CN103170021A - Deflector-type micro-capsule suspension type fluidized bed bioreactor for artificial liver - Google Patents
Deflector-type micro-capsule suspension type fluidized bed bioreactor for artificial liver Download PDFInfo
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- CN103170021A CN103170021A CN2013101245694A CN201310124569A CN103170021A CN 103170021 A CN103170021 A CN 103170021A CN 2013101245694 A CN2013101245694 A CN 2013101245694A CN 201310124569 A CN201310124569 A CN 201310124569A CN 103170021 A CN103170021 A CN 103170021A
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Abstract
The invention discloses a deflector-type micro-capsule suspension type fluidized bed bioreactor for an artificial liver. The deflector-type micro-capsule suspension type fluidized bed bioreactor for the artificial liver comprises an end cover part, a main body part and a base part, wherein the base part comprises an inlet buffer tank, a fixed turbine guide vane, and an inlet filter net arranged at the joint surface of the base part and a subject part; the main body part comprises a cylindrical containing cavity, a sampling and micro-capsule pouring lip and a valve; the sampling and micro-capsule pouring lip and the valve are arranged in a housing of the main body part; and the top cover part comprises an outlet buffer tank, and an outlet filter net arranged at the joint surface of the subject part and the top cover part. By adopting the sealed structure and a multi-opening design, the microencapsulated hepatocyte can be conveniently sampled and added; and meanwhile, the possibility of pollution in an operation process is reduced. The turbine guide vane of the base part can disperse large local flow speed at the inlet; micro-capsule damage is reduced; and the blood purification efficiency is improved. By adopting the deflector-type micro-capsule suspension type fluidized bed bioreactor for the artificial liver, the contact efficiency of the cultivated cell in the bioreactor and perfusate can be improved; meanwhile, the cyclic purification efficiency of the biological part in an artificial liver system is improved; and clinic application is facilitated.
Description
Technical field
The invention belongs to field of biomedicine technology, relate to a kind of armarium, is the core apparatus of specific Biotype artificial liver or hybrid artificial liver.
Background technology
Bioreactor is the core apparatus of Biotype artificial liver system or hybrid artificial liver system, and its function is mainly to possess sufficient capacity and usefulness to provide patient's blood plasma and exogenous hepatocyte to carry out mass exchange, need possess simultaneously the ability of immunity isolation.Previously study hotspot and the present types of bioreactors that has entered clinical trial are mainly hollow fiber reactors, but it exists cell distribution inhomogeneous, low poor activity, the shortcomings such as semipermeable membrane obstruction of reaching of cell adhesion rate.It is found that simultaneously the microcapsule shell that microencapsulated hepatocyte is useful on bioartificial liver's potential value-parcel cell is similar to semipermeable membrane, can carry out mass exchange and immunity isolation, the cell in microcapsule can three dimensional growth, thereby with better function.Its subsequent experimental has also proved the advantage of its uniqueness aspect the material permeability.But the larger defective of the same existence of the fixed bedreactor that is complementary with it--in operation process, many microencapsulated hepatocytes are in low perfusion state, and the suffered shearing force of microencapsulated hepatocyte is larger.for these shortcomings, this laboratory has been researched and developed artificial liver microcapsule suspension type fluidized bed type bioreactor (patent No.: ZL 200820167026.5) and matching used dual-cavity liquid storage tank for biological artificial liver support system (patent No.: ZL 200710070279.0), and built a novel bioartificial liver system of cover take it as core, animal experiment shows that this system has good curative effect, simultaneously also find the place that it still has some to improve: 1. need higher flow rate of liquid just can make microencapsulated hepatocyte suspend fully and fluidisation in reactor, but the hydrodynamic shear that the microcapsule of parcel cell can bear is limited, 2. the hydrodynamics test confirms that there is the dead space that flows in infundibulate fluidized bed type bioreactor, and the part microencapsulated hepatocyte can not fully contact fluidisation liquid, 3. artificial liver is less with microcapsule suspension type fluidized bed type bioreactor (patent No.: ZL 200820167026.5) liquid-inlet, improving flow velocity can cause import localized liquid flow velocity too fast, the suffered hydrodynamic shear of local microcapsule is excessive, and then causes the microcapsule percentage of damage to increase.4. reactor is imported and exported and must be detected dissolved oxygen content, and previously the contact measurement method can't guarantee the biological safety in therapeutic process.
Summary of the invention
The present invention is directed to the deficiency of existing apparatus and system, a kind of artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor is provided.This bioreactor utilizes the high-velocity fluid of turbine flow-guiding type import shunting import part, under the prerequisite that guarantees the microcapsule integrity, improves biological cycle usefulness, in import and export, the unidirectional drainage valve is set simultaneously, facilitates the monitoring of PH and dissolved oxygen.
A kind of artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor, integral body is cylindrical, comprises end cap portions, main part and base portion; Top cover portion comprises the outlet Buffer Pool, is positioned at the outlet screen cloth of main part and top cover portion (15) interface, and the end cap portions top is provided with liquid outlet, and the bottom of liquid outlet is provided with out the mouth cells filter screen; Main part comprises cylindrical content cavity, and the main part shell is provided with sampling and microcapsule perfusing hole, and sampling and microcapsule perfusing hole are provided with valve; Base portion comprises entrance Buffer Pool, turbine type guide vane, be positioned at the inlet screen of base portion and main part interface, be positioned at liquid-inlet and entrance Buffer Pool interface enter the mouth cells filter screen, the base portion bottom is provided with liquid-inlet.
Described liquid-inlet and liquid outlet diameter are 4-8mm, and liquid-inlet is provided with the first unidirectional drainage formula valve, and liquid outlet is provided with the second unidirectional drainage formula valve can unidirectionally draw perfusion liquid for sampling.
The aperture that describedly enter the mouth cells filter screen, goes out the mouth cells filter screen is 1-5 μ m, and described inlet screen diameter is 10-30cm, and aperture of filter screen is 100-500 μ m, and described outlet screen cloth diameter is 10-30cm, and mesh size is the 500-800 order.
Described turbine type guide vane is fixed in base portion, and guide vane is the 8-32 sheet, and the fan-shaped import of each flow-guiding channel and fan-shaped outlet are at the projection zero lap area of transverse section.
Described cylindrical content cavity volume is 500-1500mL.
Described outlet Buffer Pool spatial altitude is 10-30mm, and described entrance Buffer Pool spatial altitude is 10-20mm.
The invention has the beneficial effects as follows: the present invention and dual-cavity liquid storage tank for biological artificial liver support system (patent No.: ZL 200710070279.0) form the high-performance bio peripheral passage, make biological cycle path flow velocity be increased to 300-500ml/min by the turbine type guide vane, and microcapsule lateral shear power is all less than broken marginal value.Brand-new the fluidisation pattern---outer buttons turns to, and the middle part is downward, can avoid occurring the circulation dead space, guarantees fully contacting of microcapsule and fluidisation liquid, the raising purification efficiency.Import and export the one-way guide flow valve and guaranteeing to detect for PH monitoring, dissolved oxygen the sampling approach that provides under the biological safety prerequisite.
Volume of the present invention can amplify according to actual clinical and Research Requirements and dwindle, and for new approach has been opened up in the clinical practice of biotype artificial liver system, its purification efficiency bioreactor is more in the past compared and is significantly improved, and has good application prospect.
Description of drawings
Fig. 1 artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor structural representation.
Fig. 2 artificial liver external artificial liver systematic treating of flow-guiding type microcapsule suspension type fluidized bed type bioreactor schematic diagram.
In figure: 1. liquid outlet, 2. the second unidirectional drainage formula valve, 3. import cell filter screen, 4. the outlet screen cloth, 5. valve, 6. sampling and microcapsule perfusing hole, 7. inlet screen, 8. the turbine type guide vane, 9. enter mouth cells filter screen, 10. the first unidirectional drainage formula valve; 11. liquid-inlet; 12. outlet Buffer Pool; 13. cylindrical content cavity; 14. entrance Buffer Pool; 15. end cap portions; 16. main part; 17. base portion; 18. treatment patient; 19. arterial end; 20. main blood pump; 21. plasma separator; 22. liquid storage tank outer circulation entrance; 23. liquid storage tank internal recycle outlet; 24. oxygenating column; 25. the special-purpose high speed pump of biological cycle; 26. flow-guiding type microcapsule suspension type fluidized bed type bioreactor; 27. liquid storage tank internal recycle import; 28. liquid storage tank outer circulation outlet; 29. bilirubin adsorption device; 30. hemocyte; 31. reflux pump; 32. vein end; 33. biological cycle.
Specific embodiments
The present invention is further described below in conjunction with drawings and Examples.
As shown in Figure 1, flow-guiding type microcapsule suspension type fluidized bed type bioreactor outward appearance of the present invention is cylindrical, comprises end cap portions 15, main part 16 and base portion 17; Top cover portion 15 comprises outlet Buffer Pool 12, be positioned at the outlet screen cloth 4 of main part 16 and top cover portion 15 interfaces, and end cap portions 15 tops are provided with liquid outlet 1, and the bottom of liquid outlet 1 is provided with out mouth cells filter screen 3; Main part 16 comprises cylindrical content cavity 13, and main part 16 sidewalls are provided with sampling and microcapsule perfusing hole 6, and sampling and microcapsule perfusing hole 6 are provided with valve 5; Base portion 17 comprises entrance Buffer Pool 14, turbine type guide vane 8, be positioned at base portion 17 and main part 16 interfaces inlet screen 7, be positioned at liquid-inlet 11 and entrance Buffer Pool interface enter mouth cells filter screen 9, base portion 17 bottoms are provided with liquid-inlet 11.Enclosed construction, microencapsulated hepatocyte conveniently be sampled and be added to many open design can, and the pollution that reduces simultaneously in operating process may.
Wherein: liquid-inlet 11 and liquid outlet 1 diameter are 4-8mm; Import cell filter screen 3, the aperture that enters mouth cells filter screen 9 are 1-5 μ m; Inlet screen 7 diameters are 10-30cm, and aperture of filter screen is 100-500 μ m; Outlet screen cloth 4 diameters are 10-30cm, and mesh size is the 500-800 order; Turbine type guide vane 8 guide vanes are the 8-32 sheet, and the fan-shaped import of each flow-guiding channel and fan-shaped outlet are at the projection zero lap area of transverse section; Cylindrical content cavity 13 volumes are 500-1500mL; Outlet Buffer Pool 12 spatial altitudes are 10-30mm; Entrance Buffer Pool 14 spatial altitudes are 10-20mm.
The test of three dimensional fluid mechanical model and entity all confirms, the present invention forms on stable surrounding screw than interior at specific flow velocity/strong body diameter, middle downward fluid effect, and without the fluidisation dead space of sustainable existence.8 shuntings can make local velocity significantly reduce through the turbine type guide vane, effectively reduce the suffered lateral shear power of microcapsule in the fluid field of force, reduce microcapsule and destroy.
Further, this liquid reactor import 11 and liquid outlet 1 all are equipped with unidirectional drainage formula valve 10,2, can unidirectional liquid of drawing on a small quantity in circulation, and so that being provided, PH and dissolved oxygen detect.
Further, the material of each sidewall of main part of this reactor is medical plastic or lucite, can observe easily the height of liquid storage tank and inner chamber liquid level.
Embodiment
As shown in Figure 2, the artificial liver of the present invention is the core component of biological cycle 33 in biotype artificial liver system with the flow-guiding type microcapsule suspension type fluidized bed type bioreactor.Now simple Biotype artificial liver treatment pattern as example, is introduced specific embodiments of the present invention in Fig. 2.
Treatment is prepared, and opens valve 5, and the hepatocyte that microcapsule is coated is closed the perfusing hole valve after the microcapsule perfusion is complete in sampling and microcapsule perfusing hole 6 pour into reactor body section 16 cylindrical content cavity, from the slow circular buffering liquid for preparing of pre-punching of liquid-inlet 11.Discharge all bubbles and check system seal in circulation line.This moment, less than the microcapsule diameter, microcapsule lodged in reactor body section bottom due to the aperture of inlet screen.
The treatment beginning, treatment patient 18 whole bloods are drawn from arterial end 19, be blood plasma and hemocyte through main blood pump 20 to plasma separator 21 with separation of whole blood, wherein blood plasma enters biological cycle 33, the hemocyte of separation 30 and the blood plasma of completing biological cycle again can with through reflux pump 31 from vein end 32 adoptive therapy patients 18.
The plasma fraction that separates through blood plasma separator 21 enters the circulation liquid storage tank by liquid storage tank outer circulation entrance 22, and all via liquid storage tank internal recycle outlet 23 beginning biological cycle.at first the blood plasma that enters biological cycle pass through oxygenating column 24, make the circulating plasma dissolved oxygen concentration raise to supply the needs of the hepatocyte physiological activity in reactor, with entering flow-guiding type microcapsule suspension type fluidized bed type bioreactor 26 by the special-purpose high speed pump 25 of biological cycle, enter the high flow rate blood plasma of reactor through entrance Buffer Pool 14 bufferings, and via turbine type guide vane 8 water conservancy diversion that are fixed in base portion 17, shunting forms flow velocity and delays and spiralling plasma flow, the microcapsule formation outer buttons that drives simultaneously in reactor turns to, the stabilization fluid state that the middle part is downward, exit blood plasma is via slurry outlet screen cloth 4, outlet Buffer Pool 12 autoreactor liquid outlets 1 evenly flow out.Reactor backflow blood plasma is got back in the circulation liquid storage tank through liquid storage tank internal recycle import 27, wherein the overwhelming majority enters biological cycle through liquid storage tank internal recycle outlet 23 again, with the sufficient detoxifcation of blood plasma experience biological cycle as much as possible, acquisition and the metabolism that guarantees to feed back the body circulation, the blood cell composition feedback human body that the blood plasma after small part repeatedly circulates can separate with plasma separator 21 via liquid storage tank outer circulation outlet 28.
The present invention has significantly improved the flow velocity of biological cycle under the prerequisite that guarantees the microcapsule integrity, make the efficient of biological cycle be demonstrated fully; The discrepancy in elevation speed ratio of simultaneously inside and outside circulation makes the patient to draw flow velocity with less whole blood to reach identical blood purification effect, avoid central vein catheter, arteriovenous to make the complex operations such as basket, provide better therapeutic scheme aspect minimizing patient suffering and easy clinical manipulation.
The above is only a specific embodiment of the present invention, does not consist of any limitation of the invention.All any modifications of doing within the spirit and principles in the present invention, be equal to and replace and improvement etc., within all should being included in protection scope of the present invention.
Claims (6)
1. an artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor, is characterized in that, its integral body is cylindrical, comprises end cap portions (15), main part (16) and base portion (17); Top cover portion (15) comprises outlet Buffer Pool (12), is positioned at the outlet screen cloth (4) of main part (16) and top cover portion (15) interface, end cap portions (15) top is provided with liquid outlet (1), and the bottom of liquid outlet (1) is provided with out mouth cells filter screen (3); Main part (16) comprises cylindrical content cavity (13), and main part (16) shell is provided with sampling and microcapsule perfusing hole (6), and sampling and microcapsule perfusing hole (6) are provided with valve (5); Base portion (17) comprises entrance Buffer Pool (14), turbine type guide vane (8), be positioned at base portion (17) and main part (16) interface inlet screen (7), be positioned at liquid-inlet (11) and entrance Buffer Pool interface enter mouth cells filter screen (9), base portion (17) bottom is provided with liquid-inlet (11).
2. artificial liver according to claim 1 flow-guiding type microcapsule suspension type fluidized bed type bioreactor, it is characterized in that, described liquid-inlet (11) and liquid outlet (1) diameter are 4-8mm, liquid-inlet (11) is provided with the first unidirectional drainage formula valve (10), and liquid outlet (1) is provided with the second unidirectional drainage formula valve (2) can unidirectionally draw perfusion liquid for sampling.
3. artificial liver according to claim 1 flow-guiding type microcapsule suspension type fluidized bed type bioreactor, it is characterized in that, the aperture that describedly enter mouth cells filter screen (9), goes out mouth cells filter screen (3) is 1-5 μ m, described inlet screen (7) diameter is 10-30cm, aperture of filter screen is 100-500 μ m, described outlet screen cloth (4) diameter is 10-30cm, and mesh size is the 500-800 order.
4. artificial liver according to claim 1 flow-guiding type microcapsule suspension type fluidized bed type bioreactor, it is characterized in that, described turbine type guide vane (8) is fixed in base portion (17), guide vane is the 8-32 sheet, and the fan-shaped import of each flow-guiding channel and fan-shaped outlet are at the projection zero lap area of transverse section.
5. artificial liver according to claim 1 flow-guiding type microcapsule suspension type fluidized bed type bioreactor, is characterized in that, described cylindrical content cavity (13) volume is 500-1500mL.
6. artificial liver according to claim 1 flow-guiding type microcapsule suspension type fluidized bed type bioreactor, it is characterized in that: described outlet Buffer Pool (12) spatial altitude is 10-30mm, described entrance Buffer Pool (14) spatial altitude is 10-20mm.
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Cited By (7)
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|---|---|---|---|---|
| CN103877631A (en) * | 2014-03-06 | 2014-06-25 | 浙江大学 | Bioartificial liver system |
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
| CN105176818A (en) * | 2015-09-14 | 2015-12-23 | 南方医科大学珠江医院 | Animal cell microgravity suspension culture system |
| CN105498005A (en) * | 2016-01-22 | 2016-04-20 | 浙江省人民医院 | Acellularized scaffold type bioreactor for artificial liver and utilization method of acellularized scaffold type bioreactor for artificial liver |
| CN106075625A (en) * | 2016-08-26 | 2016-11-09 | 合肥市力维生物科技有限公司 | A kind of Biotype artificial liver |
| CN110205245A (en) * | 2019-06-14 | 2019-09-06 | 科先医疗科技(苏州)有限公司 | A kind of cell reactor for Biotype artificial liver |
| CN112391286A (en) * | 2019-08-14 | 2021-02-23 | 天津理工大学 | A porous support perfusion device for inoculating cell |
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| CN101711898A (en) * | 2009-12-14 | 2010-05-26 | 浙江大学 | Microcapsule suspension stirring pool type bioreactor for artificial liver |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877631A (en) * | 2014-03-06 | 2014-06-25 | 浙江大学 | Bioartificial liver system |
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
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| CN110205245B (en) * | 2019-06-14 | 2022-07-08 | 科先医疗科技(苏州)有限公司 | Cell reactor for biological artificial liver support system |
| CN112391286A (en) * | 2019-08-14 | 2021-02-23 | 天津理工大学 | A porous support perfusion device for inoculating cell |
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Application publication date: 20130626 |