CN208517433U - A kind of bioreactor - Google Patents
A kind of bioreactor Download PDFInfo
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- CN208517433U CN208517433U CN201820205386.3U CN201820205386U CN208517433U CN 208517433 U CN208517433 U CN 208517433U CN 201820205386 U CN201820205386 U CN 201820205386U CN 208517433 U CN208517433 U CN 208517433U
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Abstract
The utility model provides a kind of bioreactor, including shell (1), top cover (2) and multiple tissue culture plates (6), the shell (1) has open upper end and closed lower end, and wherein lower end is provided with and the import (3) of shell (1) internal fluid communication；The top cover (2) covers the open upper end of shell (1) and is provided with and the outlet (4) of shell (1) internal fluid communication；The multiple tissue culture plate (6) is separated from each other and is set in parallel internal in shell (1), each tissue culture plate (6) is provided with centrally located through-hole (51) and multiple apertures (61) around the through-hole (51) distribution, and through-hole (51) the formation central passage (5) aligned with each other of multiple tissue culture plates.The bioreactor of the utility model is more advantageous to blood plasma to be clean and spreads to tissue culture plate surrounding, carries out sufficient mass exchange with cell.
Description
Technical field
The present invention relates to medical instrument, especially a kind of bioreactor.
Background technique
Biological blood purification system is the Artificial Liver Support System closest with normal liver, by by hepatocyte cultures
Technology is combined with blood purification technology, can than more fully substitute liver detoxification, biosynthesis and secretion metabolism etc. functions,
It is expected to become the most innovative remedy measures with challenge of heavy type hepatitis, hepatic failure patients.
The basic principle of biological blood purification system is that the liver cell of in vitro culture proliferation is placed in special biological respinse
It is outer using hepatocytes secrete endogenous active substance and conversion by carrying out mass exchange and biological effect with liver cell in device
Source property toxin and play biological blood purification effect, wherein endogenous active substance includes various albumen, metabolic enzyme and activity
Factor etc..Bioreactor and liver cell are the cores of biological blood purification system, and performance is directly related to artificial liver
The efficiency and effect of support.
It studies at present and the bioreactor of application is mainly include the following types: (1) hollow-fiber bioreactor: hollow fibre
Dimension reactor has inner cavity and exocoel, and liver cell is often attached to the exocoel of doughnut, is selected according to the cell of separate sources
The biomembrane of suitable molecular cut off avoids that immune response caused by heterogenous cell product occurs, but liver cell is this
It is unevenly distributed in bioreactor, cell viability is easily caused to decline.(2) plate single layer bioreactor: being that cell seeding exists
It is cultivated on plate, its advantage is that cell distribution is uniform, microenvironment is consistent, but surface to volume ratio declines.(3) be perfused bed or
Bracket bioreactor: the bioreactor is planted in liver cell on perfusion bed or bracket, its advantage is that direct with cell
Contact, and the transhipment of substance is increased, also promote the formation of three-dimensional structure, while being also easy to expand cell-volume；The disadvantage is that
Perfusion is uneven, easily blocks.(4) be coated with suspended biological reactor: the bioreactor is to wrap up liver cell with material, is made
Then porous micro-capsule is irrigated culture.Its advantage is that all cells have identical microenvironment, there is the sky of a large amount of cell culture
Between, reduce the generation of immune response；The disadvantage is that cell stability is poor, mass exchange ability is limited.
Utility model content
In order to solve the above-mentioned technical problem, the present invention proposes a kind of anti-for the new bio in biological blood purification system
Answer device.
A kind of bioreactor, including shell, top cover and multiple tissue culture plates, in which:
The shell has open upper end and closed lower end, and wherein lower end is provided with and enclosure interior fluid communication
Import；
The top cover covers the open upper end of shell and is provided with the outlet being in fluid communication with enclosure interior；
The multiple tissue culture plate is separated from each other and is set in parallel inside housings, each tissue culture plate setting
The multiple apertures for having centrally located through-hole and being distributed around the through-hole, and the through-hole of multiple tissue culture plates is right each other
Standard forms channel.
Preferably, in bioreactor provided by the invention, near the through-hole envelope of the top cell culture plate of top cover
It closes, thus the upper end of sealed passage.
Preferably, in bioreactor provided by the invention, the through-hole has in the side of the tissue culture plate
First end, the surrounding of first end are provided with annular installation band, and annular installation takes setting from limit base of the annular installation with protrusion
Seat limits the buckle being arranged on pedestal from limit base projection；The through-hole has the in the other side of the tissue culture plate
Two ends, the surrounding of second end are provided with circular base, recessed buckle slot are provided on circular base.
In addition, in bioreactor provided by the invention, the buckle on the tissue culture plate is arranged in adjacent another
In buckle slot on one tissue culture plate, so that multiple tissue culture plates is separated from each other inside housings and connect in parallel
It is connected together.
By being as above arranged, in bioreactor of the invention, multiple tissue culture plates can pass through the center
Each component of through-hole surrounding setting is connected to each other, and is thus stacked inside housings, and multiple tissue culture plates is logical
Hole formation channel aligned with each other.
Preferably, in bioreactor provided by the invention, the limit pedestal and card of side on the tissue culture plate
Button with the buckle slot of the other side is that quantity is identical multiple, and multiple limit pedestals it is annular install take it is evenly spaced from one another
Distribution is opened, and correspondingly, the distribution evenly spaced from each other on circular base of multiple buckle slots.
In addition, the limit pedestal on tissue culture plate and the circular base fitting on another adjacent tissue culture plate.
Preferably, circular base is surrounded on tissue culture plate, is additionally provided with multiple notches.Notch may be used as liver cell
Suspension or blood plasma to be clean enter the channel on culture plate.Notch is, for example, the slit for surrounding circular base.
Preferably, in bioreactor provided by the invention, multiple apertures of a tissue culture plate with it is adjacent another
Multiple apertures of one tissue culture plate are respectively aligned to form multiple peripheral channels.
By being as above arranged, in bioreactor of the invention, multiple tissue culture plates are stacked inside housings, by every
Through-hole at a tissue culture plate center forms channel, and channel extends along the vertical direction of bioreactor, but thin in top layer
It is closed at born of the same parents' culture plate.In addition, channel can be optionally vertically aligned with export and import.By the outer of keyhole formation
Zhou Tongdao extends along the vertical direction of bioreactor.Import, outlet, channel and peripheral channel are in fluid communication with each other.
Preferably, in bioreactor provided by the invention, the through-hole of each tissue culture plate is circle, the multiple
Aperture is relative to through-hole radial distribution on tissue culture plate, and multiple apertures are spaced apart each other with same distance, and formation is enclosed
Around one or more rings of through-hole.
Preferably, the tissue culture plate and the aperture are respectively circle.
Preferably, closest to the radius of the distance between the aperture of through-hole and through-hole (between the center of circle) and tissue culture plate
Than for 1:2~3, preferably 1:2.7.
Preferably, the ratio of the diameter of the diameter and through-hole of the aperture is 1:3~5, preferably 1:4；
Preferably, the ratio of the diameter of the diameter and tissue culture plate of the aperture is 1:80~100, preferably 1:90.7；
Preferably, the ratio of the diameter of the diameter and tissue culture plate of the through-hole is 1:20~30, preferably 1:22.7.
Specific embodiment according to the present invention, shell are cylindrical body, inside be stacked along the vertical direction 66 with a thickness of
The tissue culture plate of 1mm is linked together by 4 buckles of through-hole two sides and 4 buckle slots between each tissue culture plate,
Largest interval between flanking cell culture plate is 1mm；In addition, the diameter of each tissue culture plate is 136mm, the diameter of through-hole
For 6mm, the diameter of aperture is 1.5mm, is 25mm closest to the distance between the aperture of through-hole and through-hole, between adjacent apertures
Distance be 10mm；There are 112 apertures on each tissue culture plate.
Bioreactor in biological blood purification system is by the way that cultured liver cell is anti-to biology is entered in advance in it
Answer the blood plasma of device to play catharsis, the blood plasma usually from patients such as heavy type hepatitis, hepatic failures, to the blood of the patient into
It is obtained after row separation, the blood plasma after the catharsis of liver cell will be circulated back to patient's body.Compared with the existing technology, originally
The bioreactor of invention has the following characteristics that
First, the lower end of shell is arranged in import by bioreactor of the invention, so that blood plasma to be clean is from shell
Lower end enters inside reactor, while closing near the through-hole of the top cell culture plate of top cover, thus form from lower and
Upper and top closure blood plasma channel.It was found that being arranged in this way, the blood plasma to be clean flowed into from lower end import will be at top
Exit is obstructed, and can only ensure that cell by the gap between flanking cell culture plate towards culture board ends lateral flow
The liquid flowing of sheet separation is cultivated, shearing force is minimum, is conducive to convective exchange.
Second, be not directly anchored in bioreactor of the invention, between tissue culture plate in bioreactor or
In any part in it, but buckle and buckle slot are set in the through-hole surrounding of tissue culture plate, pass through buckle and buckle slot
Cooperation multiple tissue culture plates are connected and fixed to together.This set makes the installation of tissue culture plate more flexible,
And the quantity of bioreactor inner cell culture plate can be easily adjusted, and then adjust the actually active work of bioreactor
The effective exchange area of area, cell between carrying capacity, cell and the blood plasma to be clean on tissue culture plate；It reduces simultaneously simultaneously
The component of bioreactor is simplified, manufacturing cost is reduced.
Third, on the tissue culture plate of bioreactor of the present invention, by aperture be located in at a certain distance from through-hole
Except or, and radially distributed with the radial direction relative to through-hole；In other words, multiple aperture opposing through-bores, which form, encloses
Around the pattern of multiple rings of through-hole, and the ring near through-hole is increased using through-hole as the radius in the center of circle.It is arranged in this way, carefully
Liquid between born of the same parents' culture plate is easier to flow to both ends, is conducive to the convective exchange of blood plasma and liver cell to be clean.
Detailed description of the invention
Hereinafter, carrying out the embodiment that the present invention will be described in detail in conjunction with attached drawing, in which:
Fig. 1 is inside bioreactor structural schematic diagram.
Fig. 2 is bioreactor external structure schematic diagram.
Fig. 3 is tissue culture plate schematic diagram.
Fig. 4 is tissue culture plate side schematic diagram.
Fig. 5 is tissue culture plate other side schematic diagram.
Specific embodiment
The present invention is described below with reference to specific embodiments.It will be appreciated by those skilled in the art that these embodiments are only
For illustrating the present invention, do not limit the scope of the invention in any way.
Experimental method in following embodiments is unless otherwise specified conventional method.Medicine as used in the following examples
Material raw material, reagent material etc. are commercially available products unless otherwise specified.
Embodiment 1The design of bioreactor of the invention
(1) entrance location, laminate spacing and flow field analysis
The top layer in bioreactor and the through-hole at bottom tissue culture plate center are closed respectively, do not allow liquid direct
It flows through, while tissue culture plate is arranged to two kinds of spacing of 0.5mm and 2mm respectively, investigate the mobility status of liquid.
(1) bottom culture plate through-hole closing VS top layer culture plate through-hole closing
From the point of view of liquid mobility status, after the through-hole closing of bottom tissue culture plate, the liquid that upper end import flows into is most
Lower layer can force to flow to both ends, and then be further continued for vertical upflow by the aperture on bottom tissue culture plate, this
In the case of be equivalent to the approximate independent liquid of each aperture on bottom tissue culture plate and flow into entrance, provide vertically upward
Flowing, the liquid crossflow between all tissue culture plates in top in this way is dynamic very weak, lacks corresponding convective exchange.
In contrast, when top cell culture plate through-hole closing after, lower end import flow into liquid top exit by
Resistance can only laterally be flowed to both ends by gap layer by layer, ensure that the liquid flowing of cell culture sheet separation, be conducive to convection current friendship
It changes.
Therefore, bioreactor of the invention selection will be closed near the through-hole of the top cell culture plate of top cover, together
When import is set to the lower end of shell.
(2) 0.5mm spacing VS 2.0mm spacing
From the point of view of liquid mobility status, in the case that distance is big between flanking cell culture plate, in cell culture sheet separation
Liquid flows faster, but this can sacrifice the cell bearing capacity of package unit, need the spacing of tissue culture plate in the reactor
An equilibrium relation is established between the cell bearing capacity and cell of reactor and the mass exchange of blood to be clean.
Therefore, bioreactor of the invention selects to set 1.0mm for the spacing between flanking cell culture plate.
(2) aperture position and flow field analysis
On tissue culture plate, multi-turn aperture is set around through-hole, in the case where aperture and other settings all the same,
Investigate the mobility status of liquid when one circle aperture is set less around through-hole.
From the point of view of liquid mobility status, a liquid when collar aperture between tissue culture plate is easier to flow to both ends less, favorably
In convective exchange.
Embodiment 2Bioreactor of the invention
Fig. 1 to Fig. 5 is shown, a kind of bioreactor, including shell 1, top cover 2 and multiple tissue culture plates 6, and shell 1 has
There are open upper end and closed lower end, wherein lower end is provided with the import 3 with 1 internal fluid communication of shell, and top cover 2 covers
The open upper end of shell 1 and it is provided with outlet 4 with 1 internal fluid communication of shell, multiple tissue culture plates 6 are spaced each other
It opens and is set in parallel inside shell 1, each tissue culture plate 6 is provided with centrally located through-hole 51 and around through-hole
Multiple apertures 61 of 51 distributions, and the formation channel 5 aligned with each other of through-hole 51 of multiple tissue culture plates.
Through-hole 51 near the top cell culture plate 62 of top cover 2 is closed, thus the upper end of sealed passage 5.
Through-hole 51 has first end in the side of tissue culture plate 6, and the surrounding of first end is provided with annular installation band 601,
Limit pedestal 602 from 601 protrusion of annular installation band is set on annular installation band 601, limits and is arranged on pedestal 602 from limit base
The buckle 603 of 602 protrusion of seat；Through-hole 51 has second end in the other side of tissue culture plate 6, and the surrounding of second end is provided with
Circular base 605 is provided with recessed buckle slot 606 on circular base 605.
The buckle slot 606 on another adjacent tissue culture plate 6 can be set in buckle 603 on tissue culture plate 6
It is interior, so that multiple tissue culture plates 6 is separated from each other inside shell 1 and is linked together in parallel.
The limit pedestal 602 of side and buckle 603 are identical for quantity as the buckle slot 606 of the other side on tissue culture plate 6
Multiple (being illustrated as 4), and multiple limit pedestals 602 each other annular installation band 601 on evenly-spaced distribution, and
Correspondingly, multiple buckle slots 606 distribution evenly spaced from each other on circular base 605.
Limit pedestal 602 on tissue culture plate 6 and the circular base 605 on another adjacent tissue culture plate 6 paste
It closes.Circular base 605 is surrounded on tissue culture plate 6, is additionally provided with multiple notches 52 (being illustrated as 4).
Multiple apertures 61 of multiple apertures 61 of one tissue culture plate 6 and another adjacent tissue culture plate 6 are distinguished
Alignment forms multiple peripheral channels 7.
By being as above arranged, in bioreactor of the invention, multiple tissue culture plates 6 are stacked in inside shell 1, by
Through-hole 51 at each 6 center of tissue culture plate forms channel 5, and channel 5 extends along the vertical direction of bioreactor, but
It is closed at top cell culture plate 62.In addition, channel 5 can be optionally vertically aligned with outlet 4 and import 3.By
The peripheral channel 7 that aperture 61 is formed extends along the vertical direction of bioreactor.Import 3, outlet 4, channel 5 and peripheral channel 7
It is in fluid communication with each other.
The through-hole 51 of each tissue culture plate 6 is circle, and multiple apertures 61 are on tissue culture plate 6 relative to 51 diameter of through-hole
It is spaced apart to distribution, and each other with same distance, forms the one or more rings (being illustrated as 4) for surrounding through-hole 51.
Also, shell 1 is cylindrical body, and inside has been stacked 66 with a thickness of the tissue culture plate 6 of 1mm, respectively along the vertical direction
It is linked together between a tissue culture plate 6 by the buckle 603 and buckle slot 606 of 51 two sides of through-hole, flanking cell culture plate
Largest interval between 6 is 1mm；In addition, the diameter of each tissue culture plate 6 is 136mm, the diameter of through-hole 51 is 6mm, aperture
61 diameter is 1.5mm, is 25mm closest to the distance between the aperture 61 of through-hole 51 and through-hole 51, between adjacent apertures 61
Distance be 10mm；There are 112 apertures 61 on each tissue culture plate.
Embodiment 3The use of bioreactor of the invention
Using the bioreactor of embodiment 2.
The outlet 4 on top cover 2 is opened, hepatocyte suspension is inputted from the import 3 of 1 lower end of shell, is filled substantially with to suspension whole
After a bioreactor, import 3 is closed, 3-4 hour is stood, makes cell adherent growth in cell culture plate surface.
Bioreactor is connect by the other component of biological blood purification system with human body, blood plasma to be clean is started
Circulation.
Specific description of embodiments of the present invention above is not intended to limit the present invention, and those skilled in the art can be according to this
Invention is variously modified or deforms, and as long as it does not depart from the spirit of the invention, should belong to the model of appended claims of the present invention
It encloses.
Claims (18)
1. a kind of bioreactor, including shell (1), top cover (2) and multiple tissue culture plates (6), which is characterized in that
The shell (1) has open upper end and closed lower end, and wherein lower end is provided with and shell (1) internal fluid communication
Import (3)；
The top cover (2) covers the open upper end of shell (1) and is provided with and the outlet (4) of shell (1) internal fluid communication；
The multiple tissue culture plate (6) is separated from each other and is set in parallel, each tissue culture plate internal in shell (1)
(6) it is provided with centrally located through-hole (51) and multiple apertures (61) around the through-hole (51) distribution, and multiple thin
The through-hole (51) of born of the same parents' culture plate formation central passage (5) aligned with each other.
2. bioreactor according to claim 1, which is characterized in that near the top cell culture plate of top cover (2)
(62) through-hole (51) is closed, thus the upper end of sealed passage (5).
3. bioreactor according to claim 1 or 2, which is characterized in that the through-hole (51) is in the cell culture
The side of plate (6) has first end, and the surrounding of first end is provided with annular installation band (601), is arranged on annular installation band (601)
The limit pedestal (602) of band (601) protrusion is installed from annular, is arranged in limit pedestal (602) from limit pedestal (602) protrusion
It buckles (603)；The through-hole (51) has second end in the other side of the tissue culture plate (6), and the surrounding of second end is arranged
Have circular base (605), recessed buckle slot (606) are provided on circular base (605).
4. bioreactor according to claim 3, which is characterized in that the buckle (603) on the tissue culture plate (6)
It is arranged in the buckle slot (606) on another adjacent tissue culture plate (6) Nei, thus makes multiple tissue culture plates (6) in shell
It is separated from each other and links together in parallel inside body (1).
5. bioreactor according to claim 3, which is characterized in that the limit of side on the tissue culture plate (6)
Pedestal (602) and buckle (603) are identical multiple for quantity with the buckle slot (606) of the other side, and multiple limit pedestals
(602) distribution evenly spaced from each other on band (601) is installed in annular, and correspondingly, multiple buckle slots (606) are in annular base
Distribution evenly spaced from each other on seat (605).
6. bioreactor according to claim 3, which is characterized in that the limit pedestal (602) on tissue culture plate (6)
With circular base (605) fitting on another adjacent tissue culture plate (6).
7. bioreactor according to claim 6, which is characterized in that surround circular base on tissue culture plate (6)
(605), multiple notches (52) are additionally provided with.
8. bioreactor according to claim 1 or 2, which is characterized in that multiple apertures of a tissue culture plate
(61) multiple apertures (61) with another adjacent tissue culture plate are respectively aligned to form multiple peripheral channels (7).
9. bioreactor according to claim 1 or 2, which is characterized in that the through-hole (51) of each tissue culture plate (6)
For circle, the multiple aperture (61) on tissue culture plate (6) relative to through-hole (51) radial distribution, and multiple apertures
(61) it is spaced apart each other with same distance, forms the one or more rings for surrounding through-hole (51).
10. bioreactor according to claim 1 or 2, which is characterized in that the tissue culture plate (6) and described small
Hole (61) is respectively circle.
11. bioreactor according to claim 1 or 2, which is characterized in that closest to through-hole (51) aperture (61) with
The ratio of the distance between through-hole (51) and the radius of tissue culture plate (6) is 1:2~3.
12. bioreactor according to claim 11, which is characterized in that closest to the aperture (61) of through-hole (51) and logical
The ratio of the distance between hole (51) and the radius of tissue culture plate (6) is 1:2.7.
13. bioreactor according to claim 1 or 2, which is characterized in that the diameter and through-hole of the aperture (61)
(51) ratio of diameter is 1:3~5.
14. bioreactor according to claim 13, which is characterized in that the diameter of the aperture (61) and through-hole (51)
Diameter ratio be 1:4.
15. bioreactor according to claim 1 or 2, which is characterized in that the diameter and cell of the aperture (61) are trained
The ratio for supporting the diameter of plate (6) is 1:80~100.
16. bioreactor according to claim 15, which is characterized in that the diameter of the aperture (61) and cell culture
The ratio of the diameter of plate (6) is 1:90.7.
17. bioreactor according to claim 1 or 2, which is characterized in that the diameter and cell of the through-hole (51) are trained
The ratio for supporting the diameter of plate (6) is 1:20~30.
18. bioreactor according to claim 17, which is characterized in that the diameter of the through-hole (51) and cell culture
The ratio of the diameter of plate (6) is 1:22.7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201820205386.3U CN208517433U (en) | 2018-02-06 | 2018-02-06 | A kind of bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201820205386.3U CN208517433U (en) | 2018-02-06 | 2018-02-06 | A kind of bioreactor |
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| Publication Number | Publication Date |
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| CN208517433U true CN208517433U (en) | 2019-02-19 |
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| CN201820205386.3U Active CN208517433U (en) | 2018-02-06 | 2018-02-06 | A kind of bioreactor |
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