CN107271337B - Human alveolus aerosol deposition measurement experiment system - Google Patents
Human alveolus aerosol deposition measurement experiment system Download PDFInfo
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- CN107271337B CN107271337B CN201710271413.7A CN201710271413A CN107271337B CN 107271337 B CN107271337 B CN 107271337B CN 201710271413 A CN201710271413 A CN 201710271413A CN 107271337 B CN107271337 B CN 107271337B
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- 239000000443 aerosol Substances 0.000 title claims abstract description 33
- 230000008021 deposition Effects 0.000 title claims abstract description 30
- 238000002474 experimental method Methods 0.000 title claims abstract description 15
- 210000003456 pulmonary alveoli Anatomy 0.000 title claims description 9
- 238000005259 measurement Methods 0.000 title abstract description 12
- 239000002245 particle Substances 0.000 claims abstract description 61
- 210000004072 lung Anatomy 0.000 claims abstract description 37
- 230000000241 respiratory effect Effects 0.000 claims abstract description 26
- 239000000700 radioactive tracer Substances 0.000 claims abstract description 11
- 210000000621 bronchi Anatomy 0.000 claims description 23
- 238000007405 data analysis Methods 0.000 abstract description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 230000001575 pathological effect Effects 0.000 abstract description 2
- 210000002345 respiratory system Anatomy 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 238000005094 computer simulation Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000013618 particulate matter Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000000867 larynx Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000036391 respiratory frequency Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 238000001595 flow curve Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000005514 two-phase flow Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/04—Investigating sedimentation of particle suspensions
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- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
The invention discloses a human alveolar aerosol deposition measurement experiment system, wherein a standard particle generating device and an inhalation aerosol particle counter are respectively connected with a unidirectional air inlet valve through pipelines; the main pipeline of the unidirectional air inlet valve which is converged with the pipeline connected with the humidifier through the pipeline penetrates through the cover body of the transparent experimental container and is connected with the lung acinus experimental model arranged in the transparent experimental container, and the bottom of the transparent experimental container is connected with the simulated breathing pump through the pipeline; a pressure gauge is arranged on the transparent experiment container; the expired aerosol particle counter is connected with the one-way exhaust valve and the main pipeline in sequence through pipelines; the computer provided with the data analysis system is electrically connected with the PIV particle tracer and the simulated respiratory pump respectively, and the PIV particle tracer is arranged on one side of the transparent experimental container. The invention can provide in vitro measurements of the deposition rate of respirable particles in different particle sizes, respiratory patterns, ambient humidity and pathological conditions.
Description
Technical Field
The invention belongs to the technical fields of biomedical engineering, sanitary protection epidemic prevention technology and equipment, man-machine-environment system engineering, respiratory fluid mechanics, personal respiratory protection and the like, and particularly relates to a human alveolar aerosol deposition measurement experiment system.
Background
With the accelerated development of global industrialization, atmospheric pollution makes respiratory diseases a common and frequently occurring disease, and the deposition of inhalable particles (air-suspended particles with aerodynamic diameter of <10 μm) in the lung is one of the main causes. The human respiratory system consists of the respiratory tract (nose, pharynx, larynx, trachea, bronchi) and lungs. The main function of the respiratory tract is the passage of gases, which communicate the lungs with the environment. After the inhalable particles in the air enter the human body through the respiration, a part of the inhalable particles are deposited on the conduction part of the respiratory system of the human body, namely the nose, the pharynx, the larynx, the trachea, the main bronchus and the multi-stage bronchioles in the lung; the other part of the medicine enters the lung acinus area, a great amount of sediment causes lung lesions, influences respiratory function, and further penetrates through the alveolus wall to enter the blood circulation system of the human body, so that great harm is caused to the health of the human body.
On the other hand, with the deep knowledge of pulmonary function and diseases such as asthma, emphysema, chronic obstructive pulmonary disease, etc., it is recognized that inhalation administration is an effective way to treat the above diseases. The pulmonary inhalation preparation has the advantages of convenient use, quick response, avoidance of first pass effect of liver, reduction of adverse reactions possibly caused by systemic administration, excessive use of medicines and the like, and becomes a method for treating respiratory diseases which is widely focused at present. After the inhalation formulation enters the human body, most of the medicine deposited in the upper respiratory tract is discharged out of the body through the movement of cilia, and only the medicine deposited in the lung acinus can enter the blood circulation to be absorbed. I.e. to increase the bioavailability of inhaled drug delivery in the lungs, the amount of deposition in the acinar region of the lungs must be increased. Therefore, the in-vitro measurement experimental device for the pulmonary inhalable particulate deposition is established, and has great scientific research value and application value.
The upper respiratory tract particulate matter deposition can be measured and analyzed by a computer model and a CT scanning method for establishing a solid model. Patent CN 204797996U describes a method and apparatus for measuring the deposition of particles on the upper respiratory tract of a human body by a weighing method, which effectively solves the problem of analog measurement of the deposition of particles on the upper respiratory tract of a human body, but does not consider the humidifying effect of the upper respiratory tract on inhaled air and cannot measure the deposition of fine bronchi and alveoli of the human body.
The lung acinus is the main area of respiration, accounting for 90% of the volume of respiratory system, and it is necessary to measure the deposition of particulate matter lung acinus under various respiratory, environmental and disease effects and the like and find the deposition rule. The method for measuring the part mainly adopts the actual test method of experimental animals or volunteers at present, but has high cost, long experimental period and great side effect on human bodies. Because of the complicated structure and small size of the lung acinar region, a solid model cannot be established in a CT scanning mode. Chinese patent CN 104050321A describes a computer model of the running track of alveolar particles, which greatly simplifies the alveoli. However, the simulation result is based on the assumption of ideal boundary conditions, belongs to the category of computer simulation, the obtained data is not based on experimental results, and the obtained data usually needs to be further verified by a solid model, so that the practical application value is limited.
Chinese patent CN 102750859A adopts elastic silica gel material to prepare a device for simulating pulmonary ventilation, adjusts the elastic modulus of the silica gel material to be similar to that of human lungs, and realizes the simulation of elastic respiration. Although this patent provides a concept for establishing an elastic lung acinus model, it can only simulate the reproduction of the respiratory process and fails to conduct experiments of deposit of inhalable particles in the acinus area of the lung.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a human alveolar aerosol deposition measurement experiment system.
The technical scheme of the invention is summarized as follows:
the experimental system for measuring the aerosol deposition of the alveoli of the human body comprises a standard particle generating device 1-1 and an inhalation aerosol particle counter 1-2, wherein the standard particle generating device 1-1 and the inhalation aerosol particle counter 1-2 are respectively connected with a unidirectional air inlet valve 1-3 through pipelines; the one-way air inlet valve 1-3 penetrates through a cover body of the transparent experimental container 1-10 through a main pipeline 1-14 which is connected with a pipeline connected with the humidifier 1-4, is connected with a simulated 15-level bronchus 2-1 of a lung acinus experimental model 1-9 arranged in the transparent experimental container 1-10, the simulated 15-level bronchus 2-1 is connected with 2 simulated 16-level bronchus 2-3 through a first Y-shaped tee joint 2-2, each simulated 16-level bronchus 2-3 is connected with 2 simulated 17-level bronchus 2-5 through a second Y-shaped tee joint 2-4, each simulated 17-level bronchus 2-5 is connected with a simulated lung acinus cluster 2-7 through a connecting pipe 2-6, the simulated lung acinus cluster 2-7 comprises a simulated alveolus tube 3-4, an interface 3-1 is arranged on the simulated alveolus tube 3-4, an annular bulge 3-2 is arranged on the outer wall of the interface 3-1, and the simulated acinus 3-1 is movably connected with the interface 3-1 and is fixed through the annular bulge 3-2; the bottom of the transparent experimental container 1-10 is connected with the simulated respiratory pump 1-11 through a pipeline; the transparent experiment container 1-10 is provided with a pressure gauge 1-8; the expired aerosol particle counter 1-6 is connected with the unidirectional exhaust valve 1-5 and the main pipeline 1-14 in sequence through pipelines; the computer 1-12 provided with the data analysis system is respectively and electrically connected with the PIV particle tracer 1-13 and the simulated respiratory pump 1-11, and the PIV particle tracer 1-13 is arranged on one side of the transparent experimental container 1-10.
The invention has the advantages that:
the invention can provide in vitro measurements of the deposition rate of respirable particles in different particle sizes, respiratory patterns, ambient humidity and pathological conditions. The invention is hopeful for experimental staff to reveal the deposition rule and influencing factors of lung acinar region particles, explore the cause, development, prevention, targeted therapy and optimization of inhalable therapy of lung diseases, and is used for replacing experimental animals or volunteers to analyze the curative effect of medicaments and develop new medicaments.
Drawings
FIG. 1 is a schematic diagram of the present invention.
Fig. 2 is a schematic diagram of a lung acinus experimental model structure.
Fig. 3 is a schematic view of a simulated lung acinar tube and a simulated lung acinar partial cross-section.
Detailed Description
The invention will be further illustrated with reference to specific examples.
The standard particle generating apparatus of the present invention is commercially available, taking the F9531 standard particle generating apparatus as an example. But not limiting the invention.
Aerosol particle counters are commercially available.
The invention provides a measurement experiment device capable of measuring the deposition rate, the deposition distribution, the single alveolar deposition amount and the flow field distribution of a lung acinar region model of a human body, which is provided with a standard particle generating device, an aerosol particle counter, a simulated respiratory pump, a humidifier, a PIV particle tracer and the like.
The experimental system for measuring the aerosol deposition of the alveoli of the human body comprises a standard particle generating device 1-1 and an inhalation aerosol particle counter 1-2, wherein the standard particle generating device 1-1 and the inhalation aerosol particle counter 1-2 are respectively connected with a unidirectional air inlet valve 1-3 through pipelines; the one-way air inlet valve 1-3 penetrates through a cover body of the transparent experimental container 1-10 through a main pipeline 1-14 which is connected with a pipeline connected with the humidifier 1-4, is connected with a simulated 15-level bronchus 2-1 of a lung acinus experimental model 1-9 arranged in the transparent experimental container 1-10, the simulated 15-level bronchus 2-1 is connected with 2 simulated 16-level bronchus 2-3 through a first Y-shaped tee joint 2-2, each simulated 16-level bronchus 2-3 is connected with 2 simulated 17-level bronchus 2-5 through a second Y-shaped tee joint 2-4, each simulated 17-level bronchus 2-5 is connected with a simulated lung acinus cluster 2-7 through a connecting pipe 2-6, the simulated lung acinus cluster 2-7 comprises a simulated alveolus tube 3-4, an interface 3-1 is arranged on the simulated alveolus tube 3-4, an annular bulge 3-2 is arranged on the outer wall of the interface 3-1, and the simulated acinus 3-1 is movably connected with the interface 3-1 and is fixed through the annular bulge 3-2; the bottom of the transparent experimental container 1-10 is connected with the simulated respiratory pump 1-11 through a pipeline; the transparent experiment container 1-10 is provided with a pressure gauge 1-8; the expired aerosol particle counter 1-6 is connected with the unidirectional exhaust valve 1-5 and the main pipeline 1-14 in sequence through pipelines; the computer 1-12 provided with the data analysis system is electrically connected with the PIV particle tracer 1-13 and the simulated respiratory pump 1-11 respectively, and the PIV particle tracer 1-13 is arranged on one side of the transparent experimental container 1-10.
The simulated lung acinus can be natural latex with the elastic modulus and poisson ratio consistent with the biomechanical parameters of alveoli, for example: model CY50X2 is merely exemplary and is not intended to be limiting.
The simulated lung acinus and all levels of fine bronchi are movably connected, and can be disassembled into a single unit, so that the single analysis is convenient.
The standard particle generating device is a two-phase flow aerosol generator which can generate the concentration of more than 10 6 Individual/cm 3 The particle size range of the highly monodisperse aerosols is 0.1 μm to 8 μm, the particle size and concentration of the particles can be varied.
The simulated respiratory pump is piston type.
The invention relates to the use of a human alveolar aerosol deposition measurement experiment system, which comprises the following steps:
by using the experimental system for measuring the aerosol deposition of the human alveoli, the leakage is determined to be free by pressurization; opening a one-way air inlet valve 1-3, starting a standard particle generating device 1-1, generating monodisperse polystyrene microspheres, starting an inhalation aerosol particle counter 1-2, and measuring the generation concentration until the sampling concentration is stable; setting a simulated respiratory pump 1-11 to achieve the pressure and flow period required by the experiment, starting the simulated respiratory pump 1-11, and starting to record respiratory cycle; opening a one-way exhaust valve 1-5, opening an expired aerosol particle counter 1-6, measuring the expired aerosol concentration, and recording the accumulated time number; the ratio of the difference value of the inhalation concentration and the exhalation concentration to the inhalation concentration is the total particulate matter deposition rate of the lung acinus experimental model 1-9. When the system works, the humidifier 1-4 humidifies aerosol, and the pressure gauge 1-8 records pressure. After the experiment is started, starting the PIV particle tracer 1-13, and measuring the movement speed and flow field of inhalable particles in lung acinus; after the set respiratory cycle times are reached, the standard particle generating device 1-1, the inhalation aerosol particle counter 1-2, the simulated respiratory pump 1-11 and the one-way air inlet valve 1-3 are sequentially closed; and calculating the total deposition rate of the particles in the lung acinar region of the human body.
The simulated respiratory pump is controlled by a computer, so that the simulated respiratory frequency, tidal volume, residual volume, differential pressure and respiratory flow can be measured, and a respiratory flow curve can be drawn.
The humidifier can humidify 50-100% of the lung acinus experimental model.
The PIV particle tracer is used for displaying and calculating the movement speed and track of the particles in each region in the simulated lung acinar cluster.
The invention can simulate the biomechanics and respiratory characteristics of the real human lung acinus area and realize the measurement of the motion trail and the deposition rate of the inhalable particles outside the human lung acinus area.
The computer 1-12 and PIV particle tracer 1-13 with data analysis system can display the movement track of the particles in the system and measure the movement parameters in real time.
The one-way valve ensures that the aerosol movement is one-way.
The lid of transparent experimental container can be opened and closed, installs the tight structure and ensures that the experimental container is airtight when closing.
When the system is operated, the deposition condition of aerosols with different respiratory flow rates in a steady-state respiratory mode in a model can be obtained through measuring different respiratory frequencies and respiratory depths. By changing the aerosol properties, the inhalation treatment effect of the medicine and the distribution and diffusion condition of the medicine after entering alveoli can be simulated. Variations in inhalable particulate deposition under pulmonary lesion conditions can be made by varying the bronchial shape and alveolar shape, size, thickness, and modulus of elasticity.
Claims (1)
1. The experimental system for measuring the deposition of the human alveolus aerosol comprises a standard particle generating device (1-1) and an inhalation aerosol particle counter (1-2), and is characterized in that the standard particle generating device (1-1) and the inhalation aerosol particle counter (1-2) are respectively connected with a one-way air inlet valve (1-3) through pipelines; the one-way air inlet valve (1-3) penetrates through a cover body of the transparent experimental container (1-10) through a main pipeline (1-14) which is connected with a pipeline of the humidifier (1-4), is connected with a simulated 15-level bronchus (2-1) of a lung acinus experimental model (1-9) arranged in the transparent experimental container (1-10), the simulated 15-level bronchus (2-1) is connected with 2 simulated 16-level bronchus (2-3) through a first Y-shaped tee joint (2-2), each simulated 16-level bronchus (2-3) is connected with 2 simulated 17-level bronchus (2-5) through a second Y-shaped tee joint (2-4), each simulated 17-level bronchus (2-5) is connected with a simulated acinus cluster (2-7) through a connecting pipe (2-6), the simulated acinus cluster (2-7) comprises a simulated alveolus tube (3-4), an interface (3-1) is arranged on the simulated 15-level bronchus (2-1), a ring-shaped bulge (3-3) is arranged on the outer wall of the interface (3-1), and the ring-shaped bulge (3-3) is fixedly connected with the simulated acinus (3-3) through the ring-shaped bulge (3-3); the bottom of the transparent experiment container (1-10) is connected with the simulated respiratory pump (1-11) through a pipeline; a pressure gauge (1-8) is arranged on the transparent experiment container (1-10); the expiratory aerosol particle counter (1-6) is connected with the unidirectional exhaust valve (1-5) and the main pipeline (1-14) in sequence through pipelines; the PIV particle tracer (1-13) is arranged on one side of the transparent experimental container (1-10).
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| CN201710271413.7A CN107271337B (en) | 2017-04-24 | 2017-04-24 | Human alveolus aerosol deposition measurement experiment system |
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| AU2020260764B2 (en) * | 2019-04-24 | 2022-11-24 | Cipla Limited | Methods and systems for simulating deposition of inhaled drug on lungs |
| CN118506668A (en) * | 2019-09-18 | 2024-08-16 | 苏州新劢德医疗器械科技有限公司 | Novel human respiratory tract model |
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| CN111595739B (en) * | 2020-05-21 | 2021-08-10 | 中国矿业大学 | Human respiratory particulate matter deposition simulation and monitoring experiment system |
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| CN113465873B (en) * | 2021-05-20 | 2024-06-11 | 西安医学院第一附属医院 | Experimental device for simulating internal flow of respiratory tract |
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