidifying unit 16 and the inlet and outlet pipelines 15.

[0081] like Figure 1 As shown, the piston push-pull device includes a piston cylinder 13, a piston and an electric unit 11. The piston includes a piston head 14 and a piston rod 12. The outer diameter of the piston head 14 is consistent with the inner diameter of the piston cylinder 13 to ensure that there is no air leakage between the piston head 14 and the piston cylinder 13. One end of the piston rod 12 is connected to the center of the piston head 14, and the other end of the piston rod 12 is connected to the electric unit 11. Among them, the piston rod 12 can be a straight rod or a curved rod. The piston is pushed and pulled by the electric unit 11 to allow the piston cylinder 13 to inhale and exhale air. In this embodiment, the piston push-pull device constitutes a breathing power device. In other embodiments, the breathing power device can be a vacuum generator integrated device of the prior art.

[0082] In this embodiment, the piston cylinder 13 is made of transparent glass, transparent plastic, metal, etc. When the material is transparent, the internal situation can be observed; the main structure of the piston head 14 is made of a hard material, such as stainless steel and other metals, and a sealing ring is provided on its outer peripheral surface to ensure air tightness; the piston rod 12 is made of a hard material, such as stainless steel and other metals.

[0083] In this embodiment, the electric unit 11 is controlled by the control unit 44, the measuring range of the piston cylinder 13 is 0-5000mL, the accuracy is 0.05-5mL, the frequency is 0-100 times / min, the push-pull waveform can be bell-shaped, sinusoidal, triangular wave, square wave, breathing waveform and custom waveform, the pulling time is 0-60s, the accuracy is 0.01s, the pushing time is 0-60s, the accuracy is 0.01s, the push-pull time interval is 0-30min, the accuracy is 0.01s, the interval between two push-pull times is 0-2h, the accuracy is 0.01s, the push-pull start can be controlled by time, pressure, and capacity, and the push-pull flow rate is 0-120L / min.

[0084] In the present embodiment, the humidification unit 16 is used to humidify the gas, and the humidification unit 16 may or may not be provided according to the experimental requirements. Specifically, the humidification unit 16 is a humidifier, which can directly provide atomized water vapor with a certain humidity, and the atomized water vapor enters the oral and nasal direction pipelines together with the inhaled gas. Among them, the humidifier can provide water vapor with a certain humidity according to the time frequency, and the realization of the time frequency can be achieved by controlling a time-controlled switch or a time-controlled solenoid valve. In other embodiments, the humidification unit is similar to the buoy-type oxygen inhaler in the prior art, and the inhaled gas is introduced into a liquid environment, so that the gas is fully humidified in the liquid environment and then overflows from the liquid environment into the oral and nasal direction pipelines.

[0085] In this embodiment, the above-mentioned valves and control valves are all solenoid valves to facilitate automatic control.

[0086] In this embodiment, the bionic nasal cavity 28 is based on the target human nasal cavity image obtained by computer tomography imaging technology. According to the different cross-sectional views of the nasal cavity obtained, the three-dimensional graphic structure of the nasal cavity is reconstructed using graphic processing software (such as Mimics software). Combined with the structural properties of the nasal cavity and the requirements of the exposure culture device (embeddable and placed culture structure, easy to operate, and good air tightness), the three-dimensional graphic structure is reasonably decomposed into four parts, namely, the nose end, the throat end structure, the culture unit placement structure, the nasal cavity peripheral structure, and the connection structure. Then, the structure is made and connected using 3D printing technology or molding. The material is metal, glass, silicone resin, plastic, polycaprolactone, polylactic acid-glycolic acid copolymer, etc. that can be used for disinfection and sterilization, or the material is 3D cell biomaterial.

[0087] In this embodiment, the bionic oral cavity 30 is based on the target human oral cavity image obtained by computer tomography imaging technology. According to the different cross-sectional views of the oral cavity obtained, the three-dimensional graphic structure of the oral cavity is reconstructed using graphic processing software (such as Mimics software). Combined with the oral structure properties and the requirements of the exposure culture device (embeddable and placed culture structure, easy to operate, good airtightness), the three-dimensional graphic structure is reasonably decomposed into four parts, namely, the oral end and throat end structure, the culture unit placement structure, the oral peripheral structure, and the connection structure. Then, the structure is made and connected using 3D printing technology or molding. The material is metal, glass, silicone resin, plastic, polycaprolactone, polylactic acid-glycolic acid copolymer, etc. that can be used for disinfection and sterilization, or the material is 3D cell biomaterial.

[0088] In this embodiment, the bionic throat 32 is based on the target human throat image obtained by computer tomography imaging technology. According to the different cross-sectional views of the throat obtained, the three-dimensional graphic structure of the throat is reconstructed using graphic processing software (such as Mimics software). Combined with the throat structure properties and the requirements of the exposure culture device (embeddable and placed culture structure, easy to operate, good air tightness), the three-dimensional graphic structure is reasonably decomposed into four parts, namely, the mouth end, nose end, tracheal tree end structure, culture unit placement structure, throat peripheral structure, and connection structure. Then, the structure is made and connected using 3D printing technology or molding method. The material is metal, glass, silicone resin, plastic, polycaprolactone, polylactic acid-glycolic acid copolymer, etc. that can be used for disinfection and sterilization, or the material is 3D cell biomaterial.

[0089] In this embodiment, the bionic tracheobronchial tree 33 is based on the target human tracheal tree image obtained by computer tomography imaging technology. According to the different cross-sectional views of the tracheal tree obtained, the three-dimensional graphic structure of the tracheal tree is reconstructed using graphic processing software (such as Mimics software). Combined with the structural properties of the tracheal tree, the requirements of the exposure device (embeddable, culture unit placement, easy operation, good airtightness) and the purpose of the experiment, the three-dimensional graphic structure is reasonably decomposed into four parts, namely, the throat end and lung unit end structure, the culture unit placement structure, the tracheal tree peripheral structure, and the connection structure. Then, the structure is made and connected using 3D printing technology or molding. The material is metal, glass, silicone resin, plastic, polycaprolactone, polylactic acid-glycolic acid copolymer, etc. that can be used for disinfection and sterilization, or the material is 3D cell biomaterial. Figure 1 The bionic tracheobronchial tree 33 in the embodiment is from level 0 to the left level 1 bronchus and the right level 2 bronchus. In other embodiments, the bionic tracheobronchial tree may be multi-level.

[0090] In this embodiment, the bionic lung unit is used to simulate the expansion and contraction of the lung during breathing. The basic unit of the bionic lung unit is composed of an expandable and contractible bubble structure, and two vents are provided at both ends of the bubble structure, one of the two vents is connected to the end of the bronchus, and the other of the two vents is connected to the carbon dioxide pipeline 45 or the extrapulmonary culture unit 36. Depending on the purpose of use, the material, shape, size, etc. of each bionic lung unit are different.

[0091] In the present embodiment, the venting device 37 is used to realize the supply of gas to the liquid layer. The venting device 37 is composed of a shell and a membrane material. The shell can be of various shapes. The membrane material is on a cross section somewhere in the shell, and the optimal shape of the cross section here is circular. There are gas ports and liquid ports at both ends of the shell. The edge where the membrane material contacts the inner cross section of the shell has a rubber ring or a clamping structure, so that the membrane material is well extended and the periphery and the inner surface of the shell are airtight and airtight. The membrane material is a hydrophobic breathable membrane, such as polypropylene, tetrafluoroethylene, fluorine-containing polymers and other materials. The outer surface of the gas port has threads, and when connected to the pipeline, it is better to ensure airtightness. The material of the shell can be metal, plastic, etc.

[0092] In this embodiment, the carbon dioxide supply device 38 provides a certain concentration of carbon dioxide to the mouth, nose, throat and respiratory tract according to the exhalation frequency. The carbon dioxide concentration range in the exhaled air is consistent with the actual human body or the purpose of the experiment. The carbon dioxide supply device 38 is mainly composed of a carbon dioxide supply device, a filtering device and an exhalation power pump. The carbon dioxide supply device generates carbon dioxide of different concentrations and volumes according to computer settings, which can be achieved according to different ratios of air and pure carbon dioxide. The generated gas passes through the filtering device to ensure sterility. The exhalation power pump continuously or intermittently provides carbon dioxide to the outside according to the set frequency, flow rate, etc. of the computer.

[0093] In this embodiment, the control unit 44 controls and monitors the control module and the sensing module of the entire exposure system through software, which is mainly achieved by setting parameters, monitoring parameters and alarm parameters.

[0094] In this embodiment, the chest structure 43 is a closed cavity with a certain degree of expansion and contraction to simulate the expansion and contraction of the lungs and chest during the breathing process. The expansion and contraction of this part mainly depends on the change of gas during the breathing process. When it uses a material with poor expansion and contraction properties, it is used to simulate the weakness of the chest muscles of the body.

[0095] The aerosol exposure system is placed in an environment with suitable temperature to simulate the breathing process of the body as follows:

[0096] The first gas storage process: In the parameter setting of the piston push-pull device, the reset state is that the piston is at the outlet end of the piston cylinder 13. When the piston is pulled for the first time, it is the first gas storage process, the third valve 19, the fourth valve 20 and the fifth valve 22 are opened, and the first valve 17 is closed. The electric unit 11 in the piston push-pull device starts at the set start time, and the gas extraction time T 抽 , air extraction volume V 抽 , the gas in the gas source 21 is drawn into the piston cylinder 13, and when the gas volume reaches the set V 抽 When the gas storage process is finished, the third valve 19, the fourth valve 20 and the fifth valve 22 are closed. At this time, the gas in the gas source 21 is clean air or a mixed gas with a certain volume ratio. The above description is about sucking the gas source 21 into the piston cylinder 13.

[0097] When the inhalation is accompanied by the test substance contamination, the gas source 21 and the test substance source 23 are sucked into the piston cylinder 13. According to the experimental needs, the gas volume ratio R of the gas source 21 and the test substance source 23 is set, and the flow rate and outflow time of the gas source 21 and the test substance source 23 are controlled by a computer.

[0098] When only the test substance is inhaled during inhalation, the test substance source 23 is inhaled into the piston cylinder 13, and the flow rate and outflow time of the test substance source 23 are controlled by a computer according to experimental needs.

[0099] Simulate the inhalation process of the body: When the piston is pushed for the first time, it simulates the inhalation process of the body. The time interval from the end of the gas storage process to the start of inhalation is T 隔1 According to the set inhalation mode (mouth inhalation, nasal inhalation, mouth + nose inhalation, etc.), the first inhalation start time (after T 隔1 After), the first inspiratory time T 吸 The third valve 19, the first valve 17 and the control valve of the humidification unit 16 are opened, the fourth valve 20 is closed, the closing or opening state of the second valve 18 and the eighth valve 27 and the gas proportion or volume passing through each bionic unit are controlled according to the set inhalation mode, and the lower port of the bionic lung unit is in a closed state. The electric unit 11 in the piston push-pull device is controlled according to the set first inhalation start time and the first inhalation time T 吸 , Inspiratory volume V 吸 , inhalation waveform and inhalation mode, the gas in the piston cylinder 13 enters each bionic lung unit in sequence through the bionic nasal cavity 28 and / or the bionic oral cavity 30, the bionic throat 32, and the bionic tracheobronchial tree 33. The humidification unit 16 provides a certain concentration of water vapor to the gas during this process.

[0100] Simulate the exhalation process of the body: When the piston is pulled for the second time, it simulates the exhalation process of the body. The time interval from the end of the inhalation process to the beginning of the exhalation process is T屏 , that is, the breath holding time. According to the set exhalation mode (mouth exhalation, nose exhalation, mouth + nose exhalation, etc.), the first exhalation start time (after T 屏 After), the first exhalation time T 呼 , the control valve of the humidification unit 16 is closed, the lower port of each bionic lung unit is in an open state, the closing or opening state of the second valve 18 and the eighth valve 27 and the gas ratio or volume passing through each bionic unit are controlled according to the set inhalation mode. The electric unit 11 in the piston push-pull device is controlled according to the set first exhalation start time, the first exhalation time T 呼 , expiratory volume V 呼 , exhalation waveform and exhalation mode, the gas in each bionic lung unit is sucked into the piston cylinder 13 through the bionic tracheobronchial tree 33, the bionic throat 32, the bionic oral cavity 30, and the bionic nasal cavity 28 to complete the exhalation process.

[0101] During the exhalation process, the carbon dioxide supply device 38 supplies gas to the shunt container 41 according to the first exhalation start time, the first exhalation time, the exhaled carbon dioxide concentration, the exhaled carbon dioxide volume, and the exhalation waveform; at this time, the control valves of the shunt container 41 are in a corresponding open state according to the set first exhalation start time, the first exhalation time, and the gas volume distribution ratio in each direction, so as to control the gas volume passing through each within the exhalation time. Since the lower port of each bionic lung unit is in an open state, the carbon dioxide gas supplied by the carbon dioxide supply device reaches each bionic lung unit through the shunt container 41 and the ventilation device 37, and then is inhaled into the piston cylinder 13 together with the gas in the bionic lung unit, completing the process of exhaling with carbon dioxide.

[0102] The first gas discharge process: When the piston is pushed for the second time, it is the first gas discharge process. The time interval from the end of the exhalation process to the start of exhaust is T 隔2 The first valve 17, the fifth valve 22 and the sixth valve 24 are in a closed state, the third valve 19, the fourth valve 20 and the seventh valve 25 are in an open state, and according to the exhaust volume V 排 , Exhaust waveform, Exhaust time T 排 , the gas in the piston cylinder 13 is discharged into the exhaust gas collector 26.

[0103] The time interval from the end of the first gas discharge to the start of the second gas storage is T 隔3 In T 隔3 After that, the next breathing process can be carried out according to the settings.

[0104] The system completes the simulation of two consecutive breathing processes of the human body and experiences the first gas reserve time T 抽 , the interval time from the end of gas reserve to the start of inhalation T 隔1 , inspiratory time T吸 , breath holding time T 屏 , exhalation time T 呼 , the time interval T from the end of the exhalation process to the start of exhaust 隔2 , exhaust time T 排 , the time interval T from the end of the first exhaust to the beginning of the second gas storage 隔3 ; Second gas reserve time T 抽’ , the interval time from the end of gas reserve to the start of inhalation T 隔1’ , inspiratory time T 吸’ , breath holding time T 屏’ , exhalation time T 呼’ , the time interval T from the end of the exhalation process to the start of exhaust 隔2’ , exhaust time T 排’ Among them, the interval between two consecutive breaths is T 呼吸间隔 =T 隔2 +T 排 +T 隔3 +T 抽’ During the above time course, according to the experimental needs, pause time and corresponding inhalation and exhalation volumes were set in each time period to simulate special situations such as multiple small inhalations and multiple small exhalations of the human body.

[0105] In addition, the inhalation and exhalation process of the extrapulmonary culture unit 36 ​​connected here is as follows: the gas layer of the extrapulmonary culture unit 36 ​​has no expansion and contraction effect. In order to maintain the air pressure balance inside the extrapulmonary culture unit 36 ​​and reduce the damage to cells caused by the change of air pressure during inhalation and exhalation, the inhalation and exhalation process is completed by the following contents. The upper part of the extrapulmonary culture unit 36 ​​is connected to the first lung unit 34. According to the above-mentioned breathing process, before the end of inhalation, the air inlet direction of the extrapulmonary culture unit 36 ​​connected to the first lung unit 34 is always in a closed state, and the side pipe 35 is in a closed state; after the end of inhalation, the air inlet direction connected to the first lung unit 34 is always in an open state, and at the beginning of exhalation, the upper port of the first lung unit 34 is in a closed state, and the side pipe is in an open state. Under the action of exhalation power, the gas in the first lung unit 34 and the gas in the extrapulmonary culture unit 36 ​​enter the bionic tracheobronchial tree 33 through the side pipe 35, and then are discharged from the bionic tracheobronchial tree 33.

[0106] Using the aerosol exposure system of the present invention to investigate the damage of simulated oral and nasal breathing to lung cells

[0107] 1) Set up the aerosol exposure system according to Figure 1 The second lung unit 40 and the extra-lung culture unit 36 ​​are connected in a manner to simulate the oral and nasal breathing mode to ensure the sterility of the system. The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells.

[0108] 2) Set the relevant parameters of the breathing process of the simulated body when breathing through the mouth and nose as 1 breathing cycle on the computer. After setting N breathing cycles according to the experimental needs, start the main ventilation switch to start the breathing movement of the aerosol exposure system.

[0109] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0110] The oral and nasal breathing pattern simulated by this system is usually used to simulate the state of the body when it has no spontaneous breathing.

[0111] Using the aerosol exposure system of the present invention to investigate the damage of the target test substance to lung cells in the mouth-nose breathing mode

[0112] 1) When investigating the damage of target aerosols such as PM2.5, hazardous gases, drug aerosols, tobacco smoke, etc. in the environment to lung cells during mechanical ventilation, the generating device of PM2.5, hazardous gases, drug aerosols, tobacco smoke, etc. is used as the test substance source 23, and the opening frequency and opening ratio of the electromagnetic valves of the fifth valve 22 and the sixth valve 24 are adjusted according to the inhalation frequency and inhalation ratio of the target test substance, that is, the volume of the target test substance allowed to enter.

[0113] 2) Then, the aerosol exposure system was set up according to Figure 1 The second lung unit 40 and the extra-lung culture unit 36 ​​are connected in a manner to simulate the oral and nasal breathing mode. The device is ensured to be sterile. The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells.

[0114] 3) Set the relevant parameters of the breathing process when simulating the mouth and nose breathing mode of the body to 1 breathing cycle on the computer, and set the frequency, volume, and interval between the inhaled target gas and breathing for each inhalation of the target gas. After setting N breathing cycles and M inhaled target gases according to the experimental needs, start the main ventilation switch to start the inhalation and exhalation movements of the aerosol exposure system simulating the mouth and nose breathing mode. There are two forms of inhalation of target gas: 1) When the inhalation of target gas is accompanied by the inhalation process of breathing, set the ratio of the inhaled target gas to the volume of air entering, and at which breath the target gas is inhaled. 2) When the target gas is inhaled alone without breathing, set the inhalation volume of the target gas, at which point in time to inhale and other parameters.

[0115] 4) After N respiratory cycles and M inhalations of the target gas, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0116] Using the aerosol exposure system of the present invention to investigate the damage to oral / nasal cells in the oral and nasal breathing mode

[0117] 1) Set up the aerosol exposure system according to Figure 1 The nasal cavity culture unit 29 and the oral cavity culture unit 31 are connected in a manner to simulate the oral and nasal breathing mode. The device is ensured to be sterile. The nasal cavity culture unit 29 and the oral cavity culture unit 31 are loaded with cultured cells.

[0118] 2) Set the relevant parameters of the breathing process of the simulated oral and nasal breathing to 1 breathing cycle on the computer. After setting N breathing cycles according to the experimental needs, start the main ventilation switch to start the breathing movement of the aerosol exposure system in the simulated oral and nasal breathing mode.

[0119] 3) After N respiratory cycles, the nasal culture unit 29 and the oral culture unit 31 are removed, and the cultured cells and supernatant loaded in the nasal culture unit 29 and the oral culture unit 31 are collected and analyzed using relevant cell damage analysis methods.

[0120] The aerosol exposure system of the present invention is used to investigate the effects of the mouth and nose breathing mode on the pressure, humidity, oxygen concentration and carbon dioxide concentration in the mouth and respiratory system

[0121] 1) Set up the aerosol exposure system according to Figure 1 Connect the monitoring unit (pressure, humidity, oxygen concentration, carbon dioxide concentration) at the position of the mouth and respiratory system to be examined.

[0122] 2) Set the relevant parameters of the breathing process of the simulated oral and nasal breathing to 1 breathing cycle on the computer. After setting N breathing cycles according to the experimental needs, start the main ventilation switch to start the breathing movement of the aerosol exposure system in the simulated oral and nasal breathing mode.

[0123] 3) After N breathing cycles, the computer records and analyzes the time variation trend of pressure, humidity, oxygen concentration and carbon dioxide concentration at the target position during the breathing cycle.

[0124] Usually, when examining such indicators, the following methods can be used according to the target position to be examined: 1) connect a branch pipeline and connect a monitoring unit to the branch pipeline; 2) drill a hole in the bionic structure at the target position to be examined, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole; 3) when reconstructing the 3D graphics of the bionic structure, reserve a hole for the monitoring unit insertion position according to the target position to be examined, and then perform 3D printing, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole.

[0125] Example 2 of the aerosol exposure system of the present invention:

[0126] The difference between this embodiment and embodiment 1 is that in this embodiment, Figure 2 As shown, the piston push-pull device is connected to the connection position of the bionic throat 32 and the bionic tracheal-bronchial tree 33. Among them, the inlet and outlet pipes 15 are not connected to the bionic nasal cavity 28. In other embodiments, the inlet and outlet pipes can be connected to both the bionic oral cavity and the bionic nasal cavity.

[0127] In this embodiment, the piston push-pull device constitutes a breathing power device. In other embodiments, the breathing power device can be a vacuum generator integrated device of the prior art.

[0128] Simulate the oral and nasal inhalation process of the body: In the parameter setting of the piston push-pull device, the reset state is that the piston is at the outlet end of the piston cylinder 13, and the bionic lung unit is in a contracted recovery state. According to the set inhalation mode (oral inhalation, nasal inhalation, oral + nasal inhalation, etc.), the eighth valve 27 upstream and downstream of the bionic nasal cavity 28, the second valve 18, the fifth valve 22 and the sixth valve 24 upstream and downstream of the bionic oral cavity 30 are in a closed or open state according to the set inhalation mode, the first valve 17 is in a closed state, and the third valve 19 and the fourth valve 20 are in an open state. When the piston is pulled for the first time, in order to simulate the oral and nasal inhalation process of the body, the electric unit 11 starts at the set start time, and the inhalation time T 吸1 , inspiratory volume V 吸1 , inhalation waveform, pulls the aerosol outside the mouth and nose into the piston cylinder 13, and when the gas volume reaches the set V 吸1 When the oral and nasal inhalation process is completed, the third valve 19 is closed.

[0129] Simulate the inhalation process of the tracheal tree and lung unit: experience pause time T 停1 After that, when the piston is pushed for the first time, the inhalation process of the bionic tracheobronchial tree 33 and the bionic lung unit is simulated. According to the setting of the first push start time (after T 停1 After), inspiratory time T 吸2 , inspiratory volume V 吸2 , inhalation waveform, close the fourth valve 20, open the third valve 19 and the first valve 17, and close the lower port of each bionic lung unit. The electric unit 11 follows the set inhalation time T 吸2 , inspiratory volume V 吸2 , the inhalation waveform pushes the gas from the piston cylinder 13 into the bionic tracheobronchial tree 33 and into each bionic lung unit. The volume of the bionic lung unit increases continuously with the extension of the inhalation time.

[0130] Simulated breath holding: The time interval from the end of the inhalation process to the beginning of the exhalation process is T 屏 , that is, the breath-holding time.

[0131] Simulate the exhalation process of the tracheal tree and lung unit: When the piston is pulled for the second time, it simulates the exhalation process of the tracheal tree and lung unit of the body. The first exhalation start time (after T 屏 After), the first tracheal tree exhalation time T 呼1 , the fourth valve 20 is in a closed state, the first valve 17, the third valve 19 and the lower ports of each bionic lung unit are in an open state, and the electric unit 1 is in accordance with the set first exhalation start time, first exhalation time, exhalation volume V 呼1 , exhalation waveform, the aerosol in the bionic lung unit and the bionic tracheobronchial tree 33 is inhaled into the piston cylinder 13, when T 呼1 When the time is up, the third valve 19 is closed. At this time, the volume of the bionic lung unit decreases continuously as the exhalation time increases.

[0132] Simulate the exhalation process of mouth and nose: experience pause time T 停2 After that, when the piston is pushed for the second time, it simulates the exhalation process from the mouth and nose. According to the setting of the second exhalation start time (after T 停2 After), exhalation time T 呼2 , expiratory volume V 呼2 , inhalation waveform, according to the set exhalation mode (mouth exhalation, nasal exhalation, mouth + nose exhalation, etc.), the first valve 17 is in a closed state, the third valve 19 and the fourth valve 20 are in an open state, the eighth valve 27 upstream and downstream of the bionic nasal cavity 28, the second valve 18 upstream and downstream of the bionic oral cavity 30, the fifth valve 22 and the sixth valve 24 are in a closed or open state according to the set inhalation mode, and control the gas volume passing through each within the exhalation time. The electric unit 11 sets the second exhalation start time and the second exhalation time T according to the set 呼2 , expiratory volume V 呼2 , exhalation waveform, the gas is pushed into the mouth and nose direction by the piston cylinder 13, and is discharged into the exhaust collector 26 through the bionic oral cavity 30 through the set open valve and / or discharged into the atmosphere through the bionic nasal cavity 28.

[0133] Simulate the carbon dioxide exhalation process: during the exhalation process, the carbon dioxide supply device 38 supplies gas to the shunt container 41 according to the first exhalation start time, the first exhalation time, the exhaled carbon dioxide concentration, the exhaled carbon dioxide volume, and the exhalation waveform; at this time, the valve of the shunt container 41 is in a corresponding open state according to the set first exhalation start time, the first exhalation time, and the gas volume distribution ratio in each direction, so as to control the gas volume passing through each direction within the exhalation time; the lower port of the bionic lung unit is in an open state, and the gas supplied by the carbon dioxide supply device 38 enters the bionic lung unit through the shunt container 41 and the ventilation device 37, and then reaches the piston cylinder 13 together with the gas in the bionic lung unit, completing the process of exhaling carbon dioxide.

[0134] Simulated breathing interval: The time interval from the end of the first exhalation to the beginning of the second inhalation is the breathing interval T 间隔 In T 间隔 After that, the next breathing process can be carried out according to the settings.

[0135] The total inhalation time T during the simulated human breathing process 吸 =T 吸1 +T 停1 +T 吸2 , breath holding time T 屏 , exhalation time T 呼 =T 呼1 +T 停2 +T 呼2 , breathing interval T 间隔 During the above time course, according to the experimental needs, pause time and corresponding inhalation and exhalation volumes were set in each time period to simulate special situations such as multiple small inhalations and multiple small exhalations of the human body.

[0136] In addition, the inhalation and exhalation process of the extrapulmonary culture unit 36 ​​connected here is as follows: the gas layer of the extrapulmonary culture unit 36 ​​has no expansion and contraction effect. In order to maintain the air pressure balance inside the extrapulmonary culture unit 36 ​​and reduce the damage to cells caused by the change of air pressure during inhalation and exhalation, the inhalation and exhalation process is completed by the following contents. The upper part of the extrapulmonary culture unit 36 ​​is connected to the first lung unit 34. According to the above-mentioned breathing process, before the end of inhalation, the air inlet direction of the extrapulmonary culture unit 36 ​​connected to the first lung unit 34 is always in a closed state, and the side pipe 35 is in a closed state; after the end of inhalation, the air inlet direction connected to the first lung unit 34 is always in an open state, and at the beginning of exhalation, the upper port of the first lung unit 34 is in a closed state, and the side pipe is in an open state. Under the action of exhalation power, the gas in the first lung unit 34 and the gas in the extrapulmonary culture unit 36 ​​enter the bionic tracheobronchial tree 33 through the side pipe 35, and then are discharged from the bionic tracheobronchial tree 33.

[0137] Using the aerosol exposure system of the present invention to investigate the damage of the target test substance to lung cells during simulated breathing

[0138] 1) When investigating the damage of target aerosols such as PM2.5, harmful gases, drug aerosols, tobacco smoke, etc. in the environment to lung cells during simulated breathing, the generating device of PM2.5, harmful gases, drug aerosols, tobacco smoke, etc. is used as the test substance source 23, and the opening frequency and opening ratio of the fifth valve 22 and the sixth valve 24 to the solenoid valve are adjusted according to the inhalation frequency and inhalation ratio of the target test substance, that is, the volume of the target test substance allowed to enter.

[0139] 2) Then, the aerosol exposure system was set up according to Figure 2The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells.

[0140] 3) Set the relevant parameters for simulating the breathing process of the body on the computer to 1 breathing cycle, and set the frequency, volume, and interval between the inhaled target gas and breathing for each inhalation of the target gas. After setting N breathing cycles and M inhaled target gases according to the experimental needs, start the main breathing switch to start the breathing and inhalation movement of the aerosol exposure system. There are two forms of inhalation of target gas: 1) When the inhalation of target gas is accompanied by the inhalation process of breathing, set the ratio of the inhaled target gas to the volume of air entering, and at which breath the target gas is inhaled. 2) When the target gas is inhaled alone without breathing, set the inhalation volume of the target gas, at which point in time to inhale and other parameters.

[0141] 4) After N respiratory cycles and M inhalations of the target gas, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0142] Using the aerosol exposure system of the present invention to investigate the damage to oral / nasal cells during simulated breathing

[0143] 1) Set up the aerosol exposure system according to Figure 2 The nasal cavity culture unit 29 and the oral cavity culture unit 31 are loaded with cultured cells.

[0144] 2) Set the relevant parameters of the breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to the experimental needs, start the main breathing switch to make the aerosol exposure system start breathing movement.

[0145] 3) After N respiratory cycles, the nasal culture unit 29 and the oral culture unit 31 are removed, and the cultured cells and supernatant loaded in the nasal culture unit 29 and the oral culture unit 31 are collected and analyzed using relevant cell damage analysis methods.

[0146] The aerosol exposure system of the present invention is used to investigate the effects of simulated breathing on the pressure, humidity, oxygen concentration and carbon dioxide concentration in the mouth and respiratory system.

[0147] 1) Set up the aerosol exposure system according to Figure 2 Connect the monitoring unit (pressure, humidity, oxygen concentration, carbon dioxide concentration) at the location to be examined in the mouth and respiratory system.

[0148] 2) Set the relevant parameters of the simulated breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to the experimental needs, start the main breathing switch to make the aerosol exposure system start breathing movement.

[0149] 3) After N breathing cycles, the computer records and analyzes the time variation trend of pressure, humidity, oxygen concentration and carbon dioxide concentration at the target position during the breathing cycle.

[0150] Usually, when examining such indicators, the following methods can be used according to the target position to be examined: 1) connect a branch pipeline and connect a monitoring unit to the branch pipeline; 2) drill a hole in the bionic structure at the target position to be examined, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole; 3) when reconstructing the 3D graphics of the bionic structure, reserve a hole for the monitoring unit insertion position according to the target position to be examined, and then perform 3D printing, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole.

[0151] Using the aerosol exposure system of the present invention to investigate the damage of pulmonary cells caused by atelectasis on one side during simulated breathing

[0152] 1) Set up the aerosol exposure system according to Figure 2 The second lung unit 40 and the extrapulmonary culture unit 36 ​​are loaded with cultured cells. According to the experimental requirements, the bronchial tube on one side is completely closed or partially closed to simulate the state of atelectasis on one side.

[0153] 2) Set the relevant parameters of the simulated breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to the experimental needs, start the main ventilation switch to make the aerosol exposure system start breathing movement.

[0154] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0155] Using the aerosol exposure system of the present invention to investigate the damage of mechanical ventilation at the mouth and nose to lung cells simulating breathing

[0156] 1) Set up the aerosol exposure system according to Figure 2 The second lung unit 40 and the extrapulmonary culture unit 36 ​​are loaded with cultured cells. The ventilator is connected at the mouth or nose according to the breathing mode, and the ventilator parameters are set.

[0157] 2) Set the relevant parameters of the simulated breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to the experimental needs, start the ventilation master switch to start the breathing movement of the aerosol exposure system. Among them, the breathing trigger of the commercial ventilator has pressure trigger and time trigger. The pressure trigger performs ventilation according to the pressure change in the set simulated breathing process, and the time trigger determines whether the frequency rhythm is consistent with the simulated breathing process according to the time requirements.

[0158] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0159] Using the aerosol exposure system of the present invention to investigate the damage of chest compression to lung cells simulating breathing

[0160] 1) Set up the aerosol exposure system according to Figure 2 The second lung unit 40 and the extrapulmonary culture unit 36 ​​are loaded with cultured cells. A certain pressing force is provided at the thoracic structure according to the experimental purpose.

[0161] 2) Set the relevant parameters of the simulated breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to the experimental needs, start the main breathing switch to make the aerosol exposure system start breathing movement.

[0162] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0163] Example 3 of the aerosol exposure system of the present invention:

[0164] The difference between this embodiment and embodiment 2 is that, in this embodiment, Figure 3 As shown, the piston push-pull device is outside the chest structure 43 and is connected to the chest structure 43. The piston push-pull device constitutes a breathing power device. In other embodiments, the breathing power device can be a vacuum generator integrated device of the prior art.

[0165] In the parameter setting of the piston push-pull device, the reset state is that the piston is at the outlet end of the piston cylinder 13 and the bionic lung unit is in a contracted recovery state. According to the set inhalation mode (mouth inhalation, nasal inhalation, mouth + nasal inhalation, etc.), the eighth valve 27 upstream and downstream of the bionic nasal cavity 28, the second valve 18, the fifth valve 22, the sixth valve 24 upstream and downstream of the bionic oral cavity 30, and the valves at the connection between the bionic oral cavity, bionic nasal cavity and bionic throat are in a closed or open state according to the set inhalation mode, the third valve 19 and the lower mouth of the bionic lung unit are in a closed state, and the first valve 17 and the fourth valve 20 are in an open state.

[0166] When the piston is pulled for the first time, it simulates the inhalation process of the body. The electric unit 11 sets the start time and the inhalation time T 吸 , inspiratory volume V 吸 , the inhalation waveform, the gas in the chest structure 43 is sucked into the piston cylinder 13, when the gas volume reaches the set V 吸 When the gas storage process is completed, the first valve 17 and the fourth valve 20 are closed. In the above process, the air pressure in the chest structure 43 is continuously reduced as the air is continuously pumped out. Under the action of the pressure difference, the outside air passes through the valve set to be opened, the bionic oral cavity 30 and / or the bionic nasal cavity 28 to reach the bionic lung unit. At this time, the bionic lung unit is in an expanded state.

[0167] When the piston is pushed for the first time, it simulates the exhalation process of the body. The time interval from the end of the inhalation process to the beginning of the exhalation process is T 屏 , that is, the breath holding time. According to the set exhalation mode (mouth exhalation, nose exhalation, mouth + nose exhalation, etc.), the first exhalation start time (after T 屏 After), the first exhalation time T 呼 , the third valve 19 is in a closed state, the first valve 17, the fourth valve 20 and the lower mouth of the bionic lung unit are in an open state, the eighth valve 27 upstream and downstream of the bionic nasal cavity 28, the second valve 18 upstream and downstream of the bionic oral cavity 30, the fifth valve 22, the seventh valve 25 and the valves at the connection between the bionic oral cavity, the bionic nasal cavity and the bionic throat are in a closed or open state according to the set exhalation mode, and control the gas volume passing through each within the exhalation time. The electric unit 11 is set according to the first exhalation start time and the first exhalation time T 呼 , expiratory volume V 呼 , exhalation waveform, the gas is pushed into the chest structure 43 by the piston cylinder 13. In the above process, the air pressure in the chest structure 43 is continuously increased as the air is pushed. Under the action of the pressure difference, the gas in the bionic lung unit is discharged into the atmosphere or the exhaust collector 26 through the bionic oral cavity 30 and / or the bionic nasal cavity 28 through the valve set to be opened.

[0168] When the set exhaled volume is greater than the previous inhaled volume, during the breath-holding time, the first valve 17 and the third valve 19 are opened, and the fourth valve 20 is closed. Pull the piston cylinder 13 to add gas into the piston cylinder 13. When the gas volume reaches the setting, the first valve 17 and the third valve 19 are closed. When the set exhaled volume is less than the previous inhaled volume, during the breath-holding time, the first valve 17 and the third valve 19 are opened, and the fourth valve 20 is closed. Push the piston cylinder 13 to reduce the gas volume in the piston cylinder 13. When the gas volume reaches the setting, the first valve 17 and the third valve 19 are closed.

[0169] During the exhalation process, the carbon dioxide supply device 38 supplies gas to the shunt container 41 according to the first exhalation start time, the first exhalation time, the exhaled carbon dioxide concentration, the exhaled carbon dioxide volume, and the exhalation waveform; at this time, the solenoid valve of the shunt container 41 is in a corresponding open state according to the first exhalation start time, the first exhalation time, and the gas volume distribution ratio in each direction, so as to control the gas volume passing through each during the exhalation time; the lower port of the bionic lung unit is in an open state, and the gas supplied by the carbon dioxide supply device 38 reaches the bionic lung unit through the shunt container 41 and the ventilation device 37, and then reaches the piston cylinder 13 together with the gas in the bionic lung unit, completing the process of exhaling carbon dioxide.

[0170] The time interval from the end of the first exhalation to the beginning of the second inhalation is the breathing interval T. 间隔 In T 间隔 After that, the next breathing process can be carried out according to the settings.

[0171] The entire mechanical ventilation process simulates the human breathing process and takes a total of T 吸 , breath holding time T 屏 , exhalation time T 呼 , breathing interval T 间隔 During the above time course, according to the experimental needs, pause time and corresponding inhalation and exhalation volumes were set in each time period to simulate special situations such as multiple small inhalations and multiple small exhalations of the human body.

[0172] In addition, the inhalation and exhalation process of the extrapulmonary culture unit 36 ​​connected here is as follows: the gas layer of the extrapulmonary culture unit 36 ​​has no expansion and contraction effect. In order to maintain the air pressure balance inside the extrapulmonary culture unit 36 ​​and reduce the damage to cells caused by the change of air pressure during inhalation and exhalation, the inhalation and exhalation process is completed by the following contents. The first lung unit 34 is connected to the upper part of the extrapulmonary culture unit 36. According to the above-mentioned breathing process, before the end of inhalation, the air inlet direction of the extrapulmonary culture unit 36 ​​connected to the first lung unit 34 is always in a closed state, and the side pipe 35 is in a closed state; after the end of inhalation, the air inlet direction connected to the first lung unit 34 is always in an open state, and at the beginning of exhalation, the upper port of the first lung unit 34 is in a closed state, and the side pipe is in an open state. Under the action of exhalation power, the gas in the first lung unit 34 and the gas in the extrapulmonary culture unit 36 ​​enter the bionic tracheobronchial tree 33 through the side pipe 35, and then are discharged from the bionic tracheobronchial tree 33.

[0173] Using the aerosol exposure system of the present invention to investigate the damage to lung cells in the chest-like breathing mode

[0174] 1) Set up the aerosol exposure system according to Figure 3 The second lung unit 40 and the extra-lung culture unit 36 ​​are connected in a manner to simulate chest breathing. The device is ensured to be sterile. The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells.

[0175] 2) Set the relevant parameters for simulating the body's thoracic breathing process on the computer to 1 breathing cycle. After setting N breathing cycles according to experimental needs, start the main ventilation switch to start the aerosol exposure system to perform breathing movements.

[0176] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0177] When the inspiratory and expiratory volumes of the chest-simulating breathing mode are set to a large value, it is used to simulate the damage to lung cells caused by chest compression.

[0178] Using the aerosol exposure system of the present invention to investigate the damage of oral and nasal mechanical ventilation to lung cells

[0179] 1) Set up the aerosol exposure system according to Figure 3 The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells. The ventilator is connected at the mouth or nose according to the breathing mode, and the ventilator parameters are set to simulate mechanical ventilation.

[0180] 2) Set the relevant parameters of the breathing process when the chest cavity expands and contracts as one chest breathing cycle on the computer. After setting N breathing cycles according to the experimental needs, start the ventilation master switch to start the breathing movement of the aerosol exposure system. Among them, the breathing trigger of the commercial ventilator has pressure trigger and time trigger. The pressure trigger performs ventilation according to the pressure change in the set negative pressure breathing process, and the time trigger determines whether the frequency rhythm is consistent with the negative pressure breathing process according to the time needs.

[0181] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0182] Using the aerosol exposure system of the present invention to investigate the damage of tracheal intubation ventilation to lung cells

[0183] 1) Set up the aerosol exposure system according to Figure 3 The apparatus is connected in a manner to simulate chest breathing. The apparatus is ensured to be sterile. The second lung unit 40 and the extrapulmonary culture unit 36 ​​are loaded with cultured cells. According to the experimental purpose, a tracheal tube is inserted into the throat end of the tracheal tree, and a ventilator is connected to the air supply end of the tracheal tube, and the ventilator parameters are set to simulate tracheal intubation ventilation.

[0184] 2) Set the relevant parameters of the breathing process when the chest cavity expands and contracts as one chest breathing cycle on the computer. After setting N breathing cycles according to the experimental needs, start the ventilation master switch to start the breathing movement of the aerosol exposure system. Among them, the breathing trigger of the commercial ventilator has pressure trigger and time trigger. The pressure trigger performs ventilation according to the pressure change in the set negative pressure breathing process, and the time trigger determines whether the frequency rhythm is consistent with the negative pressure breathing process according to the time needs.

[0185] 3) After N respiratory cycles, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0186] Using the aerosol exposure system of the present invention to investigate the damage of the target test substance to lung cells in the chest-like breathing mode

[0187] 1) When investigating the damage of target aerosols such as PM2.5, hazardous gases, drug aerosols, tobacco smoke, etc. in the environment to lung cells during mechanical ventilation, the generating device of PM2.5, hazardous gases, drug aerosols, tobacco smoke, etc. is used as the test substance source 23, and the opening frequency and opening ratio of the fifth valve 22 and the sixth valve 24 are adjusted according to the inhalation frequency and inhalation ratio of the target test substance, that is, the volume of the target test substance allowed to enter.

[0188] 2) Then the aerosol exposure system is as follows Figure 3 The second lung unit 40 and the extra-lung culture unit 36 ​​are connected in a manner to simulate chest breathing. The device is ensured to be sterile. The second lung unit 40 and the extra-lung culture unit 36 ​​are loaded with cultured cells.

[0189] 3) Set the relevant parameters for simulating the body's chest breathing process to 1 breathing cycle on the computer, and set the frequency, volume, and interval between inhaled target gas and breathing each time. After setting N breathing cycles and M inhaled target gases according to experimental needs, start the mechanical ventilation master switch to start breathing and inhalation movements of the mechanical ventilation aerosol exposure system.

[0190] 4) After N respiratory cycles and M inhalations of the target gas, the second lung unit 40 and the extrapulmonary culture unit 36 ​​are removed, and the cultured cells and supernatant loaded in the second lung unit 40 and the extrapulmonary culture unit 36 ​​are collected and analyzed using relevant cell damage analysis methods.

[0191] Using the aerosol exposure system of the present invention to investigate the damage to oral / nasal cells in the chest-like breathing mode

[0192] 1) Set up the aerosol exposure system according to Figure 3 The nasal cavity culture unit 29 and the oral cavity culture unit 31 are connected in a manner to simulate chest breathing. The device is ensured to be sterile. The nasal cavity culture unit 29 and the oral cavity culture unit 31 are loaded with cultured cells.

[0193] 2) Set the relevant parameters of the breathing process simulating chest expansion and contraction on the computer as one breathing cycle. After setting N breathing cycles according to experimental needs, start the main ventilation switch to start the breathing movement of the aerosol exposure system.

[0194] 3) After N respiratory cycles, the nasal culture unit 29 and the oral culture unit 31 are removed, and the cultured cells and supernatant loaded in the nasal culture unit 29 and the oral culture unit 31 are collected and analyzed using relevant cell damage analysis methods.

[0195] The aerosol exposure system of the present invention is used to investigate the effects of the chest-like breathing mode on the pressure, humidity, oxygen concentration, and carbon dioxide concentration in the mouth and respiratory system.

[0196] 1) Set up the aerosol exposure system according to Figure 3 Connect the monitoring unit (pressure, humidity, oxygen concentration, carbon dioxide concentration) at the location to be examined in the mouth and respiratory system.

[0197] 2) Set the relevant parameters of the breathing process simulating chest expansion and contraction on the computer as one breathing cycle. After setting N breathing cycles according to experimental needs, start the main ventilation switch to start the breathing movement of the aerosol exposure system.

[0198] 3) After N breathing cycles, the computer records and analyzes the time variation trend of pressure, humidity, oxygen concentration and carbon dioxide concentration at the target position during the breathing cycle.

[0199] Usually, when examining such indicators, the following methods can be used according to the target position to be examined: 1) connect a branch pipeline and connect a monitoring unit to the branch pipeline; 2) drill a hole in the bionic structure at the target position to be examined, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole; 3) when reconstructing the 3D graphics of the bionic structure, reserve a hole for the monitoring unit insertion position according to the target position to be examined, and then perform 3D printing, and paste a sealing ring around the inner circumference of the hole to ensure that the monitoring unit probe is in a sealed state after being inserted through the hole.

[0200] Example 4 of the aerosol exposure system of the present invention:

[0201] The difference between this embodiment and embodiment 1 is that in embodiment 1, two air inlet branches are provided, one of which is used to connect to the air source, and the other of which is used to connect to the test substance source. In this embodiment, one air inlet branch is provided, and the air inlet branch is connected to the air source or the test substance source.

[0202] Example 5 of the aerosol exposure system of the present invention:

[0203] The difference between this embodiment and embodiment 1 is that in embodiment 1, the carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline. In this embodiment, no shunt container is provided, and the carbon dioxide supply device is connected to the downstream of each bionic lung unit through a cross-connection through a carbon dioxide pipeline.

[0204] In addition, Embodiment 1, Embodiment 2 and Embodiment 3 of the present invention may be combined according to the purpose of use.

[0205] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. The patent protection scope of the present invention shall be based on the claims. All equivalent structural changes made using the contents of the description and drawings of the present invention should also be included in the protection scope of the present invention.

Claims

1. An aerosol exposure system, characterized in that The invention comprises a bionic oral cavity and a bionic nasal cavity arranged in parallel, wherein a bionic tracheobronchial tree is connected downstream of the bionic oral cavity and the bionic nasal cavity, and a bionic lung unit is connected downstream of the bionic tracheobronchial tree; the bionic oral cavity and the bionic nasal cavity are connected upstream to the same inlet and outlet pipeline, or the bionic oral cavity and the bionic nasal cavity are respectively connected upstream to different inlet and outlet pipelines; the pipelines where the bionic oral cavity and the bionic nasal cavity are located are respectively provided with a second valve and an eighth valve, and the inlet and outlet pipelines are connected to a breathing power device with four working stages In the first working stage, the respiratory power device is used to inhale gas from the air inlet and outlet pipes; in the second working stage, the respiratory power device is used to discharge the inhaled gas, so that the gas passes through the bionic oral cavity and / or bionic nasal cavity, and the bionic tracheal-bronchial tree in sequence and enters the bionic lung unit; in the third working stage, the respiratory power device is used to inhale the gas in the bionic lung unit through the bionic tracheal-bronchial tree, the bionic oral cavity and / or the bionic nasal cavity; in the fourth working stage, the respiratory power device is used to discharge the inhaled gas through the air inlet and outlet pipes.

2. The aerosol exposure system according to claim 1, characterized in that: A carbon dioxide supply device is connected to the downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the third working stage.

3. The aerosol exposure system according to claim 2, characterized in that: At least two bionic lung units are provided, and the aerosol exposure system comprises a shunt container, a carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

4. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: An intake branch pipe and an exhaust branch pipe are connected to the upstream of the air inlet and outlet pipelines. Two intake branches are provided, one of which is used to connect to a gas source containing clean gas, the other of which is used to connect to a test substance source containing aerosol, and the exhaust branch pipe is used to connect to an exhaust gas collector.

5. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: The inlet and outlet air pipelines are connected with a humidifying unit.

6. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: The bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

7. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: The breathing power device is a piston push-pull device.

8. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: The aerosol exposure system further comprises a bionic throat arranged at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

9. The aerosol exposure system according to claim 1, 2 or 3, characterized in that: At least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

10. An aerosol exposure system, characterized in that The invention comprises a bionic oral cavity and a bionic nasal cavity arranged in parallel, wherein the upstream of the bionic oral cavity and the bionic nasal cavity are connected to the same air inlet and outlet pipeline, or the upstream of the bionic oral cavity and the bionic nasal cavity are respectively connected to different air inlet and outlet pipelines; a second valve and an eighth valve are respectively arranged on the pipelines where the bionic oral cavity and the bionic nasal cavity are located, a bionic tracheobronchial tree is connected to the downstream of the bionic tracheobronchial tree, and a bionic lung unit is connected to the downstream of the bionic tracheobronchial tree; a breathing power device with four working stages is connected to the upstream of the bionic tracheobronchial tree, wherein in the first working stage, the breathing power device is used to inhale gas from the bionic oral cavity and / or the bionic nasal cavity; in the second working stage, the breathing power device is used to discharge the inhaled gas, and then the gas enters the bionic lung unit through the bionic tracheobronchial tree; in the third working stage, the breathing power device is used to inhale the gas in the bionic lung unit through the bionic tracheobronchial tree; in the fourth working stage, the breathing power device is used to discharge the inhaled gas through the bionic oral cavity and / or the bionic nasal cavity.

11. The aerosol exposure system according to claim 10, characterized in that: A carbon dioxide supply device is connected to the downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the third working stage.

12. The aerosol exposure system according to claim 11, characterized in that At least two bionic lung units are provided, and the aerosol exposure system comprises a shunt container, a carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

13. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: An intake branch pipe and an exhaust branch pipe are connected to the upstream of the inlet and outlet pipelines. Two intake branches are provided, one of which is used to connect to a gas source containing clean gas, and the other of the two intake branches is used to connect to a test substance source containing aerosol. The exhaust branch pipe is used to connect to an exhaust gas collector.

14. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: An inlet and outlet air pipeline is connected to the upstream of the bionic oral cavity and / or the bionic nasal cavity, and a humidification unit is connected to the inlet and outlet air pipeline.

15. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: The bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

16. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: The breathing power device is a piston push-pull device.

17. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: The aerosol exposure system further comprises a bionic throat arranged at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

18. The aerosol exposure system according to claim 10, 11 or 12, characterized in that: At least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

19. An aerosol exposure system, characterized in that The bionic oral cavity and bionic nasal cavity are arranged in parallel, the upstream of the bionic oral cavity and the bionic nasal cavity are connected to the same air inlet and outlet pipeline, or the upstream of the bionic oral cavity and the bionic nasal cavity are respectively connected to different air inlet and outlet pipelines; the pipelines where the bionic oral cavity and the bionic nasal cavity are located are respectively provided with a second valve and an eighth valve, the downstream of the bionic oral cavity and the bionic nasal cavity are connected to a bionic trachea-bronchial tree, and the downstream of the bionic trachea-bronchial tree is connected to a bionic lung unit; the aerosol exposure system also includes a thoracic structure, and the bionic lung units are all located in the thoracic structure; the thoracic structure The outside of the bionic lung unit is connected to a respiratory power device with two working stages. In the first working stage, the respiratory power device is used to extract gas in the chest cavity structure to reduce the air pressure in the chest cavity structure so that the gas enters the bionic lung unit through the bionic nasal cavity and / or bionic oral cavity, bionic throat, and bionic tracheal-bronchial tree; in the second working stage, the respiratory power device is used to inject gas into the chest cavity structure to increase the air pressure in the chest cavity structure so that the gas in the bionic lung unit is discharged through the bionic tracheal-bronchial tree, bionic throat, bionic nasal cavity, and / or bionic oral cavity.

20. The aerosol exposure system according to claim 19, characterized in that A carbon dioxide supply device is connected to the downstream of the bionic lung unit, and the carbon dioxide supply device is used to provide carbon dioxide to the bionic lung unit in the second working stage.

21. The aerosol exposure system according to claim 20, characterized in that At least two bionic lung units are provided, and the aerosol exposure system comprises a shunt container, a carbon dioxide supply device is connected to the shunt container, and the shunt container is connected to the downstream of each bionic lung unit through a carbon dioxide pipeline.

22. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: An intake branch pipe and an exhaust branch pipe are connected to the upstream of the inlet and outlet pipelines. Two intake branches are provided, one of which is used to connect to a gas source containing clean gas, and the other of the two intake branches is used to connect to a test substance source containing aerosol. The exhaust branch pipe is used to connect to an exhaust gas collector.

23. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: An inlet and outlet air pipeline is connected to the upstream of the bionic oral cavity and / or the bionic nasal cavity, and a humidification unit is connected to the inlet and outlet air pipeline.

24. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: The bionic tracheobronchial tree comprises multiple levels of bronchi, each level of the bronchi is connected to the bionic lung unit, at least one bionic lung unit is provided with a placement structure for placing a culture unit, at least one bionic lung unit is connected to a culture unit downstream and the culture unit is connected to the corresponding bronchus through a side pipeline.

25. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: The breathing power device is a piston push-pull device.

26. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: The aerosol exposure system further comprises a bionic throat arranged at the downstream intersection of the bionic oral cavity and the bionic nasal cavity.

27. The aerosol exposure system according to claim 19, 20 or 21, characterized in that: At least one of the bionic oral cavity, bionic nasal cavity, bionic tracheal-bronchial tree and bionic lung unit is provided with a placement structure for placing a culture unit.

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