CN102210892A - Integrated microcapsule suspension fluidized bed bioreactor - Google Patents
Integrated microcapsule suspension fluidized bed bioreactor Download PDFInfo
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Abstract
The invention discloses an integrated microcapsule suspension fluidized bed bioreactor, which is formed by the threaded connection of an end cover part and a main body part, wherein a first cavity in the end cover part is in threaded connection with a second cavity in the main body part to form a funnel-shaped inner cavity commonly; an outer cavity is formed between the side wall of the inner cavity and a shell of the bioreactor; the inner cavity is communicated with the outer cavity by a liquid channel formed inside a shell of the end cover part; the outer cavity is partitioned into an upper liquid storage tank, an oxygenation area and a lower liquid storage tank sequentially from top to bottom by a first partition plate and a second partition plate; liquid in the upper liquid storage tank flows into the lower liquid storage tank by a hollow fiber inner cavity of an oxygenator, and returns to the inner cavity of the bioreactor by a liquid inlet pump of the inner cavity from a liquid outlet of the lower liquid storage tank so as to realize the circulating perfusion of blood plasma of treatment objects.
Description
Technical field
The invention belongs to field of biomedicine technology, relate to a kind of armarium, is the specific bioartificial liver or the core apparatus of hybrid artificial liver.
Background technology
Liver failure mortality rate height is high, the internal medicine conservative treatment poor effect, old friends just are being devoted to the especially R﹠D work of biotype and hybrid artificial liver of all kinds artificial liver, expect that they can substitute the liver that disease decreases and carry out correlation function, help patient's self-rehabilitation or wait for liver transplantation.Bioreactor is the core apparatus of bioartificial liver and hybrid artificial liver, and it not only will provide patient's blood plasma and exogenous hepatocyte to carry out the place of mass exchange, also need possess immune isolating power and certain capacity.Hollow-fiber bioreactor is present most popular bioreactor, but it exists cell distribution inhomogeneous, the low and poor activity of cell adhesion rate, and shortcomings such as semipermeable membrane obstruction are so people are are constantly researching and developing various new-type bioreactors.It is found that in recent years microencapsulated hepatocyte is useful on bioartificial liver's potential value--the microcapsule shell of parcel cell is similar to semipermeable membrane, can carry out mass exchange and immunity is isolated, and the cell in the microcapsule can three dimensional growth, thereby with better function.After this people have invented the fixed bedreactor that is applicable to microencapsulated hepatocyte, experimental results show that its special advantages aspect the material permeability.Yet there is bigger defective in the follow-up fixed bedreactor of discovering--many microencapsulated hepatocytes are in low perfusion state in the operation process, and the suffered shearing force of microencapsulated hepatocyte is bigger.At these shortcomings, (China Patent No.: be that core has made up the novel bioartificial liver system of a cover ZL200710070279.0), animal experiment shows that this system has good curative effect to prior art with microcapsule suspension type fluidized bed type bioreactor with artificial liver.But find that also (China Patent No.: the neoplasm artificial liver system that ZL200710070279.0) forms has some need improve and improve local: the only disposable reactor that passes through of (1) patient's blood plasma with microcapsule suspension type fluidized bed type bioreactor by this artificial liver, mass exchange is not enough, needs device and makes the plasma circulation perfusion of drawing in the subject from treatment in reactor.(2) limited from the flow velocity for the treatment of the blood plasma of drawing in the subject, and reactor needs higher flow rate of liquid could make microencapsulated hepatocyte suspend fully and fluidisation.(3) hepatocyte in the bioreactor needs suitable oxygen supply, with persistent maintenance function and vigor, and is far from being enough with the entrained oxygen of treatment target blood plasma without oxygenator supply oxygen only.(4) (China Patent No.: the inlet of microencapsulated hepatocyte is less ZL200710070279.0), and is not too convenient to reactor inner chamber adding microencapsulated hepatocyte with microcapsule suspension type fluidized bed type bioreactor for artificial liver.The liquid storage tank of peripheral hardware and oxygenator can solve above-mentioned (1) to (a 3) problem, but this will make device increase, and also need relative bigger calorstat to place said apparatus, and it is more loaded down with trivial details to operate, and system takes up room big too, is unfavorable for clinical practice.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, a kind of integrated form microcapsule suspension type fluidized bed type bioreactor of the perfusion of self can realizing circulating is provided.
For achieving the above object, the technical solution used in the present invention is: this integrated form microcapsule suspension type fluidized bed type bioreactor is made up of end cap portions and main part, be provided with first cavity in the described end cap portions, be provided with second cavity in the described main part, the upper end of described second cavity is threaded with the lower end of first cavity and forms the funnel type content cavity jointly; Be provided with content cavity first liquid outlet in the crown center zone of end cap portions, the inboard of content cavity first liquid outlet is fixed with first cellular filter; Zone line is provided with the content cavity liquid inlet in the bottom of main part, and the inboard of described content cavity liquid inlet is fixed with second cellular filter; The lower end of the shell of described end cap portions is threaded with the upper end of the shell of described main part and forms the shell of described bioreactor jointly, and cavity volume outside forming between the inboard of the shell of the outside of the sidewall of described content cavity and bioreactor; Described outer cavity volume is separated into liquid storage tank, oxygenate district and following liquid storage tank from top to bottom successively by first dividing plate and second partition; Described oxygenate district internal fixation is equipped with the oxygenator of being made up of around content cavity doughnut, and the described liquid storage tank of going up is communicated with by described doughnut with following liquid storage tank; The inside of the shell of described end cap portions is provided with fluid passage, and described content cavity is communicated with by this fluid passage with last liquid storage tank; On the shell of described bioreactor, be provided with liquid storage tank first liquid inlet and last liquid storage tank pressure compensation opening, be provided with down the liquid storage tank pressure compensation opening, on the lower end of liquid storage tank down is provided with down the liquid storage tank liquid outlet, is described, be equipped with the bacteriological filtration film in liquid storage tank pressure compensation opening and the following liquid storage tank pressure compensation opening respectively at the upper end of last liquid storage tank in the upper end of liquid storage tank down; The described first cavity internal fixation is equipped with the first cell mesh screen, and the cervical region place of described content cavity is installed with the second cell mesh screen, and the content cavity area contents between the described first cell mesh screen and the second cell mesh screen has been received microencapsulated hepatocyte.
Further, the present invention also is provided with content cavity second liquid outlet in the crown center zone of end cap portions, and the upper end of described fluid passage extends to described content cavity second liquid outlet, and the lower end of fluid passage extends to the described liquid storage tank of going up.
Further, content cavity first liquid outlet of the present invention and content cavity second liquid outlet are formed by the conjoint outlet bifurcated.
Compared with prior art, the invention has the beneficial effects as follows: at former artificial liver microcapsule suspension type fluidized bed type bioreactor (China Patent No.: the ZL200710070279.0) space characteristic of funnel type, increase under the unconspicuous prerequisite not introducing taking up room of peripheral hardware liquid storage tank and oxygenator, reactor, liquid storage tank and oxygenator design are incorporated in the middle of the reactor.Thereby realize that blood plasma (or liquid) circulation perfusion is in reactor, and perfusion rate is not subjected to from treating the flow restriction of the blood plasma of drawing in the subject, promote fully suspend fluidisation, material of microcapsule and exchange fully, also can microencapsulated hepatocyte appropriateness oxygen supply in reactor.The application of bioreactor of the present invention can reduce the usage quantity of equipment in the bioartificial liver system, reduces system's occupation space, is convenient to clinical practice.In addition, the open structure of bioreactor of the present invention can make things convenient for user to add microencapsulated hepatocyte to content cavity.
Description of drawings
Fig. 1 is the perspective view of bioreactor of the present invention;
Fig. 2 is bioreactor end cap portions of the present invention and main part decomposition sketch map;
Fig. 3 is the A-A cutaway view of Fig. 1;
Fig. 4 is the external system supplymentary device of a bioreactor of the present invention sketch map;
Among the figure, 1. content cavity first liquid outlet, 2. content cavity first liquid outlet valve of attaching troops to a unit, 3. content cavity second liquid outlet, 4. content cavity second liquid outlet valve of attaching troops to a unit, 5. the sidewall of first cavity, 6. the shell of end cap portions, 7. first cellular filter, 8. go up liquid storage tank first liquid inlet valve of attaching troops to a unit, 9. go up liquid storage tank first liquid inlet, 10. the sidewall of content cavity, 11. last liquid storage tank, 12. oxygenators, 13. oxygenator gas accesses, 14. following liquid storage tank, 15. the second cell mesh screen, 16. content cavity liquid inlets, 17, the content cavity liquid inlet valve of attaching troops to a unit, the valve 18. second cellular filter, 19. times liquid storage tank liquid outlets, 20. times liquid storage tank liquid outlets are attached troops to a unit, 21. following liquid storage tank pressure compensation opening bacteriological filtration film, the valve 22. following liquid storage tank pressure compensation opening, 23. times liquid storage tank pressure compensation openings are attached troops to a unit, 24. microencapsulated hepatocytes, 25. the sidewall of second cavity, 26. oxygenator gas outlet, 27. content cavity, 28. internal partition joining places, 29. shell joining place, 30. last liquid storage tank pressure compensation opening bacteriological filtration film, liquid storage tank pressure compensation opening on 31., the liquid storage tank pressure compensation opening valve of attaching troops to a unit on 32., 33. the first cell mesh screen, 34. fluid passage, the shell of 35. main parts, 36. end cap portions, 37. first cavity, 38. end cap portions shell lower end screw thread, 39. end cap portions internal partition lower end screw threads, 40. main part shells upper end screw thread, 41. main part internal partition upper end screw thread, 42. main part, 43. second cavitys, 44. treatment targets, 45. first blood pump, 46. second blood pump, 47. plasma separators, 48. 1 kinds of integrated form microcapsule suspension type fluidized bed type bioreactors, 49. prolong pipe, 50. liquid outlet, 51. three-way valves, 52. the 3rd blood pumps, 53. oxygen tank, 54. the immune molecule adsorber, 55. the 4th blood pumps, the shell of 56. bioreactors, 57. first dividing plate, 58. second partition, on 59. liquid storage tank second liquid inlet, 60. doughnuts.
The specific embodiment
As depicted in figs. 1 and 2, usually, the outward appearance of integrated form microcapsule suspension type fluidized bed type bioreactor 48 of the present invention is cylindrical, high 20cm, external diameter 10cm, combined by end cap portions 36 and main part 42, specifically, the shell of the shell of end cap portions 36 and main part 42 is threaded at shell joining place 29 places by end cap portions shell lower end screw thread 38 and main part shell upper end screw thread 40 and forms the complete shell of this reactor 56 jointly.End cap portions 36 is separated out first cavity 37 by its internal partition, and the internal partition of end cap portions 36 is the sidewall 5 of first cavity 37; 42 of main parts are separated out second cavity 43 by its internal partition, and the internal partition of main part 42 is the sidewall 25 of second cavity; Be threaded at internal partition joining place 28 by end cap portions internal partition lower end screw thread 39 and main part internal partition upper end screw thread 41, first cavity 37 and second cavity, the 43 common funnel type content cavity 27 that form, the sidewall 10 in the common constitution content of the internal partition of the internal partition of end cap portions 36 and main part 42 chamber 27, the cervical region of funnel type content cavity 27 are positioned at second cavity, 43 place sections; And cavity volume outside between the inboard of the outside of the sidewall 10 of content cavity 27 and shell of reactor 56, forming.Outer cavity volume is separated into liquid storage tank 11, oxygenate district and following liquid storage tank 14 from top to bottom successively by first dividing plate 57 and second partition 58.Wherein, as shown in Figure 3, oxygenate district internal fixation is equipped with the oxygenator of being made up of around content cavity 27 doughnut 60 12, and last liquid storage tank 11 and following liquid storage tank 14 are communicated with by described doughnut.The crown center zone of the shell of end cap portions 36 is provided with content cavity first liquid outlet 1, and the inboard of content cavity first liquid outlet 1 is fixed with first cellular filter 7.The inside of the shell of end cap portions 36 is provided with fluid passage 34, and content cavity 27 is communicated with by this fluid passage 34 with last liquid storage tank 11.As preferential embodiment of the present invention, the crown center zone of the shell of end cap portions 36 also is provided with content cavity second liquid outlet 3, the upper end of fluid passage 34 extends to the crown center zone of shell of end cap portions until content cavity second liquid outlet 3 places, and content cavity second liquid outlet 3 is the upper end open 3 of fluid passage.As depicted in figs. 1 and 2, content cavity first liquid outlet 1 and content cavity second liquid outlet 3 are preferably formed by the conjoint outlet bifurcated.The lower end of fluid passage 34 extends to liquid storage tank 11, and the lower ending opening of fluid passage 34 is liquid storage tank second liquid inlet 59.Bottom zone line at the shell of main part 42 is provided with content cavity liquid inlet 16, and inboard, content cavity liquid inlet is fixed with second cellular filter 18.On the shell of bioreactor, upper end respectively at last liquid storage tank 11 is provided with liquid storage tank first liquid inlet 9 and last liquid storage tank pressure compensation opening 31, be provided with down liquid storage tank pressure compensation opening 22 in the upper end that descends liquid storage tank, be provided with down liquid storage tank liquid outlet 19 in the lower end that descends liquid storage tank.Last liquid storage tank pressure compensation opening 31 and following liquid storage tank pressure compensation opening 22 inboards are equipped with the bacteriological filtration film.The first cell mesh screen 33 is installed in first cavity, the first cell mesh screen 33 is fixed in the inboard (being the inboard of the internal partition of end cap portions) of the sidewall 5 of first cavity, the cervical region place of content cavity 27 (i.e. the cervical region place of " funnel ") is equipped with the cervical region inboard (being the inboard, internal partition lower end of main part) that the second cell mesh screen, 15, the second cell mesh screens 15 are fixed in second cavity.Content cavity area contents between the first cell mesh screen 33 and the second cell mesh screen 15 is received microencapsulated hepatocyte.Each the liquid gateway and the pressure compensation opening of bioreactor of the present invention are equipped with the valve of attaching troops to a unit.
Integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention is divided into end cap portions 36 and main part 42 two parts, two parts are combined into reactor monolith by tight connection of screw thread, and this open structure can add microencapsulated hepatocyte more easily in the content cavity of reactor.Screw thread between end cap portions 36 and the main part 42 is connected will play sealing function, and can bear big pressure, prevent liquid from content cavity and/or outside cavity volume ooze out.
The integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention intermediary oxygenate of cavity volume district internal fixation outside has oxygenator 12, it is made up of around reactor content cavity 27 doughnut 60 of the permeable watertight of vertical arrangement, general high 5cm, annular wide 1.3cm.First dividing plate 57 is fixed in the upper end of doughnut, and second partition 58 is fixed in the lower end of doughnut, and the material of doughnut can be polyether sulfone or polysulfones.First dividing plate 57 and second partition 58 have through hole, make liquid to enter down liquid storage tank from last liquid storage tank through the inner chamber of doughnut.Oxygen (or mist) can enter in the oxygenator from oxygenator gas access 13 simultaneously, leaves oxygenator from oxygenator gas outlet 26; Oxygen is realized oxygenate by by the motion of court's direction obliquely down with the blood plasma generation convection current of the hollow fiber cavity that flows from top to bottom.By regulating the flow proportional of oxygen and blood plasma, the microencapsulated hepatocyte 24 that can be in the content cavity 27 of reactor provides suitable partial pressure of oxygen.
Integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention is provided with liquid storage tank 11 and following liquid storage tank 14, and its common functional equivalent is in the liquid storage tank of peripheral hardware.Usually, the high 7cm of last liquid storage tank, the wide 1.3cm of base circle, the about 110ml of volume; The high 3.4cm of following liquid storage tank, the about 140ml of volume.Part blood plasma in the reactor content cavity can pass through reactor content cavity second liquid outlet 3, fluid passage 34 successively, go up upward liquid storage tank 11 of liquid storage tank second liquid inlet, 59 inflows, and the blood plasma of treatment target 44 also can enter into liquid storage tank 11 by last liquid storage tank first liquid inlet 9.Liquid in the last liquid storage tank 11 can flow into down liquid storage tank 14 through the hollow fiber cavity of oxygenator, the middle liquid process of following liquid storage tank is liquid storage tank liquid outlet 19 down, can blowback reactor content cavity through prolonging pipe the 49, the 3rd blood pump 52, content cavity liquid inlet 16, thus realize the circulation perfusion of treatment target blood plasma.Because some liquid is the circulation perfusion, so the flow rate of liquid of content cavity liquid inlet 16 can not be subjected to treatment target to draw the restriction of the speed of blood plasma (promptly going up the flow rate of liquid of liquid storage tank first liquid inlet 9), realize suspend the fully abundant exchange of fluidisation and material of microcapsule thereby can strengthen flow velocity.In addition, last liquid storage tank 11 is provided with liquid storage tank pressure compensation opening 31 and inboard last liquid storage tank pressure compensation opening thereof attach troops to a unit valve 32 and last liquid storage tank pressure compensation opening bacteriological filtration film 30; Following liquid storage tank 14 is provided with down liquid storage tank pressure compensation opening 22 and inboard following liquid storage tank pressure compensation opening thereof attach troops to a unit valve 23 and following liquid storage tank pressure compensation opening bacteriological filtration film 21.Each pressure compensation opening leads to ambient atmosphere, and is open as required and close, and can make things convenient for the height of liquid level in inflow, outflow and the adjusting liquid storage tank of liquid.Last liquid storage tank pressure compensation opening bacteriological filtration film 30 and following liquid storage tank pressure compensation opening bacteriological filtration film 21 are the mixed cellulose ester in 0.22 micron in aperture, can stop extraneous antibacterial to enter in the liquid storage tank.
According to principle of hydrodynamics and in conjunction with the characteristics of bioreactor of the present invention, the optimum position of content cavity first liquid outlet of integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention, content cavity second liquid outlet and content cavity liquid inlet is the center of reactor head and bottom enclosure.As depicted in figs. 1 and 2, as preferred implementation of the present invention, content cavity first liquid outlet and content cavity second liquid outlet are formed by the conjoint outlet bifurcated.
The aperture of the first cell screen cloth 33 and the second cell screen cloth 15 is 200 orders, and the aperture of cellular filter 3 and cellular filter 30 is 2.5 microns.The purpose of these devices is filtration cell and possible chip, prevents that it from entering in the treatment target blood circulation, avoids the generation of untoward reaction.
The content cavity of integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention has kept artificial liver, and (China Patent No.: ZL200710070279.0) general characteristics of funnel type is also revised a little with microcapsule suspension type fluidized bed type bioreactor.Usually, the total height of content cavity is 20cm, goes up the top directly for 9cm, the footpath of going to the bottom are 4cm that total measurement (volume) is about 780cm.Can realize microcapsule mitigation parabola sample movement locus and repeatedly fluidisation avoided perfusion dead space and invalid perfusion effectively in the reactor inner chamber.Need to prove that the size of bioreactor of the present invention is not limited to above-mentioned size, its big I zooms in or out according to actual needs.
The shell of integrated form microcapsule suspension type fluidized bed type bioreactor of the present invention and the material of each dividing plate are transparent Merlon, good biocompatibility, and can observe the height of liquid storage tank and inner chamber liquid level easily.
Below further specify the using method of bioreactor of the present invention:
(1) before the use reactor is sterilized.In aseptic super-clean bench or hundred grades of laboratorys, turn on this bioreactor end cap portions, second cavity is opened wide.In second cavity, add microencapsulated hepatocyte, by the 3rd blood pump 52 can with more than liquid through exporting 50 content cavity of discharging bioreactors.End cap portions and main part portion that microencapsulated hepatocyte adds the post-reactor that finishes tighten again.
(2) by last liquid storage tank first liquid inlet 9 usefulness normal saline last liquid storage tank 11, following liquid storage tank 14 and bioreactor content cavity 27 are carried out the liquid preliminary filling, will note the switching of relevant Liquid valve and the switching of pressure compensation opening valve in the implementation process.
(3) by shown in Figure 4, connect each pipeline, pipeline is carried out the liquid preliminary filling with normal saline.Give treatment target a certain amount of normal saline, the blood volume that outflows during with prosthodontic treatment.
(4) after the treatment beginning, the arterial blood of treatment target pumps into plasma separator 47 through first blood pump 45, the blood plasma that is separated enters into liquid storage tank 11 through last liquid storage tank first liquid inlet 9, partially liq in the content cavity can pass through content cavity second liquid outlet 5, fluid passage 34, go up liquid storage tank second liquid inlet 59 simultaneously, and liquid storage tank 11 in the inflow; Flow of liquid in the last liquid storage tank 11 is through the hollow fiber cavity supply oxygen of oxygenator, enter down liquid storage tank 14, after successively through following liquid storage tank liquid outlet 19, prolong pipe 49, reactor content cavity liquid inlet 16, pump in the reactor content cavity by the 3rd blood pump 52, microencapsulated hepatocyte suspension fluidisation in the driving a reaction device content cavity, the blood plasma of treatment target and microencapsulated hepatocyte carry out mass exchange; Part blood plasma flows out through content cavity first liquid outlet 1 then, mixes with direct blood by plasma separator 47 by immune molecule adsorber 54 backs, in the defeated ex vivo of vein end; Other has part blood plasma to flow out through content cavity second liquid outlet 3, through fluid passage 34, last liquid storage tank second liquid inlet 59, flows back to liquid storage tank 11 once more, thereby makes part plasma circulation perfusion in reactor.For protect the direct circulation perfusion continue carry out, need be controlled the flow that passes in and out each liquid gateway by the pump speed of regulating blood pump, also need the switching of pressure compensation opening is controlled.In general, when treatment was carried out, the flow velocity of content cavity first liquid outlet 1 equaled the flow velocity of liquid storage tank first liquid inlet 9, and the flow velocity of content cavity liquid inlet 16 equals content cavity first liquid outlet 1 and content second liquid outlet 3 flow velocity sums; Attach troops to a unit valve 22 of following liquid storage tank pressure compensation opening keeps closed conditions, and the last liquid storage tank pressure compensation opening valve 31 of attaching troops to a unit is in open state, is beneficial to liquid and passes through oxygenator.Oxygen (or mist) in the oxygen tank 53 enters in the oxygenator from oxygenator gas access 13 by pipeline simultaneously, leave oxygenator from oxygenator gas outlet 26, move upward from declivity, with from top to bottom stream doughnut in blood plasma generation convection current and realize oxygenate, the flow proportional of adjustments of gas and liquid, the microencapsulated hepatocyte that can be in the reactor inner chamber provides suitable partial pressure of oxygen.
(5) treatment closes to an end, when entering blood plasma and being fed back into intravital stage of treatment target, stop to draw blood from the treatment target arterial end, close the attach troops to a unit valve of valve 4 and last liquid storage tank first liquid inlet 9 of content cavity second liquid outlet, make liquid storage tank pressure compensation opening 31 keep open, make down liquid storage tank pressure compensation opening 22 keep closing, reduce the pump speed of the 3rd blood pump 52, make that the liquid in the upper and lower liquid storage tank returns in the treatment target body through reactor content cavity, content cavity first liquid outlet; After the liquid emptying of upper and lower liquid storage tank, can adjust the open direction of pipeline configuration, three-way valve 51, the wriggling direction of the 3rd blood pump 52, can be so that the liquid in the reactor content cavity returns in the treatment target body through content cavity liquid inlet 16 and prolongation pipeline thereof.
Claims (3)
1. integrated form microcapsule suspension type fluidized bed type bioreactor, it is characterized in that: it is made up of end cap portions (36) and main part (42), be provided with first cavity (37) in the described end cap portions, be provided with second cavity (43) in the described main part, the upper end of described second cavity is threaded with the lower end of first cavity and forms funnel type content cavity (27) jointly; Be provided with content cavity first liquid outlet (1) in the crown center zone of end cap portions, the inboard of content cavity first liquid outlet is fixed with first cellular filter (7); Be provided with content cavity liquid inlet (16) at the bottom of main part zone line, the inboard of described content cavity liquid inlet is fixed with second cellular filter (18); The lower end of the shell of described end cap portions is threaded with the upper end of the shell of described main part and forms the shell (56) of described bioreactor jointly, and cavity volume outside forming between the inboard of the shell (56) of the outside of the sidewall (10) of described content cavity and bioreactor; Described outer cavity volume is separated into liquid storage tank (11), oxygenate district and following liquid storage tank (14) from top to bottom successively by first dividing plate (57) and second partition (58); Described oxygenate district internal fixation is equipped with the oxygenator of being made up of around content cavity doughnut (12), and the described liquid storage tank of going up is communicated with by described doughnut with following liquid storage tank; The inside of the shell of described end cap portions is provided with fluid passage (34), and described content cavity is communicated with by this fluid passage with last liquid storage tank; On the shell of described bioreactor, be provided with liquid storage tank first liquid inlet (9) and last liquid storage tank pressure compensation opening (31), be provided with down liquid storage tank pressure compensation opening (22), on the lower end of liquid storage tank down is provided with down liquid storage tank liquid outlet (19), is described, be equipped with the bacteriological filtration film in liquid storage tank pressure compensation opening and the following liquid storage tank pressure compensation opening respectively at the upper end of last liquid storage tank in the upper end of liquid storage tank down; The described first cavity internal fixation is equipped with the first cell mesh screen (33), and the cervical region place of described content cavity is installed with the second cell mesh screen (15), and the content cavity area contents between the described first cell mesh screen and the second cell mesh screen has been received microencapsulated hepatocyte.
2. integrated form microcapsule suspension type fluidized bed type bioreactor according to claim 1, it is characterized in that: also be provided with content cavity second liquid outlet (3) in the crown center zone of end cap portions, the upper end of described fluid passage extends to described content cavity second liquid outlet (3) and locates, and the lower end of fluid passage extends to the described liquid storage tank of going up.
3. integrated form microcapsule suspension type fluidized bed type bioreactor according to claim 2 is characterized in that: described content cavity first liquid outlet and content cavity second liquid outlet are formed by the conjoint outlet bifurcated.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
| CN112826997A (en) * | 2020-12-31 | 2021-05-25 | 广东乾晖生物科技有限公司 | Bioartificial liver support system based on cell contact bioreactor |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992007615A1 (en) * | 1990-10-29 | 1992-05-14 | Regents Of The University Of Minnesota | A bioartificial liver |
| WO1999018189A1 (en) * | 1997-10-08 | 1999-04-15 | Unisyn Technologies, Inc. | Method of culturing cells in a basket-type bioreactor |
| CN101129277A (en) * | 2007-08-17 | 2008-02-27 | 浙江大学 | Filling bracket perfusion type bioreactor for artificial liver |
| CN101129276A (en) * | 2007-08-13 | 2008-02-27 | 浙江大学 | Microcapsule suspension type fluidized bed type bioreactor for artificial liver |
| CN101732770A (en) * | 2009-12-14 | 2010-06-16 | 浙江大学 | Dual-cavity liquid storage tank for biological artificial liver support system |
| CN202096521U (en) * | 2011-05-05 | 2012-01-04 | 浙江大学 | Integrated type micro-sac suspension type fluidized bed bio-reactor |
-
2011
- 2011-05-05 CN CN 201110114838 patent/CN102210892B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992007615A1 (en) * | 1990-10-29 | 1992-05-14 | Regents Of The University Of Minnesota | A bioartificial liver |
| WO1999018189A1 (en) * | 1997-10-08 | 1999-04-15 | Unisyn Technologies, Inc. | Method of culturing cells in a basket-type bioreactor |
| CN101129276A (en) * | 2007-08-13 | 2008-02-27 | 浙江大学 | Microcapsule suspension type fluidized bed type bioreactor for artificial liver |
| CN101129277A (en) * | 2007-08-17 | 2008-02-27 | 浙江大学 | Filling bracket perfusion type bioreactor for artificial liver |
| CN101732770A (en) * | 2009-12-14 | 2010-06-16 | 浙江大学 | Dual-cavity liquid storage tank for biological artificial liver support system |
| CN202096521U (en) * | 2011-05-05 | 2012-01-04 | 浙江大学 | Integrated type micro-sac suspension type fluidized bed bio-reactor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104353142A (en) * | 2014-09-30 | 2015-02-18 | 南京比瑞生物科技有限公司 | Biological artificial liver reactor |
| CN112826997A (en) * | 2020-12-31 | 2021-05-25 | 广东乾晖生物科技有限公司 | Bioartificial liver support system based on cell contact bioreactor |
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| CN102210892B (en) | 2012-12-19 |
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