Bionic cell extensometer connected with breathing machine

By designing a bionic cell stretcher, a hemispherical membrane of PDMS and PCL materials simulates respiratory movements of lung tissues and realizes three-dimensional stretching, solving the problem that traditional technology cannot simulate the in vivo mechanics microenvironment, reducing costs and in-depth research on the VILI mechanism.

CN120399879APending Publication Date: 2025-08-01刘奇
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Patent Information

Application Number
CN202510551964.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-04-29
Publication Date
2025-08-01

AI Technical Summary

Technical Problem

Traditional cell stretching technology cannot simulate the real mechanical microenvironment of cells in the body, especially three-dimensional stretching, and is costly, so it is impossible to conduct in-depth research on the lung injury mechanisms related to ventilators.

Method used

A bionic cell stretcher for ventilators is designed, including bionic bronchus and bionic thoracic silhouette. A hemispherical membrane made of PDMS and PCL materials simulates the respiratory movement of lung tissues, realizes multi-directional three-dimensional stretching, and simulates the real respiratory environment in the body through the collaborative work of multiple components.

Benefits of technology

It provides a mechanical microenvironment closer to physiological state, reduces experimental costs, can comprehensively simulate the mechanical stress changes of cells in the body, and conducts in-depth research on the mechanism of VILI generation.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to the field of cell stretching experiment equipment, in particular to a bionic cell stretching instrument for connecting a breathing machine, which comprises a bionic bronchial tube and a bionic thorax which are mutually sealed and movably connected, the bionic bronchial tube is an inverted cylindrical air chamber, the upper part of the bionic bronchial tube is closed, the lower part of the bionic bronchial tube is open, and the side wall of the bionic bronchial tube is provided with a breathing machine interface; the connector is connected with a respirator; the bionic thorax is similar to the bionic bronchus in shape and is also a cylindrical air chamber, the lower bottom of the bionic thorax is closed, the upper part of the bionic thorax is open, and an air outlet communicated with an internal cavity is formed in the side wall and extends outwards; a breathing unit is arranged between the bionic thorax shape and the bionic bronchus, the bionic bronchus is connected with an opening in the upper portion of the bionic thorax in a sealed mode, when the bionic dirty layer pleura swells downwards under the action of gas pressure, cells can be stretched in multiple directions, the limitation that in the prior art, the stretching direction is single is broken through, and the stretching effect is good. The three-dimensional stretching of the cells is realized, and the change of mechanical stress borne by the cells in vivo is more comprehensively simulated.
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Description

Technical Field

[0001] The invention relates to the field of cell stretching experimental equipment, in particular to a bionic cell stretching instrument for connecting to a ventilator. Background Art

[0002] Cells experience a variety of mechanical microenvironments under physiological conditions. In the normal human respiratory system, lung tissue cells are constantly subjected to mechanical forces, and mechanical stimulation plays a crucial regulatory role in cellular signal transduction. Mechanical ventilation is an essential respiratory support method for the treatment of various critically ill patients. Positive-pressure mechanical ventilation is a commonly used method. Unlike normal physiological breathing, where spontaneous inhalation inhales air under negative pressure, mechanical ventilation pushes air into the lung tissue under positive pressure. As a result, alveolar epithelial cells are subjected to the pull of positive-pressure gas throughout the respiratory process. This can easily induce ventilator-induced lung injury (VILI). The use of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) due to various causes is particularly prone to VILI, contributing to the high mortality rate among ARDS patients.

[0003] Lung strain is the ratio of the change in lung volume during breathing to the lung volume at rest (ΔV / V). Respiratory mechanics research aims to reveal the relationship between gas flow and the mechanical properties of lung tissue during breathing, while research at the cellular level provides a key entry point for explaining this complex physiological process from a microscopic perspective. Traditional cell research methods are mostly limited to static culture environments and cannot simulate the real mechanical microenvironment of cells in the body. Under static culture conditions, cells cannot receive physiologically relevant stretching stimuli, which makes the research results differ greatly from the actual situation in the body, making it difficult to accurately reveal the pathogenesis and cell biological behavior of diseases related to respiratory mechanics. Therefore, there is an urgent need for an experimental device that can accurately simulate the mechanical microenvironment of cells in vivo in vitro to meet the growing needs of scientific research.

[0004] Among the existing technical solutions for cell stretching, Flexcell's FX-5000Ttl cell stretching stress loading system is a representative example. It uses a rubber sealing gasket to generate negative pressure to deform the elastic basement membrane, which is achieved by pulling the elastic basement. The basement surface is coated with extracellular matrix to promote cell adhesion. This technical solution is a two-dimensional planar stretching and cannot perform three-dimensional stretching. In addition, the equipment is relatively expensive.

[0005] Traditional cell research methods cannot simulate the in vivo mechanical microenvironment, and there is an urgent need for experimental equipment that can accurately simulate the in vivo mechanical microenvironment of cells. The present invention provides a bionic cell stretching instrument for connecting to a ventilator. Summary of the Invention

[0006] Cells are regulated by the mechanical microenvironment under physiological conditions. Ventilator-induced lung injury (VILI) is prone to occur during mechanical ventilation, and the mechanism of VILI is not fully understood. Simulating the scenario of mechanical stress in vitro cell experiments is the key. Traditional cell research methods cannot simulate the in vivo mechanical microenvironment, and there is an urgent need for experimental equipment that can accurately simulate the in vivo mechanical microenvironment of cells. Existing cell stretching technology has high equipment costs and can only achieve two-dimensional stretching, unable to truly simulate the mechanical microenvironment during the breathing process. Therefore, a bionic cell stretching device connected to a ventilator is needed to simulate the mechanical microenvironment of cells under physiological conditions, deeply explore the mechanism of VILI, and reduce the cost of cell stretching experiments. The present invention can provide a mechanical microenvironment closer to the physiological state for cell research, contribute to the in-depth study of the mechanism of VILI, and can be applied to fields such as cell mechanics research, tissue engineering, and drug screening.

[0007] To achieve the above object, the technical solution of the present invention is as follows:

[0008] A bionic cell stretcher connected to a ventilator, comprising a bionic bronchus and a bionic thoracic cage that are hermetically and movably connected to each other. Among them, the bionic bronchus has a structure of an inverted cylindrical air chamber, which is closed at the top and open at the bottom, and a ventilator interface is provided on its side wall for connecting to a ventilator; the bionic thoracic cage has a shape similar to that of the bionic bronchus, also a cylindrical air chamber, which is closed at the bottom and open at the top, and there is an air outlet communicating with the internal cavity on the side wall and extending outward; a breathing unit is provided between the bionic thoracic cage and the bionic bronchus. The breathing unit includes a bionic visceral pleura and a bionic parietal pleura that are attached together. Both the bionic visceral pleura and the bionic parietal pleura are made of elastic materials; both the bionic visceral pleura and the bionic parietal pleura are hemispherical membranes. The bionic visceral pleura is above the bionic parietal pleura, and a gelatin layer for cell adhesion and growth is attached to the upper surface of the bionic visceral pleura to ensure airtightness during ventilation. After being subjected to gas pressure, it can be stretched downward, and the cells adhered to the gelatin layer can deform with the bionic visceral pleura.

[0009] The bionic bronchus realizes connection and ventilation with the ventilator. The bionic visceral pleura and the bionic parietal pleura of the breathing unit can deform during positive pressure ventilation and have elastic retraction ability, accurately simulating the breathing movement of lung tissue. The bionic thoracic cage provides stable support and connection. This design of multi-component collaborative work effectively simulates the real breathing environment in vivo, provides a mechanical microenvironment closer to the physiological state for cell research. At the same time, through the breathing unit composed of two hemispherical membranes, during the process of simulating the breathing movement, the device can stretch cells in multiple directions, breaking through the limitation of the single stretching direction in the prior art, realizing three-dimensional stretching of cells, and more comprehensively simulating the mechanical stress changes borne by cells in vivo.

[0010] Furthermore, the material of the bionic visceral pleura is polydimethylsiloxane (PDMS), and the bionic parietal pleura material is polycaprolactone (PCL). Among them, PDMS has low toxicity and immunogenicity to the cells and tissues of organisms, and is not likely to cause immune reactions and inflammatory reactions, which enables it to interact well with biological systems in the biomedical field; PDMS has good optical transparency, which is convenient for observation and research under instruments such as optical microscopes, and has a certain degree of ductility, which is convenient for stretching; PDMS is easy to process, and parameters such as the thickness, pore size, and surface morphology of the bionic membrane can be precisely controlled to meet the requirements of different application scenarios. PCL has good biocompatibility and can be used to construct a bionic environment; PCL is a relatively low-cost biodegradable polymer material, which has certain economic advantages in practical applications; PCL has good flexibility and a certain degree of strength, and can simulate the mechanical properties of biological membranes to a certain extent.

[0011] Furthermore, the area and curvature of the bionic visceral pleura are smaller than those of the bionic parietal pleura, and there is a certain space between the two membranes. In order to mimic the real structure of lung cell respiration, simulated pleural fluid can be added to the space to play a lubricating role.

[0012] Furthermore, a support ring one made of a flexible material is provided at the edge of the bionic visceral pleura, and a support ring two made of a flexible material is provided at the edge of the bionic parietal pleura. The support ring one and the support ring two are hermetically connected; the materials of the support ring one and the support ring two are silicone. A circular boss is provided in the middle of the inner wall of the bionic thoracic cage. A sealed tube portion extends downward from the bionic bronchus, and the sealed tube portion is hermetically connected to the opening above the bionic thoracic cage; after the support ring one and the support ring two are hermetically connected, the lower end surface of the support ring two is placed on the circular boss; the lower section of the sealed tube portion presses the upper end surface of the support ring one; an arc-shaped chute is provided on the inner wall of the opening above the bionic thoracic cage, and a connecting buckle protrusion is provided on the outer wall of the sealed tube portion; an arc-shaped chute extending along the circumferential direction of the inner wall is provided on the inner wall of the opening above the bionic thoracic cage, and the arc-shaped chute penetrates upward through the inner wall of the opening above the bionic thoracic cage to form a chute entrance. The connecting buckle protrusion enters the arc-shaped chute from the chute entrance. The radian of the arc-shaped chute is preferably 45 degrees, and the connecting buckle protrusion is locked in the arc-shaped chute by rotating the bionic bronchus.

[0013] Furthermore, a pleural fluid input tube is provided on the side surface of the support ring two on the bionic parietal pleura, and a pipeline groove is provided on the outer wall of the bionic thoracic cage for placing the pleural fluid input tube for rehydration at any time.

[0014] The beneficial points of the present invention are as follows:

[0015] 1. Effectively simulate the breathing movement. Traditional cell research is limited to static culture and cannot simulate the real mechanical microenvironment in the body. Through the coordinated work of multiple components such as the bionic bronchus, breathing unit, and bionic chest cage, it effectively simulates the real breathing environment in the body and provides a mechanical microenvironment closer to the physiological state for cell research.

[0016] 2. Achieve three-dimensional stretching. The sealed connection between the bionic bronchus and the upper opening of the bionic chest cage enables stretching of cells from multiple directions when the bionic visceral pleura bulges downward under gas pressure, breaking through the limitation of the single stretching direction in the existing technology and realizing three-dimensional stretching of cells, more comprehensively simulating the mechanical stress changes endured by cells in the body.

[0017] 3. High cost performance. Full consideration is given to cost factors. Through the optimization of the structure and the selection of appropriate materials, the production cost is greatly reduced on the premise of ensuring the maintenance of the experimental effect. Brief Description of the Drawings

[0018] Figure 1 is the structural assembly schematic diagram of the bionic cell stretcher for connecting to a ventilator of the present invention;

[0019] Figure 2 is the structural schematic diagram of the bionic bronchus in the present invention;

[0020] Figure 3 is the structural schematic diagram of the bionic visceral pleura in the present invention;

[0021] Figure 4 is the structural schematic diagram of the bionic parietal pleura in the present invention;

[0022] Figure 5 is the structural schematic diagram of the bionic bronchus in the present invention;

[0023] In the figure: 1. Bionic bronchus, 101. Ventilator interface, 102. Sealed tube part, 103. Connection buckle protrusion, 2. Bionic visceral pleura, 201. Support ring 1, 202. Gelatin layer, 3. Bionic parietal pleura, 301. Support ring 2, 302. Pleural fluid input tube, 4. Breathing unit, 5. Bionic chest cage, 501. Arc-shaped chute, 502. Air outlet, 503. Pipeline groove. Detailed Embodiments

[0024] The bionic cell stretcher for connecting to a ventilator of the present invention will be described in more detail below in conjunction with the drawings and through specific embodiments.

[0025] As Figure 1 - Figure 5 shown:

[0026] The present invention provides a bionic cell stretcher for connecting to a ventilator, which includes a bionic bronchus 1 and a bionic thoracic cage 5 that are hermetically and movably connected to each other. Among them, the bionic bronchus 1 has a structure of an inverted cylindrical air chamber, which is closed at the top and open at the bottom, and a ventilator interface is provided on its side wall for connecting to the ventilator; the bionic thoracic cage 5 has a similar shape to the bionic bronchus 1, also a cylindrical air chamber, which is closed at the bottom and open at the top, and there is an air outlet 502 communicating with the internal cavity on its side wall and extending outward; a breathing unit 4 is provided between the bionic thoracic cage 5 and the bionic bronchus 1. The breathing unit 4 includes a bionic visceral pleura 2 and a bionic parietal pleura 3 that are attached together. Both the bionic visceral pleura 2 and the bionic parietal pleura 3 are made of elastic materials. Among them, the bionic visceral pleura 2 is made of polydimethylsiloxane (PDMS), and the bionic parietal pleura 3 is made of polycaprolactone (PCL).

[0027] Both the bionic visceral pleura 2 and the bionic parietal pleura 3 are hemispherical membranes. The bionic visceral pleura 2 is above the bionic parietal pleura 3. A gelatin layer 202 for cell adhesion and growth is attached to the upper surface of the bionic visceral pleura 2 to ensure airtightness during ventilation. After being subjected to gas pressure, it can expand downward, and the cells adhered to the gelatin layer 202 can deform with the bionic visceral pleura 2. The area and curvature of the bionic visceral pleura 2 are smaller than those of the bionic parietal pleura 3, and there is a certain space between the two membranes. In order to mimic the real structure of lung cell respiration, a pleural fluid input tube 302 is provided on the side of the support ring two 301 on the bionic parietal pleura 3, and a pipeline groove 503 is provided on the outer wall of the bionic thoracic cage 5 for placing the pleural fluid input tube 302 to supplement the simulated pleural fluid at any time and play a lubricating role.

[0028] The bionic bronchus 1 realizes the connection and ventilation with the ventilator. The bionic visceral pleura 2 and the bionic parietal pleura 3 of the breathing unit 4 can deform during positive pressure ventilation and have elastic recoil ability, accurately simulating the breathing movement of lung tissue. The bionic chest cage 5 provides stable support and connection. This design of multi-component collaborative work effectively simulates the real breathing environment in the body, provides a mechanical microenvironment closer to the physiological state for cell research. At the same time, through the breathing unit 4 synthesized by two hemispherical membranes, during the process of simulating breathing movement, the device can stretch cells from multiple directions, breaking through the limitation of the single stretching direction in the prior art, realizing three-dimensional stretching of cells, and more comprehensively simulating the mechanical stress changes borne by cells in the body. A support ring one 201 made of flexible material is provided at the edge of the bionic visceral pleura 2, and a support ring two 301 made of flexible material is provided at the edge of the bionic parietal pleura 3. The support ring one 201 is hermetically connected to the support ring two 301; the materials of the support ring one 201 and the support ring two 301 are silicone. A circular boss is provided in the middle of the inner wall of the bionic chest cage 5. A sealed tube portion 102 extends downward from the bionic bronchus 1, and the sealed tube portion 102 is hermetically connected to the upper opening of the bionic chest cage 5; after the support ring one 201 is hermetically connected to the support ring two 301, the lower end surface of the support ring two 301 is placed on the circular boss; the lower section of the sealed tube portion 102 presses the upper end surface of the support ring one 201; an arc-shaped chute 501 is provided on the inner wall of the upper opening of the bionic chest cage 5, and a connecting buckle protrusion 103 is provided on the outer wall of the sealed tube portion 102; an arc-shaped chute 501 extending along the circumferential direction of the inner wall is provided on the inner wall of the upper opening of the bionic chest cage 5. The arc-shaped chute 501 penetrates upward through the inner wall of the upper opening of the bionic chest cage 5 to form a chute entrance. The connecting buckle protrusion 103 enters the arc-shaped chute 501 from the chute entrance. The radian of the arc-shaped chute 501 is preferably 45 degrees, and the connecting buckle protrusion 103 is locked in the arc-shaped chute 501 by rotating the bionic bronchus 1.

[0029] The experimental steps of the bionic cell stretcher for connecting with a ventilator of the present invention include:

[0030] S1: The bionic visceral pleura 2 is a PDMS membrane, and the membrane thickness is preferably 150 μm. A gelatin layer 202 is applied on the bionic visceral pleura 2 (PDMS membrane), and the thickness of the gelatin layer 202 is preferably 0.2 cm to attach (lung tissue) cells. S2: Adjust the density of the (lung tissue) cells attached to the gelatin layer 202 to be (1×10 5 / cm 2 ).

[0031] S3: Bond the bionic visceral pleura 2 to the bionic parietal pleura 3. After the first support ring 201 and the second support ring 301 are pressed together, place them into the bionic thoracic cage 5 together, with the first support ring 201 and the second support ring 301 placed on the annular protrusion; Insert the sealed tube portion 102 at the lower end of the bionic bronchus 1 above the bionic thoracic cage 5. The connecting buckle protrusion 103 enters the arc-shaped chute 501 from the chute entrance. The radian of the arc-shaped chute 501 is 45 degrees. Rotate the bionic bronchus 1 to lock the connecting buckle protrusion 103 in the arc-shaped chute 501, completing the sealing among the three components of the breathing unit 4, the bionic bronchus 1, and the bionic thoracic cage 5;

[0032] S4: Inject simulated pleural fluid through the pleural fluid input tube 302 provided on the side of the second support ring 301, with a volume of 1 ml;

[0033] S5: Connect the ventilator to the ventilator interface 101 in the present invention, turn on the ventilator, set the initial tidal volume to 3 ml, and ventilate continuously for 4 hours. Observe and record the initial data and subsequent data, including tidal volume, respiratory rate, airway pressure, and positive end-expiratory pressure.

[0034] After collecting the above data, simulate the respiratory mechanical properties of lung cells through modeling software. The occurrence of VILI depends on whether mechanical ventilation exceeds the physiological limit of the patient. See [Research progress on the application of respiratory mechanics-guided mechanical ventilation strategies in acute respiratory distress syndrome. Liu Qi, Cheng Zhe, Chen Rongchang; Chinese Journal of Tuberculosis and Respiratory Diseases 2015, 38(3): 208-211.]

[0035] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", etc. is the orientation or positional relationship based on the drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present invention.

[0036] In the above text, the exemplary embodiments of the present invention are described in detail with reference to the preferred embodiments. However, those skilled in the art can understand that without departing from the concept of the present invention, various modifications and variations can be made to the above specific embodiments, and various combinations can be made to the technical features and structures proposed by the present invention, without exceeding the protection scope of the present invention.

Claims

1. A bionic cell stretcher for connecting to a ventilator, characterized in that: It includes a bionic bronchus and a bionic chest cage that are hermetically and movably connected to each other. Among them, the bionic bronchus has a structure of an inverted cylindrical air chamber, which is closed at the top and open at the bottom. A ventilator interface is provided on its side wall for connecting to a ventilator; the bionic chest cage has a shape similar to that of the bionic bronchus, also a cylindrical air chamber, which is closed at the bottom and open at the top, and there is an air outlet communicating with the internal cavity on the side wall and extending outward; A breathing unit is provided between the bionic chest cage and the bionic bronchus. The breathing unit includes a bionic visceral pleura and a bionic parietal pleura that are attached together. Both the bionic visceral pleura and the bionic parietal pleura are made of elastic materials; Both the bionic visceral pleura and the bionic parietal pleura are hemispherical membranes. The bionic visceral pleura is above the bionic parietal pleura, and a gelatin layer for cell adhesion and growth is attached to the upper surface of the bionic visceral pleura.

2. The bionic cell stretcher for connecting a ventilator according to claim 1, wherein: The material of the bionic visceral pleura is polydimethylsiloxane, and the material of the bionic parietal pleura is polycaprolactone.

3. The bionic cell stretcher for connecting to a ventilator according to claim 1, characterized in that: The area and curvature of the bionic visceral pleura are smaller than those of the bionic parietal pleura, and there is a certain space between the two membranes.

4. The bionic cell stretcher for connecting a ventilator according to claim 1, wherein: A support ring one made of a flexible material is provided at the edge of the bionic visceral pleura, and a support ring two made of a flexible material is provided at the edge of the bionic parietal pleura. The support ring one and the support ring two are hermetically connected.

5. The bionic cell stretcher for connecting a ventilator according to claim 4, characterized in that: A circular boss is provided in the middle of the inner wall of the bionic chest cage. A sealed tube portion extends downward from the bionic bronchus, and the sealed tube portion is hermetically connected to the upper opening of the bionic chest cage; After the support ring one and the support ring two are hermetically connected, the lower end surface of the support ring two is placed on the circular boss; the lower end of the sealed tube portion presses the upper end surface of the support ring one; An arc-shaped chute is provided on the inner wall of the upper opening of the bionic chest cage, and a connecting buckle protrusion is provided on the outer wall of the sealed tube portion; An arc-shaped chute extending along the circumferential direction of the inner wall is provided on the inner wall of the upper opening of the bionic chest cage. The arc-shaped chute penetrates upward through the inner wall of the upper opening of the bionic chest cage to form a chute entrance. The connecting buckle protrusion enters the arc-shaped chute from the chute entrance, and the connecting buckle protrusion is locked in the arc-shaped chute by rotating the bionic bronchus.

6. The bionic cell stretcher for connecting a ventilator according to claim 4, wherein: A pleural fluid input tube is provided on the side surface of the support ring two on the bionic parietal pleura.

7. A bionic cell stretcher for connecting to a ventilator according to claim 4, characterized in that: The materials of the support ring one and the support ring two are silicone.