CN203244625U - Flow guiding type minitype capsule suspension fluidized bed bioreactor for artificial liver - Google Patents

Flow guiding type minitype capsule suspension fluidized bed bioreactor for artificial liver Download PDF

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Publication number
CN203244625U
CN203244625U CN 201320179796 CN201320179796U CN203244625U CN 203244625 U CN203244625 U CN 203244625U CN 201320179796 CN201320179796 CN 201320179796 CN 201320179796 U CN201320179796 U CN 201320179796U CN 203244625 U CN203244625 U CN 203244625U
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fluidized bed
outlet
type
inlet
artificial liver
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CN 201320179796
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李兰娟
俞亮
喻成波
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Zhejiang University ZJU
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Zhejiang University ZJU
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Abstract

The utility model discloses a flow guiding type minitype capsule suspension fluidized bed bioreactor for an artificial liver. The flow guiding type minitype capsule suspension fluidized bed bioreactor comprises an end cover part, a body part and a base part which comprises an inlet buffering pool, a fixed turbo type flow guiding vane and an inlet filter screen assembled on the joint face of the base part and the body part. The body part comprises a cylindrical inner containing cavity, a sampling and minitype capsule injection opening formed in an outer shell of the body part, and a valve. The end cover part comprises an outlet buffering pool and an outlet screen assembled on the joint face of the body part and the end cover part. The flow guiding type minitype capsule suspension fluidized bed bioreactor is of a sealed structure and in multi-opening design, sampling is convenient, minitype capsule liver cells can be added conveniently, and meanwhile pollution probability in an operation process can be reduced. The turbo type flow guiding vane on the base part can disperse large flow speed at part of an inlet, minitype capsule damage is lowered, and blood purifying efficiency is improved. The flow guiding type minitype capsule suspension fluidized bed bioreactor can improve contacting efficiency of cells cultured in the bioreactor and injection liquid, and meanwhile circulation purifying efficiency of a biology part of an artificial liver system is improved, and clinical application is convenient.

Description

A kind of artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor
Technical field
This utility model belongs to field of biomedicine technology, relates 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 mainly is 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 mainly are hollow fiber reactors, but it exists cell distribution inhomogeneous, the low and poor activity of cell adhesion rate, the shortcomings such as semipermeable membrane obstruction.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 the 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--many microencapsulated hepatocytes are in low perfusion state in the operation process, 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 made up the novel bioartificial liver system of a 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 ability in the reactor so that microencapsulated hepatocyte suspends and fluidisation fully, 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 the therapeutic process.
Summary of the invention
This utility model provides a kind of artificial liver flow-guiding type microcapsule suspension type fluidized bed type bioreactor for the deficiency of existing apparatus and system.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, makes things convenient for 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 pedestal part; 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; Pedestal part comprises entrance Buffer Pool, turbine type guide vane, be positioned at the inlet screen of pedestal part and main part interface, be positioned at liquid-inlet and entrance Buffer Pool interface enter the mouth cells filter screen, the pedestal part 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 the perfusate body 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 pedestal part, 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 beneficial effects of the utility model are: this utility model and dual-cavity liquid storage tank for biological artificial liver support system (patent No.: ZL 200710070279.0) form the high-performance bio peripheral passage, so that biological cycle path flow velocity is increased to 300-500ml/min, and microcapsule lateral shear power is all less than broken marginal value by the turbine type guide vane.Brand-new the fluidisation pattern---outer buttons turns to, and the middle part is downward, can avoid occurring the circulation dead space, and what guarantee microcapsule and fluidisation liquid fully contacts the raising purification efficiency.Import and export the one-way guide flow valve and guaranteeing to detect the sampling approach that provides for PH monitoring, dissolved oxygen under the biological safety prerequisite.
Volume of the present utility model 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 more in the past bioreactor is 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 sketch map.
Among the 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. pedestal part; 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
Below in conjunction with drawings and Examples this utility model is further specified.
As shown in Figure 1, this utility model flow-guiding type microcapsule suspension type fluidized bed type bioreactor outward appearance is cylindrical, comprises end cap portions 15, main part 16 and pedestal part 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 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; Pedestal part 17 comprises entrance Buffer Pool 14, turbine type guide vane 8, be positioned at pedestal part 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, pedestal part 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 the 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, this utility model specific flow velocity/strong body diameter than interior form stable around on the screw, 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 the 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, this utility model artificial liver is the core component of biological cycle 33 in the biotype artificial liver system with the flow-guiding type microcapsule suspension type fluidized bed type bioreactor.Now simple Biotype artificial liver treatment pattern is introduced this utility model specific embodiments as example in Fig. 2.
Valve 5 is opened in the treatment preparation, and the hepatocyte that microcapsule is coated with pours in the reactor body section 16 cylindrical content cavity through sampling and microcapsule perfusing hole 6, closes the perfusing hole valve after the microcapsule perfusion is complete, slowly rushes in advance the circular buffering liquid for preparing from liquid-inlet 11.Discharge all bubbles and check system seal in the circulation line.This moment since the aperture of inlet screen less than the microcapsule diameter, microcapsule lodges in reactor body section bottom.
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 finishing 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.The blood plasma that enters biological cycle at first passes through oxygenating column 24, so that the circulating plasma dissolved oxygen concentration raises to supply the needs of the hepatocyte physiological activity in the 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 pedestal part 17, shunting forms the slow and spiralling plasma flow of flow velocity, the microcapsule formation outer buttons that drives simultaneously in the 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.
This utility model has significantly improved the flow velocity of biological cycle under the prerequisite that guarantees the microcapsule integrity, so that the efficient of biological cycle is demonstrated fully; The discrepancy in elevation speed ratio of simultaneously inside and outside circulation reaches identical blood purification effect so that the patient can draw flow velocity with less whole blood, avoid central vein catheter, arteriovenous to make the complex operations such as basket, provide better therapeutic scheme aspect minimizing patient suffering and the easy clinical manipulation.
The above only is a specific embodiment of the present utility model, does not consist of any restriction of the present utility model.All any modifications of within spirit of the present utility model and principle, doing, be equal to and replace and improvement etc., all should be included within the protection domain of the present utility model.

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 pedestal part (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); Pedestal part (17) comprises entrance Buffer Pool (14), turbine type guide vane (8), be positioned at pedestal part (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), pedestal part (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 the perfusate body 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 pedestal part (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.
CN 201320179796 2013-04-11 2013-04-11 Flow guiding type minitype capsule suspension fluidized bed bioreactor for artificial liver Expired - Fee Related CN203244625U (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103170021A (en) * 2013-04-11 2013-06-26 浙江大学 Deflector-type micro-capsule suspension type fluidized bed bioreactor for artificial liver

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103170021A (en) * 2013-04-11 2013-06-26 浙江大学 Deflector-type micro-capsule suspension type fluidized bed bioreactor for artificial liver

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Granted publication date: 20131023

Termination date: 20190411