CN201119927Y - Microcapsule suspension type fluidized bed type bioreactor for artificial liver - Google Patents
Microcapsule suspension type fluidized bed type bioreactor for artificial liver Download PDFInfo
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- CN201119927Y CN201119927Y CNU2007201131123U CN200720113112U CN201119927Y CN 201119927 Y CN201119927 Y CN 201119927Y CN U2007201131123 U CNU2007201131123 U CN U2007201131123U CN 200720113112 U CN200720113112 U CN 200720113112U CN 201119927 Y CN201119927 Y CN 201119927Y
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- artificial liver
- fluidized bed
- bioreactor
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Abstract
The utility model belongs to the technical field of medical biology, which relates to a microcapsule suspending-type fluid bed-type bioreactor for artificial liver. The bioreactor takes funnel shaped, whose lower diameter is small and upper diameter is big, the upper neck is provided with a cell screen mesh (8), the lower portion is provided with a cell screen mesh (7), a liquid outlet (2) is provided with a cell filter (11), a small butter cavity (12) is arranged between a liquid inlet (1) and the cell screen mesh (7) and between the cell filter (11) and the cell screen mesh (8), a microencapsulation hepatocyte (9) is arranged between the cell screen mesh (8) and the cell screen mesh (7), a film oxygenator (14) is connected on the outer of the liquid inlet, and an immune adsorber (15) for adsorbing immune macromolecule is connected on the outer of the liquid outlet. Since the bioreactor for artificial liver which is provided by the utility model is designed into a funnel shape, the lower diameter of the container is little, and the upper diameter is big, the path of movement of flow impact is adjustment parabolic curve, which is in accordance with fluid dynamics. The bioreactor for artificial liver effectively avoids perfusion physiological dead space and ineffective perfusion, which can effectively play the treatment function of biological artificial liver.
Description
Technical field
This utility model belongs to field of biomedicine technology, relates to a kind of armarium, a kind of core apparatus---artificial liver microcapsule suspension type fluidized bed type bioreactor for biotype or mixed biology artificial liver treatment.
Background technology
Bioreactor is the core apparatus of biotype and hybrid artificial liver support system, be not only the place that exogenous hepatocyte and patient blood or blood plasma carry out mass exchange, also provide comparatively ideal growing environment for hepatocyte, generally to meet following basic demand as bioreactor for artificial liver: middle micromolecule transmitted in both directions, and the macromolecular substances immunity deadens a guarantee hepatocyte activity and a constant volume.
At present, what wherein application at present was maximum is hollow-fiber bioreactor, but it is inhomogeneous that the shortcoming of hollow-fiber bioreactor is a cell distribution, cell adhesion is poor, hepatocyte can be gathered into bigger agglomerate in actual applications, both influence its growth metabolism function, easily caused the obstruction of semipermeable membrane again, be unfavorable for mass exchange.In order to overcome this shortcoming, hepatocyte is wrapped in the microcapsule of permeability, constituted the hepatocyte of microencapsulation, put in the reaction vessel, also directly carry out perfusion with this with blood plasma/cultivation, made up microcapsule-type suspension type biological reactor artificial liver support system, for the artificial liver treatment provides new trial, the result shows that microcapsule suspension type bioreactor can show its special advantages aspect the raising mass exchange efficient, this efficacy exertion to bioreactor is particularly important, the microencapsulated hepatocyte bioreactor is to take to solidify the design of bed formula bioreactor at first, only be fit to the meiofauna experiment, but after amplifying application limitation is just arranged, be because direct path has caused the hepatocyte low perfusion state of a large amount of microencapsulation, influence the inside and outside mass exchange of microcapsule membrane, and material absorbing, transform function of detoxification, and under the high shear of perfusate, the easier damage of fixed microencapsulated hepatocyte.So adopting the fluidized bed type bioreactor to be more suitable for microencapsulated hepatocyte plays a role in this bioartificial liver system.But traditional bioartificial liver's fluidized bed reactor adopts column type, also has the perfusion dead space under general flow velocity, even the problem of invalid perfusion and border effect, has influenced Supporting Therapy's effect of bioartificial liver.
Summary of the invention
The design's purpose is to provide a kind of microcapsule suspension type fluidized bed type bioreactor that is applicable to biological artificial liver, avoids the perfusion dead space, and easy and simple to handle, cost is low, and effect is stronger.
The design's artificial liver microcapsule suspension type fluidized bed type bioreactor, comprise liquid-inlet, liquid outlet, microcapsule and preflush inlet and sample tap, reactor are the big infundibulate in footpath, little top, footpath, the end, the last cervical region of infundibulate reactor has the cell screen cloth, lower bottom part has the cell screen cloth, and liquid outlet is provided with cellular filter, between liquid-inlet and the cell screen cloth, a little alveolus of buffering is respectively arranged between cellular filter and the cell screen cloth, hold microencapsulated hepatocyte between cell screen cloth and the cell screen cloth; The external membrane oxygenator of liquid-inlet, liquid outlet is external to be used to adsorb immune macromolecular immunoadsorption device.
The diameter of above-mentioned cell screen cloth is 20-40mm, and mesh size 200-300 order, the diameter of cell screen cloth are 60-80mm, mesh size 600-700 order, and the aperture of cellular filter is 1-5um.
Microcapsule and preflush inlet are arranged on 20mm-40mm place, cell screen cloth below, and the preparation valve; Sample tap is arranged on the above 20mm-30mm of cell screen cloth place, the preparation valve.
Present design is further described below:
The design is used for artificial liver with novel microcapsule-type fluidized bed type bioreactor, comprises liquid entrance microcapsule inlet and sample tap, and container appearances is infundibulate, meets the hydrodynamics characteristics.The container bottom footpath is little, the footpath, top is big, filler neck, hopper base have the cell screen cloth in different apertures, microencapsulated hepatocyte for circulating between the last lower screen cloth, upper and lower side connects outlet and inlet respectively, and there is cellular filter in the exit, and there is membrane oxygenator the inlet upstream, there is the immune macromolecular immunoadsorption device of absorption in the outlet downstream, between inlet and outlet and the cell screen cloth a relative relief area is arranged respectively.Chamber housing microencapsulated hepatocyte and reactor activity composition that the infundibulate housing constitutes.The cell screen cloth of filler neck, its diameter 20-40mm, mesh size 200-300 order, the cell screen cloth of hopper base, its cell screen cloth 60-80mm, mesh size 600-700 order, the cellular filter net of hopper outlet, aperture 1-5um.Near the about 20mm-40mm of hopper base cell screen cloth place microcapsule/preflush inlet is arranged, use for inoculation microcapsule and pre-flushing, and inlet has standby valve-off, near filler neck screen cloth 20mm-30mm sample tap is being arranged, sampling usefulness for microcapsule and liquid in the artificial liver therapeutic process has standby valve-off too.Artificial liver of the present invention needs important auxiliary device with the microcapsule suspension type fluidized bed type reactor, one is at the membrane oxygenator near the reactor upstream, one is the immunoadsorption device near reactor downstream, and they and reactor body constitute complete artificial liver microcapsule suspension type fluidized bed type reactor assembly.
The artificial liver that the design provided is designed to infundibulate with novel microcapsule-type fluidized bed type bioreactor, and the container bottom footpath is little, and the footpath, top is big, the impact flow track is demulcent parabola, meet the hydrodynamics characteristics, effectively avoid perfusion dead space and invalid perfusion, effect is stronger.
The cell screen cloth that different apertures are arranged near filler neck, hopper base, microencapsulated hepatocyte for circulating between the last lower screen cloth, upper and lower side connects outlet and inlet respectively, there is membrane oxygenator the inlet upstream, there is an immune macromolecular immunoadsorption device of absorption in the outlet downstream, between inlet and outlet and the cell screen cloth a relative relief area is arranged respectively.
The design's funnel-shaped container can and dwindle according to clinical specific requirement amplification, and the import and export of funnel-shaped container are at the two ends up and down of container, and close container top has the inlet of microcapsule and preflush, near the bottom sample tap is arranged.
Description of drawings
Fig. 1 is the perspective view of the artificial liver of a routine optimal way with the microcapsule suspension type fluidized bed type bioreactor main body.
Fig. 2 is the artificial liver external system supplymentary schematic representation of apparatus of microcapsule suspension type fluidized bed type bioreactor.
The specific embodiment
The present embodiment artificial liver is an infundibulate with microcapsule suspension type fluidized bed type reactor profile, plastics or lucite shell, and size dimension is: long 20cm, funnel top footpath 6cm, footpath, end 3cm, volume is 800ml.Can amplify as required or dwindle during actual fabrication, formulate needed size.
As Fig. 1, shown in Figure 2: 1 is blood/plasma/or culture fluid inlet, enter in the fluidized bed reactor container for blood/plasma/culture fluid, carry out mass exchange with microencapsulated hepatocyte therein, 2 confession blood/plasma/or the culture fluid outlet, 3 for entering the mouth towards liquid/microencapsulated hepatocyte in advance, inject hepatocyte suspension and pour by this inlet in advance towards liquid, 4 is valve, close after the microencapsulated hepatocyte inoculation, 5 is sample tap, for taking a sample in the artificial liver therapeutic process, 6 is the sample tap valve-off, 7 is the cell screen cloth in footpath at the bottom of the hopper reactor, the liquid that flows into through this screen cloth makes the continuous shuttling movement of microencapsulated hepatocyte by fluidization, be convenient to mass exchange, 8 is the big cell screen cloth in microcapsule infundibulate reactor top footpath, from then on liquid after the microencapsulated hepatocyte fluidization flowed out, pass through and stop microencapsulated hepatocyte, 9 is the hepatocyte of microencapsulation, contain hepatocellular microcapsule for external by what generator for microcapsules was made, average diameter 400-500um, under the fluidization of liquid, constantly circulation, carry out mass exchange, 10 is lucite or cabinet, 11 is cellular filter, be for preventing that cell or cell debris from entering the immunoreation that blood flow produces body, 12 is reactor liquid stream relief area, make in order to keep hemodynamic stablizing, 13 is whole infundibulate fluidized bed reactor schematic appearance, and 14 is oxygenator, make that to carry in the oxygen supply fluidized bed reactor microencapsulated hepatocyte behind blood plasma/culture fluid oxygenate required, 15 is the immunoadsorption device, adsorbs the immune macromolecular substances (IgG that a small amount of microcapsule spills, IgM and complement series), prevent to enter body generation immunoreation.
This example is the fluidization that prevents from easily to gather after microcapsule from depositing agglomerating employing liquid, be convenient to the material friendshipization, for solving traditional invalid perfusion of cylindricality development of evil in febrile disease bed bioreactor and low perfusion situation, adopted funnel-shaped design, the microencapsulated hepatocyte that external making is in advance also cultivated becomes the many cells congeries, be seeded in the fluidized bed reactor, part is brought into play hepatocellular alternative functions.
The comparing advantage with fluidized bed reactor in the past and be of this infundibulate fluidized bed reactor:
The design is a kind of hydromechanical microcapsule suspension type fluidized bed type reactor that meets.Because microencapsulated hepatocyte is easy to deposit, and be easy to adhere to each other, be difficult to separately, more outstanding when using the hepatocyte microcapsule especially on a large scale, must take the fluidizing method of liquid stream, the direct perfusion of traditional fixed bed reactors, shearing force is big, has low perfusion state or has relative perfusion dead space, helps the shuttling movement repeatedly of microcapsule with the reactor of fluidized bed type, reduce shearing force, be more conducive to material exchange.Traditional fluidized bed reactor adopts column type, under general flow velocity, also there are perfusion dead space and border effect, adopt the funnel shaped fluidized bed reactor more to meet the hydrodynamics of microcapsule according to hydromechanical characteristics, more favourable microcapsule is cooked the parabola shuttling movement under the fluid effect like this, optimized the fluid effect of microencapsulated hepatocyte, more favourable material exchanges.There is relief area at this funnel type reactor two ends, and liquid stream is relatively steady in the artificial liver process, are keeping hydrodynamics can show special advantages aspect stable.
This bioartificial liver's microcapsule fluidized bed reactor system is that artificial liver has been opened up new way, and function is comparatively comprehensive, and is easy to operate, and it is comparatively reasonable to design, and has good application prospects.
Claims (4)
1, the artificial liver microcapsule suspension type fluidized bed type bioreactor, comprise liquid-inlet (1), liquid outlet (2), microcapsule and preflush inlet (3) and sample tap (5), it is characterized in that: reactor is the big infundibulate (13) in footpath, little top, footpath, the end, the last cervical region of infundibulate reactor has cell screen cloth (8), lower bottom part has cell screen cloth (7), liquid outlet (2) locates to be provided with cellular filter (11), between liquid-inlet (1) and the cell screen cloth (7), a buffering little alveolus (12) is respectively arranged between cellular filter (11) and the cell screen cloth (8), hold microencapsulated hepatocyte (9) between cell screen cloth (8) and the cell screen cloth (7); The external membrane oxygenator of liquid-inlet (1) (14), liquid outlet (2) is external to be used to adsorb immune macromolecular immunoadsorption device (15).
2, artificial liver microcapsule suspension type fluidized bed type bioreactor according to claim 1, it is characterized in that: the diameter of described cell screen cloth (7) is 20-40mm, mesh size 200-300 order, the diameter of described cell screen cloth (8) is 60-80mm, mesh size 600-700 order, the aperture of described cellular filter (11) is 1-5um.
3, artificial liver microcapsule suspension type fluidized bed type bioreactor according to claim 1 is characterized in that: microcapsule and preflush inlet (3) are arranged on 20mm-40mm place, cell screen cloth (8) below, and preparation valve (4); Sample tap (5) is arranged on the above 20mm-30mm of cell screen cloth (7) place, preparation valve (6).
4, artificial liver microcapsule suspension type fluidized bed type bioreactor according to claim 1 is characterized in that: the spatial altitude that cushions little alveolus (12) is 15mm-20mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2007201131123U CN201119927Y (en) | 2007-08-13 | 2007-08-13 | Microcapsule suspension type fluidized bed type bioreactor for artificial liver |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNU2007201131123U CN201119927Y (en) | 2007-08-13 | 2007-08-13 | Microcapsule suspension type fluidized bed type bioreactor for artificial liver |
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| CN201119927Y true CN201119927Y (en) | 2008-09-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNU2007201131123U Expired - Lifetime CN201119927Y (en) | 2007-08-13 | 2007-08-13 | Microcapsule suspension type fluidized bed type bioreactor for artificial liver |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101549179B (en) * | 2009-04-30 | 2011-09-14 | 浙江大学 | Perforated brick type filling support type reactor used in artificial liver |
| CN101711898B (en) * | 2009-12-14 | 2012-05-23 | 浙江大学 | Microcapsule suspension stirring pool type bioreactor for artificial liver |
| CN104958795A (en) * | 2015-06-23 | 2015-10-07 | 四川大学华西医院 | Whole blood perfusion bioartificial liver system |
-
2007
- 2007-08-13 CN CNU2007201131123U patent/CN201119927Y/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101549179B (en) * | 2009-04-30 | 2011-09-14 | 浙江大学 | Perforated brick type filling support type reactor used in artificial liver |
| CN101711898B (en) * | 2009-12-14 | 2012-05-23 | 浙江大学 | Microcapsule suspension stirring pool type bioreactor for artificial liver |
| CN104958795A (en) * | 2015-06-23 | 2015-10-07 | 四川大学华西医院 | Whole blood perfusion bioartificial liver system |
| CN104958795B (en) * | 2015-06-23 | 2017-03-29 | 四川大学华西医院 | Whole blood perfusion bioartificial liver system |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| AV01 | Patent right actively abandoned |
Effective date of abandoning: 20070813 |
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| C25 | Abandonment of patent right or utility model to avoid double patenting |