CN111096255A - Non-operative intervention fish artificial lung system and application thereof - Google Patents

Non-operative intervention fish artificial lung system and application thereof Download PDF

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CN111096255A
CN111096255A CN201911402410.8A CN201911402410A CN111096255A CN 111096255 A CN111096255 A CN 111096255A CN 201911402410 A CN201911402410 A CN 201911402410A CN 111096255 A CN111096255 A CN 111096255A
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gas
sensor
exchange
membrane
artificial lung
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CN111096255B (en
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赵晓赟
彭茜
王子琦
王慧泉
陈冬艳
魏翼彤
张国新
冯雪
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TIANJIN CHEST HOSPITAL
Nankai University
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TIANJIN CHEST HOSPITAL
Nankai University
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K61/00Culture of aquatic animals
    • A01K61/10Culture of aquatic animals of fish
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K63/00Receptacles for live fish, e.g. aquaria; Terraria
    • A01K63/003Aquaria; Terraria
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K63/00Receptacles for live fish, e.g. aquaria; Terraria
    • A01K63/04Arrangements for treating water specially adapted to receptacles for live fish
    • A01K63/042Introducing gases into the water, e.g. aerators, air pumps
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K63/00Receptacles for live fish, e.g. aquaria; Terraria
    • A01K63/04Arrangements for treating water specially adapted to receptacles for live fish
    • A01K63/045Filters for aquaria
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01DMEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
    • G01D21/00Measuring or testing not otherwise provided for
    • G01D21/02Measuring two or more variables by means not covered by a single other subclass
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A40/00Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
    • Y02A40/80Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in fisheries management
    • Y02A40/81Aquaculture, e.g. of fish

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  • Life Sciences & Earth Sciences (AREA)
  • Environmental Sciences (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Farming Of Fish And Shellfish (AREA)

Abstract

The invention discloses a non-operative intervention fish artificial lung system, which comprises an adjustable culture solution O2Partial pressure, CO2Partial pressure, H+Concentration, HCO3 The membrane exchange system with any one or more of the parameters of the concentration can be used for establishing an animal model simulating the respiratory system of a human and the application in researching the respiratory diseases such as hypoxemia, hyperoxemia, hypocapnia, hypercapnia and the like of the human.

Description

Non-operative intervention fish artificial lung system and application thereof
Technical Field
The invention relates to the technical field of biology, in particular to a non-operative intervention fish artificial lung system and application thereof in model establishment for simulating human respiratory diseases.
Background
With the development of aging population, the aggravation of environmental pollution, the inundation of tobacco, the abuse of drugs and toxicants, the abuse of respiratory infectious diseases and the like, the incidence rate of respiratory system abnormality caused by respiratory system diseases and other related system diseases tends to rise year by year, the number of accumulated patients also increases rapidly, the proportion and the number of patients with chronic respiratory diseases are increased rapidly, the death rate of respiratory chronic diseases is the third place of the death rate of diseases in the world, and the medical burden and the social and economic burden are increasingly serious. For example: hypoxemia, hyperoxemia, hypocapnia, and hypercapnia.
Hypoxemia refers to the partial pressure of oxygen in the blood, arterial blood oxygen (PaO)2) Lower than the lower normal limit of the same age, mainly manifested as a decrease in blood oxygen partial pressure and blood oxygen saturation. Adult normal arterial partial oxygen pressure (PaO)2): 83-108 mmHg. Hypoxia may occur due to dysfunction of ventilation and/or air exchange caused by various causes such as central nervous system disorders, bronchial and pulmonary disorders, etc. The degree, speed and duration of hypoxemia are different, and the influence on the body is different. Hypoxemia is one of the common critical diseases of respiratory department and is also one of the important clinical manifestations of respiratory failure.
Hyperoxia refers to that when rescue or oxygen therapy is carried out, a large amount of oxygen enters venous blood through the alveolar wall, so that the oxygen concentration is greatly increased, and PaO is enabled2Obviously improved, the oxygen partial pressure is more than or equal to 120mmHg, which is a common phenomenon in clinic. The lethality of hyperoxia is higher than that of hypoxemia.
Hypocapnia, also known as respiratory alkalosis, refers to the hyperventilation of the lung causing plasma H2CO3Concentration or PaCO2Primary decrease, resulting in an increase in pH (>7.45). The disease is divided into acute and chronic types according to the disease condition. Acute patient PaCO2For every 10mmHg (1.3kPa) decrease, HCO3 The reduction is about 2 mmol/L; chronic person HCO3 The concentration is reduced to 4-5 mmol/L.
Hypercapnia is carbon dioxide (CO) in blood2) Abnormal rise in level. Hypercapnia typically triggers an enhanced respiratory and oxygen response, such as waking and turning the head while sleeping. If such a reaction is not performed, it may be fatal, as if the infant suddenly died.
Compared with clinical tests, the inducible animal model has the advantages of stronger controllability, intuition and easiness in repetition, and can be used for accurately researching the respiratory system diseases from multiple angles such as anatomical morphology, histopathology, gene and molecular biology and the like. Therefore, the search for a simple and stable animal model which is closer to the human pathogenesis is urgent.
The genome of fish, such as zebra fish, has 87 percent of coincidence with the human genome, has high homology, has prominent advantages as a model organism, and plays an important role in the research of human diseases by using a disease model copied by the zebra fish. Zebrafish, as a model animal, are favored by scientists in many research fields due to their unique advantages of embryo in vitro fertilization, in vitro development, transparent embryo body, easy observation, large reproductive capacity, fast growth rate, sufficient samples, etc. Internationally, the use of zebrafish-model organisms is gradually expanding and deepening into the research of development, functions and diseases of various systems (nervous system, immune system, cardiovascular system, reproductive system, etc.) of a living body, and has been applied to large-scale new drug screening of small-molecule compounds. The zebra fish is simple in microscopic operation and has mature gene overexpression and expression inhibition strategies. The development process of each organ and system is similar, and a plurality of mutants thereof are similar to the phenotype generated by human gene mutation. Therefore, the zebra fish can be used for establishing an animal model for gene function research, human disease genotype/phenotype research, drug screening and identification aiming at major disease treatment.
Because fish exchange gas by gills and do not have human respiratory systems, the application of the gills in the field of respiratory disease research is few, so that zebra fish cannot be widely used for respiratory disease research until now. If the O in the zebra fish culture solution can be changed2Partial pressure, CO2Partial pressure or H+Concentration, HCO3 The concentration of the extract can also change the O in the zebra fish body correspondingly2、CO2Partial pressure or H+、HCO3 Concentration, simulating achievement of high oxygen, oxygen deficit, high CO2Low CO content2And hypercapnia, etc. in human respiratory diseases. The method is equivalent to constructing an in-vitro artificial membrane lung for the zebra fish, so that various respiratory disease models can be constructed by utilizing the zebra fish and corresponding research can be carried out.
Therefore, the establishment of a device which can simulate human respiratory diseases by using zebra fish modeling has the characteristics of high intelligence, simple operation, convenient use, short-term grasp by non-professionals and the like, and is a problem to be solved by the technical personnel in the field. Of course, the device is not limited to the study of zebra fish, and other aquatic animals and plants can be raised in the specific environment provided by the system and related scientific research can be carried out if needed.
Disclosure of Invention
In order to overcome the technical defects, the invention aims to provide a method for changing O in zebra fish breeding liquid without changing the physiological anatomical structure of fish2Partial pressure, CO2Partial pressure, N2Partial pressure, H+Concentration and HCO3 Concentration, regulating pH value and gas concentration in the feed liquid for feeding zebra fish, accurately regulating the components of the feed liquid, maintaining the special stable environment of zebra fish, detecting, recording, and simulating to establish comprehensive pathophysiology of human under respiratory diseases such as hypoxemia, hyperoxemia, hypocapnia and hypercapniaStudy data; meanwhile, compared with clinical experiments, the induced animal model with stronger controllability, intuition and easy repeatability is used for researching the respiratory system diseases from multiple angles such as anatomical morphology, histopathology, gene and molecular biology, is simple and stable, is closer to the human morbidity characteristics, and is applied to simulating the human respiratory diseases.
In order to achieve the purpose, the invention is realized by the following technical scheme:
an artificial lung system of non-operative intervention fish comprises an adjustable culture solution O2Partial pressure, CO2Partial pressure, H+Concentration, HCO3 -Membrane exchange system of any one or several of the parameters of concentration.
The technical scheme is that the non-operative intervention fish artificial lung system comprises a control system, a membrane exchange system, a feeding tank and a plurality of air sources; the membrane exchange system comprises an exchange bin and an exchange membrane; the exchange membrane is arranged in an exchange bin of pre-mixed water; the gas sources are communicated with the gas inlet of the exchange membrane; the inside of the exchange membrane is provided with an air cavity, and the outside of the membrane is provided with premixed water; the feeding liquid in the exchange bin is communicated with the water inlets of the plurality of feeding cylinders through pipelines; a plurality of sensors and control valves are arranged on the plurality of gas sources; the control system is electrically connected with the various sensors and the control valve respectively.
Preferably, the water inlet of the exchange bin is respectively connected with an acid liquid source, an alkaline liquid source and a clean water source through pipelines; the acid liquid source, the alkaline liquid source and the clean water source are respectively provided with a plurality of sensors and control valves; the control system is electrically connected with various sensors and control valves on each unit respectively.
Preferably, a gas mixing bin is arranged on a connecting pipeline between the various gas sources and the gas inlet of the exchange membrane; the various gas sources are O2Gas source, CO2Gas source, N2One or more combinations of air sources, air and other air sources; sensors and control valves are arranged on the various gas sources; a sensor is arranged in the gas mixing bin; the control system is respectively connected with a plurality of air sources and airAll sensors on the body mixing bin are electrically connected with the control valve; and the gas outlet of the exchange membrane is communicated with the gas mixing bin through a one-way pipeline.
Preferably, the sensor includes one or a combination of more of a pressure sensor, a flow sensor, a gas partial pressure sensor, a ph sensor, a temperature sensor, a humidity sensor, a water level sensor, and a liquid component sensor.
Preferably, the feeding liquid in the exchange bin is respectively communicated with the water inlets of the plurality of feeding tanks through a circulating pump and a pipeline; the plurality of feeding cylinders are arranged in parallel; the control system is electrically connected with the circulating pump.
Preferably, the feeding cylinder comprises a sealing cover and a cylinder body; a liquid level sensor and a temperature sensor are arranged in the feeding cylinder; the control system is electrically connected with the liquid level sensor and the temperature sensor; the water outlet of the feeding cylinder is communicated with the filtering system through a pipeline; the filtering system comprises a sewage filter and a sewage disposal pool which are communicated in sequence; the clean water outlet of the sewage filter is communicated with the exchange bin through a pipeline; a liquid level sensor, a flow sensor and a flow control valve are respectively arranged on the sewage filter and the sewage disposal pool; the control system is electrically connected with the liquid level sensor, the flow sensor and the flow control valve.
Preferably, the fish is selected from zebrafish.
The invention relates to an artificial lung system of non-operative intervention fish, which is applied to the preparation of an animal model simulating a human respiratory system.
The invention relates to an artificial lung system of non-operative intervention fish, which is applied to the preparation of animal models simulating respiratory diseases in human hypoxemia, hyperoxia, hypocapnia and hypercapnia.
The invention has the beneficial effects that:
through the accurate control of a control system, the pH value and the solubility of each gas in the feeding liquid for feeding the zebra fish are adjusted, the accurate adjustment of material components is carried out, the specific steady-state environment of the zebra fish is maintained, the detection record is carried out, and the comprehensive pathophysiology research data of human beings under the respiratory diseases such as hypoxemia, hyperxemia, hypocapnia and hypercapnia are simulated and established.
Compared with clinical experiments, the induced animal model with stronger controllability, intuition and easy repeatability is used for researching the respiratory system diseases from multiple angles such as anatomical morphology, histopathology, gene and molecular biology more accurately, and the fish extracorporeal membrane exchange respiratory system is simple, stable and closer to the human morbidity characteristics.
The invention does not need surgical intervention, does not cause damage to experimental animals (fishes), does not cause emergency reaction, and ensures the stability and reproducibility of experimental results.
Drawings
The invention will now be described, by way of example, with reference to the accompanying drawings, in which:
figure 1 is a schematic diagram of the main structure of the present invention.
Fig. 2 is a schematic diagram of the connection of the control system with various sensors and control valves according to the present invention.
Fig. 3 is a schematic structural view of the gas mixing bin of the present invention.
FIG. 4 is a schematic diagram of the structure of the membrane exchange system of the present invention.
Fig. 5 is a schematic view of the structure of the feeding cylinder of the present invention.
FIG. 6 is a schematic diagram of the construction of the filtration system of the present invention.
Fig. 7 is a schematic diagram showing the overall operation of the system of the present invention.
The labels in the figure are: a control system 1, a gas mixing bin 2, a membrane exchange system 3, a feeding cylinder 4, a sewage filter 5 and O2Gas source 6, CO2Gas source 7, N2The device comprises a gas source 8, an acid liquid source 9, an alkaline liquid source 10, a clean water source 11, a sewage disposal pool 12 and a power supply 13.
Gas outlet 201, gas mixing bin housing 202, gas mixing bin sensor 203, O2Inlet 204, CO2Air inlet 205, N2An air inlet 206 and a mixed air inlet 207.
The device comprises a circulating pump 301, a membrane exchange system sensor 302, an exchange membrane air inlet 303, an exchange bin shell 304, a clean water inlet 305, an acid liquid source inlet 306, an alkaline liquid source inlet 307, an exchange membrane air outlet 308, an exchange bin 309, an exchange membrane 310 and an air cavity 311.
The device comprises a sealing cover 401, a feeding cylinder water inlet 402, a cylinder body 403, a feeding cylinder sensor 404 and a feeding cylinder water outlet 405.
A sewage filter sensor 501, a sewage drain opening 502, a sewage filter housing 503, and a clean water outlet 504.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1, as shown in FIG. 7, the present invention is a non-surgical intervention fish artificial lung system comprising an adjustable culture solution O2Partial pressure, CO2Partial pressure, H+Concentration, HCO3 -Membrane exchange system of any one or several of the parameters of concentration.
Embodiment 2, a non-surgical intervention artificial lung system for fish, comprising a control system 1, a membrane exchange system 3, a feeding tank 4 and a plurality of air sources; the membrane exchange system 3 comprises an exchange bin 309 and an exchange membrane 310; the exchange membrane 310 is placed in an exchange bin 309 of pre-mixed water; the various gas sources are communicated with the gas inlet of the exchange membrane 310; the inside of the exchange membrane 310 is provided with an air cavity, and the outside of the membrane is provided with premixed water; the feeding liquid in the exchange bin 309 is communicated with a plurality of feeding cylinder water inlets 402 through pipelines; a plurality of sensors and control valves are arranged on the plurality of gas sources; the control system 1 is electrically connected to various sensors and control valves, respectively.
The sensors comprise one or more combinations of a pressure sensor, a flow sensor, a gas partial pressure sensor, a pH value sensor, a temperature sensor, a humidity sensor, a water level sensor and a liquid component sensor, and each sensor acquires the running state information of a component and feeds the information back to the control system, and the control system makes a corresponding control instruction.
The control system 1 is a BreathFish software system. The control system 1 controls the introduction amount of each gas source in the multiple gas sources into the exchange membrane gas cavity 311 according to a set proportion, the gas is dispersed into the pre-mixed water in the exchange bin 309 through the exchange membrane 310 to form a feeding liquid, and the pre-mixed water in the exchange bin 309 cannot enter the exchange membrane gas cavity; the control system 1 controls the distribution of the feeding liquid to a plurality of feeding vats 4.
Example 3, as shown in fig. 1 and 4, the water inlets of the exchange chamber 309 are respectively connected with the acid liquid source 9, the alkaline liquid source 10 and the clean water source 11 through pipes; the acid liquid source 9, the alkaline liquid source 10 and the clean water source 11 are respectively provided with a plurality of sensors and control valves; the control system 1 is electrically connected with various sensors and control valves on each unit.
The membrane exchange system 3 comprises a circulating pump 301, a membrane exchange system sensor 302, an exchange membrane air inlet 303, an exchange bin shell 304, a clean water inlet 305, an acid liquid source inlet 306, an alkaline liquid source inlet 307, an exchange membrane air outlet 308, an exchange bin 309, an exchange membrane 310 and an air cavity 311.
The acid liquid source 9 enters the exchange bin 309 through the acid liquid source inlet 306; the alkaline liquid source 10 enters the exchange bin 309 through the alkaline liquid source inlet 307; and a pH value sensor, a liquid component sensor and a flow control valve which are electrically connected with the control system 1 are respectively arranged on the acid liquid source channel and the alkaline liquid source channel. The cleaning water source 11 is introduced into the exchange tank 309 through the cleaning water inlet 305, and a liquid component sensor and a flow control valve electrically connected to the control system 1 are installed on a path of the cleaning water source.
The feeding liquid in the exchange bin 309 is respectively communicated with a plurality of feeding cylinder water inlets 402 through a circulating pump 301 and a pipeline; the control system 1 is electrically connected to the circulation pump 301.
The acid liquid source 9 and the alkaline liquid source 10 can adopt H-rich+Acid solution and HCO-rich3 The alkaline liquid of (2) can be replaced by other required types of liquid.
The control system 1 controls the introduction amount of the clean water source, the gas of each gas source and the acid-base liquid source, and is used for mixing and proportioning the feeding liquid according to the proportion. The control system 1 is powered by a power supply 13. The control system calculates and processes detection signals of each sensor through BreathFish control software, sets output instructions and operation states, monitors feedback information of each sensor in real time, enables the whole system to stably operate in preset states of pressure, flow, gas partial pressure, pH value, temperature, humidity, liquid level height and the like, collects system, environment and biological information, and feeds the information back to the control system, so that precise and automatic regulation and control of the whole circulating device are realized.
Example 4, as shown in fig. 1, 2 and 3, a gas mixing bin 2 is arranged on the connecting pipeline between the multiple gas sources and the exchange membrane gas inlet 303; the various gas sources are O2Gas source 6, CO2Gas source 7, N2A combination of one or more of air source 8, air and other air sources; sensors and control valves are arranged on the various gas sources; a sensor is arranged in the gas mixing bin 2; the control system 1 is respectively and electrically connected with various sensors and control valves on the gas sources and the gas mixing bin 2; the air outlet of the exchange membrane 310 is communicated with the gas mixing bin 2 through a one-way pipeline.
The gas mixing bin 2 comprises an exhaust port 201, a gas mixing bin shell 202, a gas mixing bin sensor 203, O2Inlet 204, CO2Air inlet 205, N2 An air inlet 206 and a mixture air inlet 207.
O2Gas source 6 is through O2The gas inlet 204 enters the gas mixing bin 2; CO 22 Gas source 7 is through CO2The gas inlet 205 enters the gas mixing bin 2; n is a radical of2The gas source 8 passes through N2The gas inlet 206 enters the gas mixing bin 2; air enters the gas mixing bin 2 through a mixture air inlet 207. And a pressure sensor, a flow sensor and a flow control valve which are electrically connected with the control system 1 are respectively arranged on each air source interface channel so as to monitor and control the air input of each air source introduced into the air mixing bin 2. A gas mixing bin sensor 203 electrically connected with the control system 1 is arranged in the gas mixing bin 2, and the gas mixing bin sensor is a gas partial pressure sensor; the gas mixing bin 2 is provided with exhaustPort 201. The control system monitors and regulates the flow of each gas source gas inlet and the partial pressure of the gas entering the gas mixing bin 2.
The exchange membrane gas outlet 308 is communicated with the mixed gas inlet 207 on the gas mixing bin 2 through a one-way pipeline, and redundant mixed gas can enter the gas mixing bin 2 again for recycling.
The specific method for regulating the flow of gas and liquid by the control system is calculated according to the following formula: gas flow V into the gas mixing chamber 2StorehouseShould be equal to the sum of the gas flows of the various gas sources, i.e.
VStorehouse=VO2+VCO2+VN2+VMixing(formula 1)
In order to keep the pressure in the gas mixing bin constant, the gas flow V entering the membrane exchange system 3Film
VFilm=VStorehouse(formula 2)
Therefore, can be derived
VFilm=VStorehouse=VO2+VCO2+VN2+VMixing(formula 3)
Gas pressure P in the gas mixing chamberStorehouseShould be equal to the sum of the partial pressures of the various gas components, i.e.
PStorehouse=PO2+PCO2+PN2+PH2O+POthers(formula 4)
Flow rate F of circulating pump 301Pump and method of operating the sameShould be equal to the sum of the flow rates from the various liquid sources, i.e.
FPump and method of operating the same=FWater purification+FAcid liquor+FAlkali liquor(formula 5)
Meanwhile, the flow F of the feed liquid generated by the exchange chamber 309 in the membrane exchange systemStorehouseEqual to the flow F of the liquid pumped out by the circulation pumpPump and method of operating the sameI.e. by
FStorehouse=FPump and method of operating the same(formula 6)
Flow F of liquid delivered by the circulation pump to the individual tanksCylinderEqual to the total flow F of the liquid at the water inlet of each feeding cylinderCylinderI.e. by
FCylinder=FCylinder 1+FCylinder 2+FCylinder 3+……+FCylinder n(formula 7)
Furthermore, the circulation pump flow FPump and method of operating the sameShould be equal to the sum F of the liquid flow rates at the water inlets of all the feeding cylindersCylinderI.e. by
FPump and method of operating the same=FCylinder(formula 8)
From this it can be derived
FPump and method of operating the same=FStorehouse=FCylinder(formula 9)
According to the formulas 1-9, the gas and liquid flow information collected by the flow sensors at all parts of the device system is fed back to the BreathFish control system, the system accurately calculates the required gas and liquid amount according to the algorithm, and outputs the instruction to the flow control valve, thereby accurately adjusting O2/CO2/N2Gas source quantity H+/CHO3 The flow of the liquid source and the cleaning water maintains the stable operation of the whole system. When the CO is according to the partial pressure of the gas in the gas mixing bin 22The actual demand, BreathFish, determines CO according to the monitored value from the gas partial pressure sensor2If the partial pressure ratio is lower than the expected value, the signal is fed back to CO2Flow control valve on gas source for adding CO2So that CO entering the gas mixing silo2Increasing the partial pressure required; if CO is present2If the partial pressure exceeds the required concentration, a control command is sent to the CO2Flow control valve on gas source for CO reduction2To output of (c).
The smooth operation of the whole membrane exchange system needs to consider the solubility of various air sources dissolved in the mixing bin after passing through the exchange membrane to form premixed water. The solubility of a certain gas in the premixed water is determined by the temperature of the liquid, the partial pressure of the gas, the pressure in the exchange bin and other parameters, and is monitored in real time by sensors at various parts and dynamically adjusted by a control system so as to achieve the dynamic balance required by the experiment.
At different pressure and temperature conditions, O2And CO2And whether other gases are soluble in waterThe same applies. According to Henry's law, the solubility of a certain gas B in solution is proportional to the equilibrium pressure of the gas above the liquid surface at isothermal equal pressures. Which has the formula of
PB=H·XB(formula 10)
In the formula: h is a Henry constant whose value is related to temperature, pressure, and the nature of the solutes and solvents; xBIs the mole fraction solubility of gas B, PBIs the partial pressure of gas B. H can well represent the dissolved amount of gas. Since various concentrations are proportional to each other in a dilute solution, xB in the above formula may be mB (molar mass concentration) or cB (mass concentration of a substance), and the H value in this case changes. And looking up a table to obtain the H value under certain temperature and pressure, and substituting into the calculation to obtain the solubility of the gas. Strictly speaking, the Henry law is an approximate law and is only applicable to systems with low solubility.
When the total pressure is not large, if a plurality of gases are dissolved in the same liquid at the same time, the Henry's law can be respectively applied to any one of the gases; generally, the more dilute the solution, the more accurate the Henry's law, and the more closely the solute can obey the law at X → 0. The temperature is different, the Henry coefficient is different, the temperature is increased, the volatilization capacity of the volatile solute is enhanced, and the Henry coefficient is increased. In other words, the solubility of the gas decreases with increasing temperature at the same partial pressure. If several gases are dissolved in the same solvent to form a dilute solution, the relationship between the equilibrium partial pressure of each gas and its solubility is applied to Henry's law. N in air2、O2And CO2Dissolution in water is an example of this.
The experimental system is a system which can be closed, is not an open system directly communicated with the atmosphere, is provided with a pressure sensor, a gas partial pressure sensor, a temperature sensor and the like at a plurality of parts of the system, can adjust pressurization or depressurization within the allowable pressure range of the system, and operates according to the set pressure state, thereby realizing adjustable and controllable various gas solubilities. Specifically, the standard gas solubility table can be searched according to the solubility under a certain pressure and temperature state. For example, the following table shows the Henry coefficients for several gases dissolved in water at 25 ℃.
Gas (es) H2 N2 O2 CO CO2
Hx 7.2 8.68 4.40 5.79 0.166
In the embodiment 5, the feeding liquid in the exchange bin 309 is respectively communicated with the water inlets of a plurality of feeding cylinders 4 through circulating pumps 301 and pipelines; the plurality of feeding cylinders 4 are arranged in parallel; the control system 1 is electrically connected to the circulation pump 301.
The feeding cylinder 4 comprises a sealing cover 401 and a cylinder body 403; a liquid level sensor and a temperature sensor are arranged in the feeding cylinder 4; the control system 1 is electrically connected with the liquid level sensor and the temperature sensor; the water outlet of the feeding cylinder 4 is communicated with a filtering system through a pipeline; the filtering system comprises a sewage filter 5 and a sewage disposal pool 12 which are communicated in sequence; the clean water outlet of the sewage filter 5 is communicated with the exchange bin 309 through a pipeline; the sewage filter 5 and the sewage disposal pool 12 are respectively provided with a liquid level sensor, a flow sensor and a flow control valve; the control system 1 is electrically connected with the liquid level sensor, the flow sensor and the flow control valve.
The feeding cylinder 4 is provided with an independent sealing cover 401, so that various components in the feeding liquid are prevented from being directly exchanged with the external environment, and the accuracy of experimental data is ensured; the arrangement quantity of the feeding cylinders is not limited, and a plurality of feeding cylinders can be connected in parallel and can be increased or decreased randomly according to specific experimental requirements. Liquid level sensor and temperature sensor monitor the interior liquid level of feeding jar and the temperature condition in 4 feeding jars to with data acquisition feedback to control system, carry out the replenishment of liquid level and the lift of temperature by control system according to the data set requirement, provide suitable environment for the research of zebra fish in the feeding jar.
Example 6, wherein the fish may be selected from zebrafish. The high homology of the genome of the zebra fish and the human genome is utilized as a model organism with outstanding advantages, and a disease model copied by the zebra fish plays an important role in the research of human diseases.
The application of the polypeptide in preparing an animal model simulating the respiratory system of a human.
The application of the compound in preparing an animal model simulating respiratory diseases in human hypoxemia, hyperoxia, hypocapnia and hypercapnia.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (10)

1. An artificial lung system for non-surgically invasive fish, comprising: containing an adjustable culture solution O2Partial pressure, CO2Partial pressure, H+Concentration, HCO3 -Membrane exchange system of any one or several of the parameters of concentration.
2. An artificial lung system for non-surgically invasive fish, comprising: comprises a control system (1), a membrane exchange system (3), a feeding cylinder (4) and a plurality of air sources; the membrane exchange system (3) comprises an exchange bin (309) and an exchange membrane (310); the exchange membrane (310) is arranged in an exchange bin (309) of pre-mixed water; the gas sources are communicated with the gas inlet of the exchange membrane (310); the inside of the membrane (310) is an air cavity, and the outside of the membrane is premixed water; the feeding liquid in the exchange bin (309) is communicated with the water inlets of the plurality of feeding cylinders (4) through pipelines; a plurality of sensors and control valves are arranged on the plurality of gas sources; the control system (1) is electrically connected with various sensors and control valves respectively.
3. The non-surgically invasive fish artificial lung system according to claim 1, wherein: the water inlet of the exchange bin (309) is respectively connected with an acidic liquid source (9), an alkaline liquid source (10) and a cleaning water source (11) through pipelines; the acid liquid source (9), the alkaline liquid source (10) and the clean water source (11) are respectively provided with a plurality of sensors and control valves; the control system (1) is electrically connected with various sensors and control valves on each unit respectively.
4. The non-surgically invasive fish artificial lung system according to claim 1, wherein: a gas mixing bin (2) is arranged on a connecting pipeline between the various gas sources and the gas inlet of the exchange membrane (310); the various gas sources are O2Gas source (6), CO2Gas source (7), N2One or more of a combination of air source (8), air and other air sources; sensors and control valves are arranged on the various gas sources; a sensor is arranged in the gas mixing bin (2); the control system (1) is respectively and electrically connected with various sensors and control valves on the gas sources and the gas mixing bin (2); and the air outlet of the exchange membrane (310) is communicated with the gas mixing bin (2) through a one-way pipeline.
5. The non-surgically invasive fish artificial lung system according to any one of claims 2 to 4, wherein: the sensor comprises one or more of a pressure sensor, a flow sensor, a gas partial pressure sensor, a pH sensor, a temperature sensor, a humidity sensor, a water level sensor and a liquid component sensor.
6. The non-surgically invasive fish artificial lung system according to claim 2 or 3, wherein: the feeding liquid in the exchange bin (309) is respectively communicated with the water inlets of the plurality of feeding cylinders (4) through a circulating pump (301) and a pipeline; the plurality of feeding cylinders (4) are arranged in parallel; the control system (1) is electrically connected with the circulating pump (301).
7. The non-surgically invasive fish artificial lung system according to claim 6, wherein: the feeding cylinder (4) comprises a sealing cover (401) and a cylinder body (403); a liquid level sensor and a temperature sensor are arranged in the feeding cylinder (4); the control system (1) is electrically connected with the liquid level sensor and the temperature sensor; the water outlet of the feeding cylinder (4) is communicated with a filtering system through a pipeline; the filtering system comprises a sewage filter (5) and a sewage disposal pool (12) which are communicated in sequence; the clean water outlet of the sewage filter (5) is communicated with the exchange bin (309) through a pipeline; a liquid level sensor, a flow sensor and a flow control valve are respectively arranged on the sewage filter (5) and the sewage disposal pool (12); the control system (1) is electrically connected with the liquid level sensor, the flow sensor and the flow control valve.
8. The non-surgically invasive fish artificial lung system according to any one of claims 1 or 2, wherein: wherein the fish is selected from zebrafish.
9. The non-surgically invasive fish artificial lung system according to any one of claims 1 or 2, wherein: the application of the polypeptide in preparing an animal model simulating the respiratory system of a human.
10. The non-surgically invasive fish artificial lung system according to claim 9, wherein: the application of the compound in preparing an animal model simulating respiratory diseases in human hypoxemia, hyperoxia, hypocapnia and hypercapnia.
CN201911402410.8A 2019-12-31 2019-12-31 Artificial lung system for non-surgical intervention fish and application thereof Active CN111096255B (en)

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