CN104225698B - A kind of hepatocyte microsphere circulating biological artificial liver support system - Google Patents
A kind of hepatocyte microsphere circulating biological artificial liver support system Download PDFInfo
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- CN104225698B CN104225698B CN201410445472.8A CN201410445472A CN104225698B CN 104225698 B CN104225698 B CN 104225698B CN 201410445472 A CN201410445472 A CN 201410445472A CN 104225698 B CN104225698 B CN 104225698B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
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Abstract
A kind of biological artificial liver support system, comprises blood circulation, blood plasma separating system, hepatocyte microsphere blood circulation three blood circulation.Adopt blood oxygen, PH, blood pressure, temperature integrated sensor, can not only every physiological parameter in real-time monitoring system, and the complexity of whole system is reduced, be convenient to the process of data, simultaneously, adopt hepatocyte microsphere culture fluid storage device and iterative cycles mode, not only increase nutrient substance, the transmittability of oxygen, the longer function of hepatocyte can be maintained with active, be conducive to again fully contacting of hepatocyte and blood plasma, liver failure patient liver function can be substituted in a long time, in addition, hepatocyte microsphere culture fluid storage device arranges culture fluid and extracts mouth and culture fluid interpolation mouth, achieve when influential system does not normally run, extract cell sample, the fresh medium detecting cytoactive and add containing hepatocyte microsphere.
Description
Technical field
The present invention relates to technical field of medical equipment, particularly a kind of hepatocyte microsphere circulating biological artificial liver support system.
Background technology
Biotype artificial liver is product liver cell culture technology combined with blood purification technology, its ultimate principle is the hepatocyte bred by In vitro culture, be placed in special bioreactor, utilize extracorporeal circulation apparatus that hepatic failure patients blood or blood plasma are introduced bioreactor, carry out mass exchange and biological agent by the semipermeable membrane in reactor and hepatocyte.It utilizes hepatocytes secrete endogenous active substance and transforms heterotoxin and play a role, and wherein endogenous active substance comprises various albumen, metabolic enzyme and active factors etc.Bioartificial liver is the artificial liver support system the most close with normal liver, can substitute the functions such as liver detoxification, biosynthesis and secretion metabolism more all sidedly.Biotype artificial liver theoretically, can the repertoire of compensatory liver, and can make up the defect of Non-biotype artificial liver, it relies on the active Hepatocyte be inoculated in bioreactor.Therefore, the new focus that bioartificial liver has become artificial liver research field is built.
Bioreactor is the core apparatus of bioartificial liver, status in bioartificial liver is just equivalent to " heart " of human body, it provides foreign hepatocytes grow and carry out the place of mass exchange with patients blood plasma, and its performance is directly connected to the effect of artificial liver support system.
Now widely used Biotype artificial liver mainly comprises blood circulation and plasma circulation system.Blood circulation is drawn by the blood of human body, through plasma separator, blood separation become blood plasma and hemocyte.Plasma circulation system is that the blood plasma after making separation enters in bioreactor, realizes the objects such as the removing toxic substances of blood plasma.The exocoel of bioreactor places the hepatocyte of In vitro culture propagation, and blood plasma flows through the inner chamber of bioreactor, carries out mass exchange and biological agent by the semipermeable membrane in reactor and hepatocyte.Every physiological parameter in systemic circulation is monitored by a certain class sensor, and the activity of cell detects by extracting cell sample.This technical know-how can realize certain liver function, but come with some shortcomings: 1) can not the running status of Real-Time Monitoring artificial liver support system, also just can not problem in Timeliness coverage and processing system.In addition, adopt a certain class sensor, cause kind of sensor various, not only bad for the process of data, and make the complex structure of system.2) time that the hepatocyte in bioreactor exocoel can only remain shorter owing to lacking support cytoactive, the liver function of hepatic insufficiency patient can only be replaced the short time.
Summary of the invention
In order to overcome the shortcoming of above-mentioned prior art, the object of the invention is to propose a kind of hepatocyte microsphere circulating biological artificial liver support system, replace multiple single-sensor with integrated sensor in biological artificial liver support system, the basis of blood circulation and plasma circulation system adds hepatocyte microsphere blood circulation.It comprises the circulation of hepatocyte microsphere culture fluid and enters bioreactor exocoel and hepatocyte microsphere culture fluid circulation oxygen supply.Adopt sodium alginate as timbering material culture hepatocyte simultaneously, the time that cytoactive keeps longer can be made.It is high that whole system has integration degree, simple to operate, convenient data processing, efficiency high.
In order to achieve the above object, technical scheme of the present invention is achieved in that
A kind of hepatocyte microsphere circulating biological artificial liver support system, comprises blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation.Blood circulation comprises plasma separator 5, the blood entry port of plasma separator 5 is connected with the tremulous pulse of blood oxygen, PH, blood pressure, temperature integrated sensor 4, blood circulation constant-current device 3, vascular clamp 1 and patient successively, heparin pump 2 is connected with the pipeline that bloody path presss from both sides between 1 and blood constant-current device 3 by T-shape tube joint, the hemocyte outlet of plasma separator 5 successively with heater 6, leak blood, Connect of Vein that pressure-detecting device 7, filter, air catcher device 8, bloody path press from both sides 9 and patient, the plasma outlet port of plasma separator 5 is connected with plasma circulation system;
Plasma circulation system comprises hollow-fiber bioreactor 12, the lumen inlet of hollow-fiber bioreactor 12 is connected with the plasma outlet port of plasma separator 5 through oxygenator 11, plasma circulation constant-current device 10 successively, and the chamber exit of hollow-fiber bioreactor 12 exports with the hemocyte of plasma separator 5 and is connected.Hollow-fiber bioreactor 12 is placed on that temperature is 37 DEG C, CO2 concentration is in the calorstat of 5%, and the exocoel outlet of hollow-fiber bioreactor 12, exocoel entrance respectively regulating liver-QI cell microsphere blood circulation connect;
Hepatocyte microsphere blood circulation comprises hepatocyte microsphere culture fluid storage device 13, the hepatocyte microsphere culture fluid entrance a of hepatocyte microsphere culture fluid storage device 13 is connected with the exocoel culture fluid outlet of hollow-fiber bioreactor 12, and the hepatocyte microsphere culture fluid outlet b of hepatocyte microsphere culture fluid storage device 13 is connected with the exocoel culture fluid entrance of hollow-fiber bioreactor 12 by hepatocyte microsphere culture fluid circulation constant-current device 16.Hepatocyte microsphere culture fluid storage device 13 is divided into two A, B two chambers by dividing plate, fresh hepatocyte microsphere culture fluid is stored in A chamber, the hepatocyte microsphere culture fluid through hollow-fiber bioreactor 12 exocoel is stored in B chamber, B chamber outlet f is connected with the entrance g of A chamber for Oxygen cycle constant-current device 15 through oxygenator 14, hepatocyte microsphere culture fluid after being connected with the outlet e of A chamber again, and the A chamber upper surface of hepatocyte microsphere culture fluid storage device 13 has culture fluid and extracts, adds mouth c, sample tap d.
The connecting line that described is inside and outside blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation adopts medical silicone tube or medical poly-third ethylene tube.
Described is blood circulation, plasma circulation system, and hepatocyte microsphere blood circulation is placed in a casing.
The present invention adopts blood oxygen, PH, blood pressure, temperature integrated sensor 4, can not only every physiological parameter in real-time monitoring system, and the complexity of whole system is reduced, and is convenient to the process of data.Simultaneously, adopt the mode of hepatocyte microsphere culture fluid storage device 13 and iterative cycles, not only be conducive to the transmittability improving nutrient substance, oxygen, maintain the activity that hepatocyte is longer, and be conducive to fully contacting of hepatocyte and blood plasma, liver failure patient liver function can be substituted in a long time.In addition, have culture fluid at the A chamber upper surface of hepatocyte microsphere culture fluid storage device 13 to extract, add mouth c, achieve when influential system does not normally run, in hepatocyte microsphere culture fluid storage device 13, add fresh hepatocyte microsphere culture fluid or therefrom extract hepatocyte microsphere culture fluid.Have extraction mouth at the A chamber upper surface of hepatocyte microsphere culture fluid storage device 13, extract cell sample, detect cytoactive.
Accompanying drawing explanation
Accompanying drawing is structural representation of the present invention.
Detailed description of the invention
Below in conjunction with accompanying drawing, structural principle of the present invention and operation principle are described in detail.
With reference to accompanying drawing, a kind of hepatocyte microsphere circulating biological artificial liver support system, comprise blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation, blood circulation comprises plasma separator 5, the blood entry port of plasma separator 5 successively with blood oxygen, PH, blood pressure, temperature integrated sensor 4, blood circulation constant-current device 3, vascular clamp 1 is connected with the tremulous pulse of patient, heparin pump 2 is connected with the pipeline that bloody path presss from both sides between 1 and blood constant-current device 3 by T-shape tube joint, plasma separator 5 hemocyte outlet successively with heater 6, leak blood, pressure-detecting device 7, filter, air catcher device 8, the Connect of Vein of bloody path folder 9 and patient, the plasma outlet port of plasma separator 5 is connected with plasma circulation system,
Plasma circulation system comprises hollow-fiber bioreactor 12, the lumen inlet of hollow-fiber bioreactor 12 is connected with the plasma outlet port of plasma separator 5 through oxygenator 11, plasma circulation constant-current device 10 successively, and the chamber exit of hollow-fiber bioreactor 12 exports with the hemocyte of plasma separator 5 and is connected.Hollow-fiber bioreactor 12 is placed on that temperature is 37 DEG C, CO2 concentration is in the calorstat of 5%, and the exocoel outlet of hollow-fiber bioreactor 12, exocoel entrance respectively regulating liver-QI cell microsphere blood circulation connect;
Hepatocyte microsphere blood circulation comprises hepatocyte microsphere culture fluid storage device 13, the hepatocyte microsphere culture fluid entrance a of hepatocyte microsphere culture fluid storage device 13 is connected with the exocoel culture fluid outlet of hollow-fiber bioreactor 12, and the hepatocyte microsphere culture fluid outlet b of hepatocyte microsphere culture fluid storage device 13 is connected with the exocoel culture fluid entrance of hollow-fiber bioreactor 12 by hepatocyte microsphere culture fluid circulation constant-current device 16.Hepatocyte microsphere culture fluid storage device 13 is divided into two A, B two chambers by dividing plate, fresh hepatocyte microsphere culture fluid is stored in A chamber, the hepatocyte microsphere culture fluid through hollow-fiber bioreactor 12 exocoel is stored in B chamber, B chamber outlet f is connected with the entrance g of A chamber for Oxygen cycle constant-current device 15 through oxygenator 14, hepatocyte microsphere culture fluid after being connected with the outlet e of A chamber again, and the A chamber upper surface of hepatocyte microsphere culture fluid storage device 13 has culture fluid and extracts, adds mouth c, sample tap d.
The connecting line that described is inside and outside blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation adopts medical silicone tube or medical poly-third ethylene tube.
Described is blood circulation, plasma circulation system, and hepatocyte microsphere blood circulation is placed in a casing.
Operation principle of the present invention is: blood circulation medium-sized artery blood through bloody path folder 1, then enters into plasma separator 5 by blood oxygen, blood pressure, PH, temperature integrated sensor 4 under the drive of blood circulation constant-current device 3.Heparin pump 2 adds anticoagulant by T-shape tube joint in blood, prevents blood coagulation.Blood is separated into blood plasma and hemocyte in plasma separator, under the drive of plasma circulation constant-current device 10, blood plasma is first through oxygenator 11, then enter into hollow-fiber bioreactor inner chamber by the lumen inlet of hollow-fiber bioreactor 12, finally flow out from the chamber exit of hollow-fiber bioreactor 12.Meanwhile, the liver cell culture liquid containing the fresh sodium alginate parcel of q.s in the A chamber of hepatocyte microsphere culture fluid storage device 13 enters into the exocoel of bioreactor 12 under the driving of culture fluid constant-current device 16 by the exocoel culture fluid entrance of hollow-fiber bioreactor 12.During the hollow fiber conduit that hepatocyte microsphere in hollow-fiber bioreactor 12 exocoel is made by semipermeable membrane and blood plasma carry out, small-molecule substance exchanges, and completes the liver functions such as synthesis, metabolism, biological conversion.Then in hollow-fiber bioreactor 12 exocoel, hepatocyte microsphere culture fluid is exported by the exocoel culture fluid of this bioreactor, enters into the chamber B of hepatocyte microsphere culture fluid storage device 13.In addition, the hepatocyte microsphere culture fluid through hollow-fiber bioreactor 12 exocoel stored in the fresh hepatocyte microsphere culture fluid stored in chamber A and chamber B flows out from the B chamber outlet f of hepatocyte microsphere culture fluid storage device 13 and A chamber outlet e respectively under the driving of constant-current device 15, through oxygenator 14, then entered into the A chamber of hepatocyte microsphere culture fluid storage device 13 by the entrance g of A chamber, so cyclically give the hepatocyte microsphere oxygen supply with sodium alginate parcel.This not only contributes to making the hepatocyte microsphere entering bioreactor have higher activity, and improves the hepatocellular ratio of high activity in hepatocyte microsphere culture fluid, and the efficiency of system is improved.After mass exchange, the blood plasma of patient is then through the chamber exit of hollow-fiber bioreactor 12, converges with the hemocyte out of the plasma outlet port from plasma separator 5, forms blood and turns back to human vein.The chamber A upper surface of hepatocyte microsphere culture fluid storage device 13 has outlet d for sampling culture fluid, detects wherein each item parameter.The chamber A upper surface of hepatocyte microsphere culture fluid storage device 13 has outlet c then for adding, changing the culture fluid containing hepatocyte microsphere.
Claims (3)
1. a hepatocyte microsphere circulating biological artificial liver support system, comprise blood circulation, plasma circulation system, hepatocyte microsphere blood circulation three blood circulation, it is characterized in that: blood circulation comprises plasma separator (5), the blood entry port of plasma separator (5) successively with blood oxygen, PH, blood pressure, temperature integrated sensor (4), blood circulation constant-current device (3), first bloody path folder (1) is connected with the tremulous pulse of patient, heparin pump (2) by T-shape tube joint with at the first bloody path, the pipeline pressed from both sides between (1) and blood circulation constant-current device (3) is connected, plasma separator (5) hemocyte outlet successively with heater (6), leak blood, pressure-detecting device (7), filter, air catcher device (8), the Connect of Vein of the second bloody path folder (9) and patient, the plasma outlet port of plasma separator (5) is connected with plasma circulation system,
Plasma circulation system comprises hollow-fiber bioreactor (12), the lumen inlet of hollow-fiber bioreactor (12) is successively through the first oxygenator (11), plasma circulation constant-current device (10) is connected with the plasma outlet port of plasma separator (5), the chamber exit of hollow-fiber bioreactor (12) exports with the hemocyte of plasma separator (5) and is connected, it is 37 DEG C that hollow-fiber bioreactor (12) is placed on temperature, CO2 concentration is in the calorstat of 5%, the exocoel outlet of hollow-fiber bioreactor (12), exocoel entrance respectively regulating liver-QI cell microsphere blood circulation connects,
Hepatocyte microsphere blood circulation comprises hepatocyte microsphere culture fluid storage device (13), the hepatocyte microsphere culture fluid entrance a of hepatocyte microsphere culture fluid storage device (13) is connected with the exocoel culture fluid outlet of hollow-fiber bioreactor (12), the hepatocyte microsphere culture fluid outlet b of hepatocyte microsphere culture fluid storage device (13) is connected with the exocoel culture fluid entrance of hollow-fiber bioreactor (12) by hepatocyte microsphere culture fluid circulation constant-current device (16), hepatocyte microsphere culture fluid storage device (13) is divided into two A by dividing plate, B two chambers, fresh hepatocyte microsphere culture fluid is stored in A chamber, the hepatocyte microsphere culture fluid through hollow-fiber bioreactor (12) exocoel is stored in B chamber, B chamber outlet f after being connected with the outlet e of A chamber again through the second oxygenator (14), hepatocyte microsphere culture fluid is connected with the entrance g of chamber A for Oxygen cycle constant-current device (15), the chamber A upper surface of hepatocyte microsphere culture fluid storage device (13) has culture fluid and extracts, add mouth c, sample tap d.
2. a kind of hepatocyte microsphere circulating biological artificial liver support system according to claim 1, is characterized in that: the inside and outside connecting line of blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation adopts medical silicone tube or medical poly-third ethylene tube.
3. a kind of hepatocyte microsphere circulating biological artificial liver support system according to claim 1, is characterized in that: blood circulation, plasma circulation system regulating liver-QI cell microsphere blood circulation are placed in a casing.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106139285B (en) * | 2016-07-29 | 2018-07-06 | 武汉仝干医疗科技股份有限公司 | Four-in-one lint wire type bioartificial liver monitors on-line and heated at constant temperature integrated system |
| CN107012090A (en) * | 2017-03-09 | 2017-08-04 | 刘兴 | A kind of external liver system |
| CN110448749A (en) * | 2019-09-16 | 2019-11-15 | 上海市东方医院（同济大学附属东方医院） | Cell-circulating bioartificial liver device with oxygen supply |
| CN110859635A (en) * | 2019-10-18 | 2020-03-06 | 四川南格尔生物科技有限公司 | Plasma sampling pipeline system and sampling method |
| CN111249552B (en) * | 2020-03-16 | 2020-11-17 | 南京鼓楼医院 | Bioartificial liver based on human iPSCs induced hepatic cell and multilayer porous bioreactor |
| CN116672533A (en) * | 2020-08-19 | 2023-09-01 | 上海心光生物医药有限责任公司 | Medical device |
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