CN106267402B - Semi-permeable membrane layer-stepping bioartificial liver monitors on-line and heated at constant temperature integrated system - Google Patents
Semi-permeable membrane layer-stepping bioartificial liver monitors on-line and heated at constant temperature integrated system Download PDFInfo
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- CN106267402B CN106267402B CN201610608802.XA CN201610608802A CN106267402B CN 106267402 B CN106267402 B CN 106267402B CN 201610608802 A CN201610608802 A CN 201610608802A CN 106267402 B CN106267402 B CN 106267402B
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- 239000012528 membrane Substances 0.000 title claims abstract description 95
- 210000004185 liver Anatomy 0.000 title claims abstract description 36
- 239000008280 blood Substances 0.000 claims abstract description 64
- 210000004369 blood Anatomy 0.000 claims abstract description 63
- 210000002381 plasma Anatomy 0.000 claims abstract description 63
- 238000001914 filtration Methods 0.000 claims abstract description 53
- 210000004027 cell Anatomy 0.000 claims abstract description 33
- 238000012544 monitoring process Methods 0.000 claims abstract description 24
- 210000001367 artery Anatomy 0.000 claims abstract description 17
- 238000011084 recovery Methods 0.000 claims abstract description 10
- 238000000926 separation method Methods 0.000 claims description 23
- 239000000835 fiber Substances 0.000 claims description 20
- 239000010410 layer Substances 0.000 claims description 20
- 239000011229 interlayer Substances 0.000 claims description 17
- 238000010438 heat treatment Methods 0.000 claims description 16
- 210000005229 liver cell Anatomy 0.000 claims description 9
- 238000011144 upstream manufacturing Methods 0.000 claims description 8
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 7
- 229960002897 heparin Drugs 0.000 claims description 7
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 230000004888 barrier function Effects 0.000 claims description 6
- 206010058490 Hyperoxia Diseases 0.000 claims description 4
- 230000000222 hyperoxic effect Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000012806 monitoring device Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 210000003462 vein Anatomy 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 16
- 239000000126 substance Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000015556 catabolic process Effects 0.000 abstract description 2
- 238000006731 degradation reaction Methods 0.000 abstract description 2
- 238000013461 design Methods 0.000 abstract description 2
- 230000010412 perfusion Effects 0.000 description 5
- 206010019663 Hepatic failure Diseases 0.000 description 4
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- 208000007903 liver failure Diseases 0.000 description 4
- 231100000835 liver failure Toxicity 0.000 description 4
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 235000012489 doughnuts Nutrition 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
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- 102000001554 Hemoglobins Human genes 0.000 description 1
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- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1621—Constructional aspects thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1698—Blood oxygenators with or without heat-exchangers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
Abstract
The invention discloses semi-permeable membrane layer-stepping bioartificial liver on-line monitorings and heated at constant temperature integrated system, including blood input port, blood pump, artery pot, semi-permeable membrane layering integrated biological reactor, venous chambers and the blood recovery mouth that sequence is connected；It includes cavity that semi-permeable membrane, which is layered integrated biological reactor, be arranged cavity side plasma separator and bioreactor in the cavity other side is set；Plasma separator and bioreactor are spaced apart by separating semi-permeable membrane；Being horizontally disposed in bioreactor has multiple filtration semi-permeable membrane.The beneficial effects of the invention are as follows：Design is more simple and practical；It is come into full contact between cell and blood plasma, is conducive to the exchange efficiency for improving two substances, degradation blood plasma effect is more preferable；Cell parking space is increased, useful load is increased.
Description
Technical field
The invention belongs to bioartificial liver's technical fields more particularly to a kind of semi-permeable membrane layer-stepping bioartificial liver to supervise online
It surveys and heated at constant temperature integrated system.
Background technology
China liver failure patient populations are huge, seek effective treatment means of new hepatic failure and become urgently to be resolved hurrily
Problem.Bioartificial liver system can maintain patients ' lives, and the chance for waiting for liver transfer operation chance or patient itself liver to restore, is recent
The hot spot of research and development.Biological artificial liver support system, mainly using the cell mass with liver metabolism function, to hepatic failure patients
Blood is purified, and realizes the function that Vitro hepatic ramus splanchnicus is held, and for liver regeneration or liver transplant is waited for win the quality time, had
There is important clinical application value.
Bioreactor is the core of bioartificial liver, and performance is directly related to support and the treatment effect of artificial liver
Fruit.A kind of bioreactor studied and be most widely used at present is hollow fiber type reactor, the structure one of the reactor
As be made of the doughnut in cylindrical reactor shell and filling shell, doughnut bunchy arrangement, in hollow fiber walls
It can prevent heterologous protein from entering human body its advantage is that foreign protei can be isolated with the aperture that can be used for exchanging and cause allergy
Reaction, while preventing lethal effect of the preexisting antibody in human body for heterogenous cell antigen to cell.But such reactor
There are problems that, such as limited volume, loading cells amount is small, and culture solution or blood and liver cell exchange area are limited, in addition, carefully
Fiber fenestra is easily blocked when intracellular growth, further influences the mass exchange inside and outside film, is unfavorable for the function and vigor of liver cell
Permanently effective maintenance and effectively treatment.And existing bioartificial liver's reactor is heated just with heat booster at present, and
Heated at constant temperature cannot be carried out to bioartificial liver's reactor, heating is unstable, influences the efficiency of bioartificial liver's reactor.
Ideal bioartificial liver system should have following characteristics：It is simple system, easy to operate；It is suitable to be provided for cell
Metabolism environment ensures cell activity；The cell distribution of perfusion is uniform, and loading cells amount is big, cell can be come into full contact with blood plasma into
Row mass exchange.
Invention content
The purpose of the present invention overcomes existing bioartificial liver system complicated, cumbersome, the corresponding biology of system
The problems such as reactor volume is limited, loading cells amount is small, blood plasma and liver cell exchange area are limited, cell distribution is uneven, carries
For a kind of semi-permeable membrane layer-stepping bioartificial liver on-line monitoring and heated at constant temperature integrated system, it has simple system, operation letter
Just, increase loading cells amount, heated at constant temperature, the features such as improving the exchange efficiency and uniformity coefficient of substance.
To achieve the above object, the semi-permeable membrane layer-stepping bioartificial liver on-line monitoring and heated at constant temperature designed by the present invention
Integrated system, including blood input port, blood pump, artery pot, semi-permeable membrane that sequence is connected are layered integrated biological reactor, vein
Pot and blood recovery mouth；
Semi-permeable membrane layering integrated biological reactor includes cavity, be arranged cavity side plasma separator and set
Set the bioreactor in the cavity other side；Plasma separator and bioreactor are spaced apart by separating semi-permeable membrane；
Blood entry port is offered on the cavity of plasma separator side and haemocyte exports, in plasma separator
Portion is filled with more hollow fibre filaments；Described hollow fibre filament one end is connected to blood entry port, and the other end connects with haemocyte outlet
It is logical；
Plasma outlet port is offered at the top of the cavity of the other side where bioreactor, level is set in bioreactor
Be equipped with multiple filtration semi-permeable membrane, the filtering semi-permeable membrane be used to obstruct free cell pass through and two adjacent filtering semi-permeable membranes with
The side wall of bioreactor forms an independent filtering layer space together, and each the corresponding cavity in independent filtering layer space is equipped with
Liver cell perfusing hole；The filtering semi-permeable membrane of top layer is detached with holding at the top of bioreactor；Undermost filtering semi-permeable membrane with
Interlayer is formed on bioreactor bottom, in the interlayer filled with permeable fiber silk and the corresponding cavity of the interlayer be equipped with into
Gas port, the air inlet are only connected to permeable fiber silk；
The plasma separator pumps connecting tube by the separation equipped with separation pump with bioreactor and is connected to the two；It is described
The arrival end of separation pump connecting tube is located at the side wall lower ends of the cavity of the plasma separator side, and outlet end is located at described
The bottom of the cavity of bioreactor side；
The blood entry port is connected with the outlet of artery pot, the plasma outlet port and haemocyte export together with the vein
The entrance of pot is connected；
The integrated system is additionally provided with pipeline heating device.
Further, the filtering semi-permeable membrane and separation semi-permeable membrane are flat membrane element, the week of the flat membrane element
Side is bonded fixation with cavity；The aperture of the filtering semi-permeable membrane pumps the direction of connecting tube outlet end one by one according to far from the separation
Successively decrease.
The advantageous effect of above-mentioned further scheme is：Successively decreased one by one by using the surface pores diameter for filtering semi-permeable membrane
Mode be arranged, can not only prevent filtering semi-permeable membrane block, also can guarantee that plasma flow rate is uniform and stable.
Still further, being equipped with the barrier semi-permeable membrane for preventing cell permeable in the plasma outlet port.
The advantageous effect of above-mentioned further scheme is：By obstructing the effect of semi-permeable membrane, it is avoided that cell or cellular products
Into blood, barrier macromolecular substances penetrate, and prevent allergy.
Further, alternate outlets and pressure sensor are additionally provided on the corresponding cavity in the filtering layer space.
The advantageous effect of above-mentioned further scheme is：It is stifled to have detected whether that filtering semi-permeable membrane occurs by pressure sensor
Plug connects two alternate outlets by connecting tube when a jam does occur, is caused in cycle when preventing filtering semi-permeable membrane from blocking
It is disconnected, so that blood plasma is passed through connecting tube and enter next filtering layer space blocked without filtering semi-permeable membrane, treatment is made to continue.
Further, the blood entry port offers hyperoxia water inlet；It is further opened with blood plasma on the plasma separator
The spare adding mouth of separator；The corresponding cavity of the interlayer is equipped with gas outlet/reserved opening.
Still further, the integrated system includes the biomonioring device for continuously monitoring biochemical indicator on-line, institute
It includes that the upstream supervised TT＆C system, signal feedback system and connect with the prison TT＆C system electric signal is managed to state biomonioring device
Biochemical indicator detecting head is managed in biochemical indicator detecting head and downstream；The upstream reason biochemical indicator detecting head is inputted set on the blood
At mouthful, the downstream reason biochemical indicator detecting head is set at the blood recovery mouth.
Optionally, on the artery pot, on venous chambers addition drug, is respectively provided between blood pump and blood input port
Or the branch pipe of liquid；The heparin branch pipe for injecting heparin is equipped between the blood pump and artery pot.
Preferably, it is additionally provided between the venous chambers and the blood recovery mouth for monitoring in pipeline whether have air
Air monitoring device.
Further, the pipeline heating device is water-bath, and semi-permeable membrane layering integrated biological reactor is placed in water
In bath, the water-bath uses external hanging type water-bath.
Preferably, the integrated system further includes multiple pressure-detecting devices, be respectively arranged on artery pot, on venous chambers,
In separation pump connecting tube, between blood input port and blood pump.
The beneficial effects of the invention are as follows：
1, by improving the structure of bioartificial liver's reactor in existing bioartificial liver system, plasma separator is anti-with biology
Device is answered to splice or directly plasma separator is placed in bioreactor, design is more simple and practical；
2, it is passed through high-oxygen water to starch with oxygenated blood while ensureing that cell supplies oxygen, be further provided for by the effect of permeable fiber silk
Enough oxygen can provide suitable for metabolism environment for cell, ensure cell activity, keep cell culture better, be conducive to thin
The maintenance of born of the same parents' function improves therapeutic effect；
3, the blood plasma detached enters bioreactor by separation pump connecting tube, after interlayer, then is successively set through spacing
The filtering semi-permeable membrane set carries out mass exchange with the cell in filtering layer space, and blood plasma can be made to remain stable uniform in this way
Flow velocity comes into full contact between cell and blood plasma, is conducive to the exchange efficiency for improving two substances, and degradation blood plasma effect is more preferable；
4, cell parking space is increased, useful load is increased；
5, the risk that cell enters with blood plasma human body is reduced by the effect filtered semi-permeable membrane, obstruct semi-permeable membrane；
6, filtering semi-permeable membrane is arranged using multilayer, and the use effect of cell is improved for bioreactor in parallel
Rate makes therapeutic effect perform to most preferably；
7, passing through the effect of pipeline heating device so that the cell in bioreactor can carry out constant temperature water bath heating,
Homogeneous heating, thermal-stable are good；And pipeline heating device uses external hanging type, saves space so that system structure is simple；
8, pass through the effect of biomonioring device so that system can carry out the pressure of biochemical indicator, blood plasma or blood
On-line monitoring.
Description of the drawings
Fig. 1 is the structural representation of semi-permeable membrane layer-stepping bioartificial liver of the present invention on-line monitoring and heated at constant temperature integrated system
Figure.
Fig. 2 is the structural schematic diagram of the semi-permeable membrane layering integrated biological reactor in Fig. 1.
Fig. 3 is the dimensional structure diagram of the pipeline heating device in Fig. 1.
Fig. 4 is the schematic cross-sectional view of Fig. 3.
In figure, semi-permeable membrane is layered integrated biological reactor 1, plasma separator 1.1, bioreactor 1.2, cavity 2, divides
Every semi-permeable membrane 3, blood entry port 4, haemocyte outlet 5, hollow fibre filament 6, plasma outlet port 7, filtering semi-permeable membrane 8, liver cell perfusion
Mouthfuls 9, filtering layer space 10, blood input port 11, blood pump 12, artery pot 13, pipeline heating device 14, holder 14.1, venous chambers 15,
Blood recovery mouth 16, barrier semi-permeable membrane 17, alternate outlets 18, pressure sensor 19, separation pump connecting tube 20, hyperoxia water inlet
21, the spare adding mouth 23 of permeable fiber silk 22, plasma separator, separation pump 24, biomonioring device 25, prison TT＆C system
25.1, signal feedback system 25.2, upstream reason biochemical indicator detecting head 25.3, downstream reason biochemical indicator detecting head 25.4, branch pipe
26, heparin branch pipe 27, air monitoring device 28, pressure-detecting device 29, air inlet 30, gas outlet/reserved opening 31, interlayer 32,
Sealed support plate 33.
Specific implementation mode
Below in conjunction with the drawings and specific embodiments, the present invention is described in further detail.
Semi-permeable membrane layer-stepping bioartificial liver on-line monitoring as shown in figures 1-4 and heated at constant temperature integrated system, including it is suitable
The connected blood input port 11 of sequence, blood pump 12, artery pot 13, semi-permeable membrane layering integrated biological reactor 1, venous chambers 15 and blood
Liquid feeds back mouth 16；
Semi-permeable membrane be layered integrated biological reactor 1 include cavity 2, be arranged 2 side of cavity plasma separator 1.1 and
Bioreactor 1.2 in 2 other side of cavity is set；Plasma separator 1.1 and bioreactor 1.2 are by separating semi-permeable membrane 3
It is spaced apart；
Blood entry port 4 and haemocyte outlet 5, blood plasma point are offered on the cavity 2 of 1.1 side of plasma separator
It is filled with more hollow fibre filaments 6 from 1.1 inside of device；6 one end of hollow fibre filament is connected to blood entry port 4, and the other end is thin with blood
5 connection of born of the same parents outlet；
Plasma outlet port 7, bioreactor 1.2 are offered positioned at the top of the cavity 2 of the 1.2 place other side of bioreactor
It is interior it is horizontally disposed have a multiple filtration semi-permeable membrane 8, filtering semi-permeable membrane 8 is used to obstruct free cell and passes through and adjacent two filterings half
Permeable membrane 8 forms an independent filtering layer space 10 together with the side wall of bioreactor 1.2, and each independent filtering layer space 10 is right
The cavity 2 answered is equipped with liver cell perfusing hole 9；The filtering semi-permeable membrane 8 of top layer keeps detaching with 1.2 top of bioreactor；
Interlayer 32 formed on undermost filtering semi-permeable membrane 8 and 1.2 bottom of bioreactor, in interlayer 32 filled with permeable fiber silk 22 and
32 corresponding cavity 2 of interlayer is equipped with air inlet 30, and air inlet 30 is only connected to permeable fiber silk 22；
Plasma separator 1.1 and bioreactor 1.2 pump connecting tube 20 by the separation equipped with separation pump 24 and connect the two
It is logical；The arrival end of separation pump connecting tube 20 is located at the side wall lower ends of the cavity 2 of 1.1 side of plasma separator, outlet end position
In the bottom of the cavity 2 of 1.2 side of bioreactor；
Blood entry port 4 is connected with the outlet of artery pot 13, plasma outlet port 7 and haemocyte outlet 5 together with venous chambers 15
Entrance is connected；
Integrated system is additionally provided with pipeline heating device 14.
Filtering semi-permeable membrane 8 and separation semi-permeable membrane 3 are flat membrane element, and the periphery of flat membrane element is bonded admittedly with cavity 2
It is fixed；Successively decrease one by one according to the direction for pumping 20 outlet end of connecting tube far from separation in the aperture for filtering semi-permeable membrane 8.It is semi-transparent by that will filter
The surface pores diameter of film 8 is arranged by the way of successively decreasing one by one, can not only prevent filtering semi-permeable membrane 8 from blocking, also can
Ensure that plasma flow rate is uniform and stable.
The barrier semi-permeable membrane 17 for preventing cell permeable is equipped in plasma outlet port 7.By obstructing the effect of semi-permeable membrane 17, can keep away
Exempt from cell or cellular products enter blood, barrier macromolecular substances penetrate, and prevent allergy.
It is additionally provided with alternate outlets 18 and pressure sensor 19 on 10 corresponding cavity 2 of filtering layer space.Pass through pressure sensor
19 detected whether filtering semi-permeable membrane 8 block, when a jam does occur, by connecting tube (not shown) connection two it is spare go out
Mouthful, cycle interruption is caused when preventing filtering semi-permeable membrane 8 from blocking, so that blood plasma is passed through connecting tube and enters next no filtering half
Permeable membrane blocks 8 filtering layer space 10, and treatment is made to continue.
Hyperoxia water inlet 21 is offered at blood entry port 4；Be further opened on plasma separator 1.1 plasma separator it is spare plus
Sample mouth 23；32 corresponding cavity 2 of interlayer is equipped with gas outlet/reserved opening 31.
Integrated system includes the biomonioring device 25 for continuously monitoring biochemical indicator on-line, and biomonioring device 25 wraps
Include prison TT＆C system 25.1, signal feedback system 25.2 and the upstream reason biochemical indicator being connect with prison 25.1 electric signal of TT＆C system
Detecting head 25.3 and downstream reason biochemical indicator detecting head 25.4；It manages biochemical indicator detecting head 25.3 and is set to blood input port 11 in upstream
Place, downstream are managed biochemical indicator detecting head 25.4 and are set at blood recovery mouth 16.
Be respectively provided on artery pot 13, on venous chambers 15, between blood pump 12 and blood input port 11 addition drug or
The branch pipe 26 of liquid；The heparin branch pipe 27 for injecting heparin is equipped between blood pump 12 and artery pot 13.
Whether be additionally provided between venous chambers 15 and blood recovery mouth 16 has the air monitering of air to fill for monitoring in pipeline
Set 28.
Pipeline heating device 14 is water-bath, and semi-permeable membrane layering integrated biological reactor 1 is placed in water-bath, water-bath
Pot uses external hanging type water-bath.It may also set up a holder that can be taken off 14.1 in water-bath, semi-permeable membrane layering one when heating
Formula bioreactor 1 is put into holder 14.1.
Integrated system further includes multiple pressure-detecting devices 29, be respectively arranged on artery pot 13, on venous chambers 15, separation pump
In connecting tube 20, between blood input port 11 and blood pump 12.
Interlayer 32 is additionally provided with the sealed support for obstructing blood plasma/priming fluid between air inlet 30 and permeable fiber silk 22
Plate 33；Sealed support plate 33 is arranged with 30 spacing of air inlet；Multiple apertures are offered on sealed support plate 33；Permeable fiber silk 22
One end is fastened in aperture, and is connected with air inlet 30 by the space between sealed support plate 33 and air inlet 30.
Integrated system further includes 37 DEG C of heat-preserving heating jacket (not shown) being set to outside cavity 2 and shaking table (not shown).Pass through
The effect of heating mantle so that semi-permeable membrane layering 1 temperature control of integrated biological reactor of the invention is 37 DEG C, and the work for passing through shaking table
With making its sustainable shake, avoid cell accumulation, therapeutic effect is made to perform to most preferably.
The aperture for separating semi-permeable membrane 3 is 0.3~5 micron, and the aperture of undermost filtering semi-permeable membrane 8 is 5 microns.
The liver cell perfusion of the present invention is microcarrier perfusion, i.e., leads to the cell being attached on microcarrier together with microcarrier
It crosses each liver cell perfusing hole 9 to be fed into, perfusion volume is about the 2/3 of 10 volume of filtering layer space.
Treatment starts, and after the blood lead body of liver failure patient is outer, blood enters plasma separator 1.1 from blood entry port 4
In, under the action of hollow fibre filament 6, blood is detached, and haemocyte and part blood plasma are flowed out from haemocyte outlet 5, remainder
Point blood plasma pumps connecting tube 20 by separation under the action of separation pump 24 and enters in bioreactor 1.2；Blood plasma, which is first in, to be set
Have in the interlayer 32 of permeable fiber silk 22, air inlet 30 is filled with oxygen into interlayer 32, and blood plasma penetrates undermost filtering later
Semi-permeable membrane 8 enters filtering layer space 10, and is fully reacted with the cell in the filtering layer space 10, carries out, successively passes through successively
Semi-permeable membrane 8 is filtered, until blood plasma penetrates the filtering semi-permeable membrane 8 of top layer, is discharged finally by plasma outlet port 7, and and haemocyte
Human body is inputted after the haemocyte of 5 discharge of outlet and the mixing of part blood plasma, forms a treatment circulation circuit.
During treatment carries out, the upstream reason biochemical indicator detecting head 25.3 at its both ends, downstream are utilized by biomonioring device 25
Manage biochemical indicator detecting head 25.4 respectively the blood plasma bilirubin of monitoring disengaging semi-permeable membrane layering integrated biological reactor 1, ammonia,
TT＆C system 25.1 is supervised in the variation of the biochemical indicators such as creatinine, urea nitrogen, liver enzyme, albumin, hemoglobin, red blood cell, leucocyte
Immediately it obtains and handles institute's monitoring data, and whole system is fed back by signal feedback system 25.2 to implement to control.
After treatment end, used consumptive material is handled；Transducer potector etc. is removed from artificial liver machine equipment and
It is discarded according to the discarded step of hospital facility.
Claims (10)
1. a kind of semi-permeable membrane layer-stepping bioartificial liver on-line monitoring and heated at constant temperature integrated system, it is characterised in that：Including suitable
The connected blood input port (11) of sequence, blood pump (12), artery pot (13), semi-permeable membrane layering integrated biological reactor (1), vein
Pot (15) and blood recovery mouth (16)；
The semi-permeable membrane layering integrated biological reactor (1) includes cavity (2), and the blood plasma in cavity (2) side is arranged and detaches
Device (1.1) and setting cavity (2) other side bioreactor (1.2)；Plasma separator (1.1) and bioreactor
(1.2) it is spaced apart by separating semi-permeable membrane (3)；
Blood entry port (4) and haemocyte outlet (5), blood are offered on the cavity (2) of plasma separator (1.1) side
It starches and is filled with more hollow fibre filaments (6) inside separator (1.1)；Described hollow fibre filament (6) one end connects with blood entry port (4)
Logical, the other end is connected to haemocyte outlet (5)；
Plasma outlet port (7), bioreactor are offered at the top of the cavity (2) of the other side where bioreactor (1.2)
(1.2) being horizontally disposed in has a multiple filtration semi-permeable membrane (8), and the filtering semi-permeable membrane (8) is used to obstruct free cell and passes through and phase
Two adjacent filtering semi-permeable membranes (8) form an independent filtering layer space (10) together with the side wall of bioreactor (1.2), often
The corresponding cavity (2) of a independent filtering layer space (10) is equipped with liver cell perfusing hole (9)；The filtering semi-permeable membrane (8) of top layer
It is detached with holding at the top of bioreactor (1.2)；Undermost filtering semi-permeable membrane (8) is formed with bioreactor (1.2) bottom
Interlayer (32) is equipped with filled with permeable fiber silk (22) and the corresponding cavity (2) of the interlayer (32) in the interlayer (32)
Air inlet (30), the air inlet (30) are only connected to permeable fiber silk (22)；
The plasma separator (1.1) and bioreactor (1.2) pump connecting tube (20) by being equipped with the separation of separation pump (24)
The two is connected to；The arrival end of the separation pump connecting tube (20) is located at the cavity of the plasma separator (1.1) side
(2) side wall lower ends, outlet end are located at the bottom of the cavity (2) of the bioreactor (1.2) side；
The blood entry port (4) is connected with the outlet of artery pot (13), and the plasma outlet port (7) exports (5) together with haemocyte
It is connected with the entrance of the venous chambers (15)；
The integrated system is additionally provided with pipeline heating device (14).
2. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：The filtering semi-permeable membrane (8) and separation semi-permeable membrane (3) are flat membrane element, the periphery of the flat membrane element
It is bonded fixation with cavity (2)；The aperture of the filtering semi-permeable membrane (8) pumps connecting tube (20) outlet end according to far from the separation
Successively decrease one by one in direction.
3. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 2 and heated at constant temperature integrated system,
It is characterized in that：The barrier semi-permeable membrane (17) for preventing cell permeable is equipped in the plasma outlet port (7).
4. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 3 and heated at constant temperature integrated system,
It is characterized in that：It is additionally provided with alternate outlets (18) and pressure sensor (19) on the corresponding cavity (2) of the filtering layer space (10).
5. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：Hyperoxia water inlet (21) is offered at the blood entry port (4)；It is further opened on the plasma separator (1.1)
The spare adding mouth of plasma separator (23)；The corresponding cavity (2) of the interlayer (32) is equipped with gas outlet/reserved opening (31).
6. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：The integrated system includes the biomonioring device (25) for continuously monitoring biochemical indicator on-line, the biochemistry
Monitoring device (25) is electric including prison TT＆C system (25.1), signal feedback system (25.2) and with the prison TT＆C system (25.1)
The upstream reason biochemical indicator detecting head (25.3) and downstream reason biochemical indicator detecting head (25.4) of signal connection；The upstream reason life
Change index detecting head (25.3) to be set at the blood input port (11), the downstream reason biochemical indicator detecting head (25.4) is set to
At the blood recovery mouth (16).
7. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：It is respectively equipped with use on the artery pot (13), on venous chambers (15), between blood pump (12) and blood input port (11)
In addition drug or the branch pipe (26) of liquid；The heparin for injecting heparin is equipped between the blood pump (12) and artery pot (13)
Branch pipe (27).
8. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：It is additionally provided between the venous chambers (15) and the blood recovery mouth (16) for monitoring in pipeline whether have air
Air monitoring device (28).
9. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：The pipeline heating device (14) is water-bath, and semi-permeable membrane layering integrated biological reactor (1) is placed in water-bath
In pot, the water-bath uses external hanging type water-bath.
10. semi-permeable membrane layer-stepping bioartificial liver on-line monitoring according to claim 1 and heated at constant temperature integrated system,
It is characterized in that：The integrated system further includes multiple pressure-detecting devices (29), is respectively arranged on artery pot (13), venous chambers
(15) on, in separation pump connecting tube (20), between blood input port (11) and blood pump (12).
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| CN201610608802.XA CN106267402B (en) | 2016-07-29 | 2016-07-29 | Semi-permeable membrane layer-stepping bioartificial liver monitors on-line and heated at constant temperature integrated system |
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| CN106267402B true CN106267402B (en) | 2018-07-17 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1127995A (en) * | 1992-09-11 | 1996-07-31 | 艾格塞诺吉耐克斯股份有限公司 | Artificial liver apparatus and method |
| CN1254599A (en) * | 1998-11-20 | 2000-05-31 | 四川联合大学 | Plasma separator of hollow fibre membrane and its blood taking and separating method |
| CN1330959A (en) * | 2000-06-29 | 2002-01-16 | 重庆西南医院 | Method and equipment for externally mixed biologic artificial liver |
| CN104379190A (en) * | 2012-11-26 | 2015-02-25 | 甘布罗伦迪亚股份公司 | Liver support system |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7160719B2 (en) * | 2002-06-07 | 2007-01-09 | Mayo Foundation For Medical Education And Research | Bioartificial liver system |
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2016
- 2016-07-29 CN CN201610608802.XA patent/CN106267402B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1127995A (en) * | 1992-09-11 | 1996-07-31 | 艾格塞诺吉耐克斯股份有限公司 | Artificial liver apparatus and method |
| CN1254599A (en) * | 1998-11-20 | 2000-05-31 | 四川联合大学 | Plasma separator of hollow fibre membrane and its blood taking and separating method |
| CN1330959A (en) * | 2000-06-29 | 2002-01-16 | 重庆西南医院 | Method and equipment for externally mixed biologic artificial liver |
| CN104379190A (en) * | 2012-11-26 | 2015-02-25 | 甘布罗伦迪亚股份公司 | Liver support system |
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