CN106267402A - Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring and heated at constant temperature integrated system - Google Patents
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring and heated at constant temperature integrated system Download PDFInfo
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- CN106267402A CN106267402A CN201610608802.XA CN201610608802A CN106267402A CN 106267402 A CN106267402 A CN 106267402A CN 201610608802 A CN201610608802 A CN 201610608802A CN 106267402 A CN106267402 A CN 106267402A
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- 239000012528 membrane Substances 0.000 title claims abstract description 95
- 210000004185 liver Anatomy 0.000 title claims abstract description 36
- 238000012544 monitoring process Methods 0.000 title claims abstract description 31
- 210000004369 blood Anatomy 0.000 claims abstract description 64
- 239000008280 blood Substances 0.000 claims abstract description 64
- 210000002381 plasma Anatomy 0.000 claims abstract description 64
- 238000001914 filtration Methods 0.000 claims abstract description 50
- 210000004027 cell Anatomy 0.000 claims abstract description 31
- 238000011084 recovery Methods 0.000 claims abstract description 10
- 239000000835 fiber Substances 0.000 claims description 20
- 239000011229 interlayer Substances 0.000 claims description 17
- 239000010410 layer Substances 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 15
- 238000000926 separation method Methods 0.000 claims description 14
- 210000003677 hemocyte Anatomy 0.000 claims description 13
- 229940000351 hemocyte Drugs 0.000 claims description 13
- 210000003494 hepatocyte Anatomy 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 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
- 229920000669 heparin Polymers 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000012806 monitoring device Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 238000010030 laminating Methods 0.000 claims description 3
- 210000003462 vein Anatomy 0.000 claims description 3
- 230000005611 electricity Effects 0.000 claims 1
- 239000002002 slurry Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 239000000463 material Substances 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000010412 perfusion Effects 0.000 description 5
- 206010019663 Hepatic failure Diseases 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 208000007903 liver failure Diseases 0.000 description 4
- 231100000835 liver failure Toxicity 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 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
- 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
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 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
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 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
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- Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- External Artificial Organs (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses semipermeable membrane layer-stepping bioartificial liver's on-line monitoring and heated at constant temperature integrated system, blood input port, blood pump, tremulous pulse kettle, semipermeable membrane layering integrated biological reactor, venous chambers and the blood recovery mouth being connected including order；Semipermeable membrane layering integrated biological reactor includes cavity, is arranged on the plasma separator of cavity side and is arranged on the bioreactor of cavity opposite side；Plasma separator and bioreactor are spaced apart by separating semipermeable membrane；Multiple filtration semipermeable membrane it has been horizontally disposed with in bioreactor.The invention has the beneficial effects as follows: design more simple and practical；Being fully contacted between cell and blood plasma, be conducive to improving the exchange efficiency of two class materials, degraded blood plasma effect is more preferable；Increase cell parking space, increase useful load.
Description
Technical field
The invention belongs to bioartificial liver's technical field, particularly relate to a kind of semipermeable membrane layer-stepping bioartificial liver and supervise online
Survey and heated at constant temperature integrated system.
Background technology
Liver failure patient populations is huge in China, and the effective treatment means seeking new liver failure becomes urgently to be resolved hurrily
Problem.Bioartificial liver system can maintain patients ' lives, waits liver transplantation chance, or the chance that patient self liver recovers, is recent
The focus of research and development.Biological artificial liver support system, mainly by having the cell mass of liver metabolism function, to hepatic failure patients
Blood purifies, it is achieved the function that Vitro hepatic ramus splanchnicus is held, and wins the quality time for liver regeneration or wait liver transplantation, tool
There is important clinical using value.
Bioreactor is the core of bioartificial liver, and its performance is directly connected to support and the treatment effect of artificial liver
Really.The class bioreactor studied at present and be most widely used is hollow fiber type reactor, the structure one of this reactor
As be made up of cylindrical reactor shell and the doughnut filled in housing, doughnut bunchy arranges, in hollow fiber walls
Having the aperture that can be used for exchange, its advantage is to isolate foreign protein, can prevent heterologous protein from entering human body and cause allergy
Reaction, prevents the human body interior preexisting antibody for the heterogenous cell antigen lethal effect to cell simultaneously.But this kind of reactor is also
There are some problems, such as limited volume, loading cells amount is little, and culture fluid or blood are limited with hepatocyte exchange area, it addition, carefully
Easily block fiber fenestra during intracellular growth, affect the mass exchange inside and outside film further, be unfavorable for hepatocellular function and vigor
Permanently effective maintenance and effectively treating.And current existing bioartificial liver's reactor heats just with heat booster, and
Bioartificial liver's reactor can not be carried out heated at constant temperature, add thermally labile, affect the efficiency of bioartificial liver's reactor.
Preferably bioartificial liver system should possess following characteristics: system is simple, easy and simple to handle；Can provide suitable for cell
Metabolism environment, ensures cytoactive；The cell distribution of perfusion is uniform, and loading cells amount is big, cell can with blood plasma be fully contacted into
Row mass exchange.
Summary of the invention
The purpose of the present invention overcomes existing bioartificial liver system structure complicated, complex operation, the biology that system is corresponding
Reactor volume is limited, loading cells amount is little, blood plasma and the problem such as hepatocyte exchange area is limited, cell distribution is uneven, carries
For a kind of semipermeable membrane layer-stepping bioartificial liver's on-line monitoring and heated at constant temperature integrated system, it is simple that it has system, operation letter
Just, the features such as loading cells amount, heated at constant temperature, the exchange efficiency of raising material and uniformity coefficient are increased.
For achieving the above object, the semipermeable membrane layer-stepping bioartificial liver's on-line monitoring designed by the present invention and heated at constant temperature
Integrated system, including the blood input port being sequentially connected, blood pump, tremulous pulse kettle, semipermeable membrane layering integrated biological reactor, vein
Kettle and blood recovery mouth；
Described semipermeable membrane layering integrated biological reactor includes cavity, is arranged on the plasma separator of cavity side and sets
Put the bioreactor at cavity opposite side；Plasma separator and bioreactor are spaced apart by separating semipermeable membrane；
It is positioned on the cavity of plasma separator side and offers blood entry port and hemocyte outlet, in plasma separator
Portion is filled with many hollow fibre filaments；Described hollow fibre filament one end connects with blood entry port, and the other end is with hemocyte outlet even
Logical；
The top of the cavity being positioned at bioreactor place opposite side offers plasma outlet port, and in bioreactor, level sets
Be equipped with multiple filtration semipermeable membrane, described filtration semipermeable membrane for intercept free cell through and adjacent two filtration semipermeable membranes with
The sidewall of bioreactor forms an independent filtering layer space together, and cavity corresponding to each independent filtering layer space is provided with
Hepatocyte perfusing hole；The filtration semipermeable membrane of the superiors keeps separating with bioreactor top；Undermost filtration semipermeable membrane with
Form interlayer bottom bioreactor, be filled with permeable fiber silk in described interlayer and cavity corresponding to described interlayer be provided with into
QI KOU, described air inlet only connects with permeable fiber silk；
Both are connected by being provided with the separation pump connecting tube separating pump by described plasma separator with bioreactor；Described
The arrival end of separation pump connecting tube is positioned at the side wall lower ends of the cavity of described plasma separator side, and the port of export is positioned at described
The bottom of the cavity of bioreactor side；
Described blood entry port is connected with the outlet of tremulous pulse kettle, the outlet of described plasma outlet port and hemocyte in the lump with described vein
The entrance of kettle is connected；
Described integrated system is additionally provided with pipeline heating device.
Further, described filtration semipermeable membrane and separation semipermeable membrane are flat membrane element, the week of described flat membrane element
Limit is fixing with cavity laminating；The aperture of described filtration semipermeable membrane is according to the direction away from the described separation pump connecting tube port of export one by one
Successively decrease.
Above-mentioned further scheme provides the benefit that: successively decrease one by one by being used by the surface pores diameter filtering semipermeable membrane
Mode arrange, be possible not only to prevent filter semipermeable membrane and block, also can guarantee that plasma flow rate is uniform and stable.
Yet further, the obstruct semipermeable membrane of prevention cell permeable it is provided with in described plasma outlet port.
Above-mentioned further scheme provides the benefit that: by intercepting the effect of semipermeable membrane, be avoided that cell or cellular products
Enter blood, intercept macromolecular substances and pass through, prevent allergy.
Further, the cavity that described filtering layer space is corresponding is additionally provided with alternate outlets and pressure transducer.
Above-mentioned further scheme provides the benefit that: detected whether that filtering semipermeable membrane occurs stifled by pressure transducer
Plug, when a jam does occur, connects two alternate outlets by connecting tube, prevents filtering semipermeable membrane and occurs to cause in circulation during blocking
Disconnected, make blood plasma pass through connecting tube and enter the next filtering layer space not filtering semipermeable membrane blocking, make treatment proceed.
Further, described blood entry port offers high-oxygen water entrance；It is further opened with blood plasma on described plasma separator
The standby adding mouth of separator；The cavity that described interlayer is corresponding is provided with gas outlet/reserved opening.
Yet further, described integrated system includes the biomonioring device for continuous on-line monitoring biochemical indicator, institute
State biomonioring device to include monitoring Ore-controlling Role, signal feedback system and the upstream reason being connected with the described monitoring Ore-controlling Role signal of telecommunication
Biochemical indicator detecting head and downstream reason biochemical indicator detecting head；Described upstream reason biochemical indicator detecting head is located at the input of described blood
At Kou, described downstream reason biochemical indicator detecting head is located at described blood recovery mouth.
Alternatively, on described tremulous pulse kettle, interpolation medicine on venous chambers, between blood pump and blood input port, it is respectively provided with
Or the arm of liquid；The heparin arm for injecting heparin it is provided with between described blood pump and tremulous pulse kettle.
Preferably, it is additionally provided with for monitoring in pipeline whether have air between described venous chambers and described blood recovery mouth
Air monitoring device.
Further, described pipeline heating device is water-bath, and semipermeable membrane layering integrated biological reactor is as water
In bath, it uses external hanging type to be connected with system.
Preferably, described integrated system also includes multiple pressure-detecting device, be respectively arranged on tremulous pulse kettle, on venous chambers,
Separate in pump connecting tube, between blood input port and blood pump.
The invention has the beneficial effects as follows:
1, by improving the structure of bioartificial liver's reactor in existing bioartificial liver system, plasma separator is anti-with biology
Answer device splicing or directly plasma separator be placed in bioreactor, designing more simple and practical；
2, it is passed through high-oxygen water and ensures cell oxygen supply with oxygenate blood plasma simultaneously, further provided for by the effect of permeable fiber silk
Enough oxygen, can provide suitable metabolism environment for cell, ensure cytoactive, make cell culture effect more preferably, is conducive to thin
The maintenance of born of the same parents' function, improves therapeutic effect；
3, the blood plasma separated enters bioreactor by separating pump connecting tube, after interlayer, more successively sets through spacing
The filtration semipermeable membrane put, carries out mass exchange with the cell in filtering layer space, and blood plasma so can be made to remain stable uniform
Flow velocity, is fully contacted between cell and blood plasma, is conducive to improving the exchange efficiency of two class materials, and degraded blood plasma effect is more preferable；
4, increase cell parking space, increase useful load；
5, reduce cell by the effect of filtration semipermeable membrane, obstruct semipermeable membrane and enter the risk of human body with blood plasma；
6, filtering semipermeable membrane uses multilamellar to arrange, and improves the use effect of cell for bioreactor in parallel
Rate, makes therapeutic effect perform to most preferably；
7, by the effect of pipeline heating device so that the cell in bioreactor can carry out constant temperature water bath heating,
Homogeneous heating, thermal-stable is good；And pipeline heating device uses external hanging type, save space so that system structure is simple；
8, by the effect of biomonioring device so that the pressure of biochemical indicator, blood plasma or blood can be carried out by system
On-line monitoring.
Accompanying drawing explanation
Fig. 1 is the structural representation of semipermeable membrane layer-stepping bioartificial liver's on-line monitoring of the present invention and heated at constant temperature integrated system
Figure.
Fig. 2 is the structural representation of the semipermeable membrane layering integrated biological reactor in Fig. 1.
Fig. 3 is the perspective view of the pipeline heating device in Fig. 1.
Fig. 4 is the sectional structure schematic diagram of Fig. 3.
In figure, semipermeable membrane is layered integrated biological reactor 1, plasma separator 1.1, bioreactor 1.2, cavity 2, divides
Every semipermeable membrane 3, blood entry port 4, hemocyte outlet 5, hollow fibre filament 6, plasma outlet port 7, filter semipermeable membrane 8, hepatocyte perfusion
Mouthfuls 9, filtering layer space 10, blood input port 11, blood pump 12, tremulous pulse kettle 13, pipeline heating device 14, support 14.1, venous chambers 15,
Blood recovery mouth 16, obstruct semipermeable membrane 17, alternate outlets 18, pressure transducer 19, separation pump connecting tube 20, high-oxygen water entrance
21, permeable fiber silk 22, the standby adding mouth of plasma separator 23, separation pump 24, biomonioring device 25, monitoring Ore-controlling Role
25.1, signal feedback system 25.2, upstream reason biochemical indicator detecting head 25.3, downstream reason biochemical indicator detecting head 25.4, arm
26, heparin arm 27, air monitoring device 28, pressure-detecting device 29, air inlet 30, gas outlet/reserved opening 31, interlayer 32,
Sealed support plate 33.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, the present invention is described in further detail.
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring as shown in figures 1-4 and heated at constant temperature integrated system, including suitable
Blood input port 11, blood pump 12, tremulous pulse kettle 13, semipermeable membrane layering integrated biological reactor 1, venous chambers 15 and the blood that sequence is connected
Liquid feeds back mouth 16；
Semipermeable membrane layering integrated biological reactor 1 include cavity 2, be arranged on cavity 2 side plasma separator 1.1 and
It is arranged on the bioreactor 1.2 of cavity 2 opposite side；Plasma separator 1.1 and bioreactor 1.2 are by separating semipermeable membrane 3
Spaced apart；
Being positioned on the cavity 2 of plasma separator 1.1 side and offer blood entry port 4 and hemocyte outlet 5, blood plasma divides
It is filled with many hollow fibre filaments 6 from device 1.1 inside；Hollow fibre filament 6 one end connects with blood entry port 4, and the other end is thin with blood
Born of the same parents export 5 connections；
The top of the cavity 2 being positioned at bioreactor 1.2 place opposite side offers plasma outlet port 7, bioreactor 1.2
Inside it is horizontally disposed with multiple filtration semipermeable membrane 8, has filtered semipermeable membrane 8 and pass and adjacent two filtrations half for intercepting free cell
Permeable membrane 8 forms an independent filtering layer space 10 together with the sidewall of bioreactor 1.2, and each independent filtering layer space 10 is right
The cavity 2 answered is provided with hepatocyte perfusing hole 9；The filtration semipermeable membrane 8 of the superiors keeps separating with bioreactor 1.2 top；
Form interlayer 32 bottom undermost filtration semipermeable membrane 8 and bioreactor 1.2, be filled with in interlayer 32 permeable fiber silk 22 and
The cavity 2 of interlayer 32 correspondence is provided with air inlet 30, and air inlet 30 only connects with permeable fiber silk 22；
Both are connected by plasma separator 1.1 and bioreactor 1.2 by being provided with the separation pump connecting tube 20 separating pump 24
Logical；The arrival end of separation pump connecting tube 20 is positioned at the side wall lower ends of the cavity 2 of plasma separator 1.1 side, port of export position
Bottom in the cavity 2 of bioreactor 1.2 side；
Blood entry port 4 is connected with the outlet of tremulous pulse kettle 13, plasma outlet port 7 and hemocyte outlet 5 in the lump with venous chambers 15
Entrance is connected；
Integrated system is additionally provided with pipeline heating device 14.
Filtering semipermeable membrane 8 and separation semipermeable membrane 3 is flat membrane element, the periphery of flat membrane element is solid with cavity 2 laminating
Fixed；Successively decrease one by one according to away from the direction separating pump connecting tube 20 port of export in the aperture filtering semipermeable membrane 8.Semi-transparent by filtering
The surface pores diameter of film 8 uses the mode successively decreased one by one to arrange, and is possible not only to prevent filtering semipermeable membrane 8 and blocks, also can
Ensure that plasma flow rate is uniform and stable.
The obstruct semipermeable membrane 17 stoping cell permeable it is provided with in plasma outlet port 7.By intercepting the effect of semipermeable membrane 17, can keep away
Exempt from cell or cellular products enters blood, intercept macromolecular substances and pass through, prevent allergy.
Alternate outlets 18 and pressure transducer 19 it is additionally provided with on the cavity 2 of filtering layer space 10 correspondence.Pass through pressure transducer
19 detected whether filter semipermeable membrane 8 block, when a jam does occur, by connecting tube (not shown) connection two standby go out
Mouthful, prevent filtering semipermeable membrane 8 and occur to cause cycle interruption during blocking, make blood plasma pass through the connecting tube entrance next one and do not filter half
The filtering layer space 10 of permeable membrane blocking 8, makes treatment proceed.
High-oxygen water entrance 21 is offered at blood entry port 4；It is further opened with on plasma separator 1.1 that plasma separator is standby to be added
Sample mouth 23；The cavity 2 of interlayer 32 correspondence is provided with gas outlet/reserved opening 31.
Integrated system includes the biomonioring device 25 for continuous on-line monitoring biochemical indicator, and biomonioring device 25 wraps
Include monitoring Ore-controlling Role 25.1, signal feedback system 25.2 and the upstream reason biochemical indicator being connected with monitoring Ore-controlling Role 25.1 signal of telecommunication
Detecting head 25.3 and downstream reason biochemical indicator detecting head 25.4；Upstream reason biochemical indicator detecting head 25.3 is located at blood input port 11
Place, downstream reason biochemical indicator detecting head 25.4 is located at blood recovery mouth 16.
Be respectively provided with on tremulous pulse kettle 13, on venous chambers 15, between blood pump 12 and blood input port 11 interpolation medicine or
The arm 26 of liquid；The heparin arm 27 for injecting heparin it is provided with between blood pump 12 and tremulous pulse kettle 13.
It is additionally provided with between venous chambers 15 and blood recovery mouth 16 and fills for monitoring the air monitering whether having air in pipeline
Put 28.
Pipeline heating device 14 is water-bath, and semipermeable membrane layering integrated biological reactor 1 is as in water-bath, and it is adopted
It is connected with system with external hanging type.A support that can be taken off 14.1 is may also set up, semipermeable membrane layering one during heating in water-bath
Formula bioreactor 1 puts into support 14.1.
Integrated system also includes multiple pressure-detecting device 29, be respectively arranged on tremulous pulse kettle 13, on venous chambers 15, separate pump
In connecting tube 20, between blood input port 11 and blood pump 12.
Interlayer 32 is additionally provided with the sealed support for intercepting blood plasma/priming fluid between air inlet 30 and permeable fiber silk 22
Plate 33；Sealed support plate 33 is arranged with air inlet 30 spacing；Multiple aperture is 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 with air inlet 30.
Integrated system also includes 37 DEG C of heat-preserving heating jacket (not shown) and the shaking table (not shown) being located at outside cavity 2.Pass through
The effect of heating mantle so that semipermeable membrane layering integrated biological reactor 1 temperature control of the present invention is 37 DEG C, and by the work of shaking table
With so that it is sustainable shake, it is to avoid cell accumulation, make therapeutic effect perform to most preferably.
The aperture separating semipermeable membrane 3 is 0.3～5 micron, and the aperture of undermost filtration semipermeable membrane 8 is 5 microns.
The hepatocyte perfusion of the present invention is microcarrier perfusion, and the cell will being attached on microcarrier leads to together with microcarrier
Crossing each hepatocyte perfusing hole 9 to be fed into, perfusion volume is about the 2/3 of filtering layer space 10 volume.
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 effect of hollow fibre filament 6, blood is separated, and hemocyte and part blood plasma are from hemocyte outlet 5 outflow, remainder
Blood plasma is divided to be entered in bioreactor 1.2 by separation pump connecting tube 20 under the effect separating pump 24；Blood plasma is first in setting
In having the interlayer 32 of permeable fiber silk 22, air inlet 30 is filled with oxygen in interlayer 32, and blood plasma passes through undermost filtration afterwards
Semipermeable membrane 8 enters filtering layer space 10, and fully reacts with the cell in this filtering layer space 10, carries out successively, successively passes
Filter semipermeable membrane 8, until blood plasma is through the filtration semipermeable membrane 8 of the superiors, discharge finally by plasma outlet port 7, and and hemocyte
Input human body after the hemocyte of outlet 5 discharge and the mixing of part blood plasma, form a treatment closed circuit.
During treatment is carried out, biomonioring device 25 utilize upstream reason biochemical indicator detecting head 25.3, the downstream at its two ends
Reason biochemical indicator detecting head 25.4 respectively monitor turnover semipermeable membrane be layered the blood plasma bilirubin of integrated biological reactor 1, ammonia,
The change of the biochemical indicators such as creatinine, blood urea nitrogen, liver enzyme, albumin, hemoglobin, erythrocyte, leukocyte, monitors Ore-controlling Role 25.1
Instant acquisition and process institute Monitoring Data, and feed back to implement control to whole system by signal feedback system 25.2.
After treatment terminates, used consumptive material is processed；Transducer potector etc. is taken off from artificial liver machine equipment and
Discarded according to the discarded step of hospital facility.
Claims (10)
1. semipermeable membrane layer-stepping bioartificial liver's on-line monitoring and heated at constant temperature integrated system, it is characterised in that: include suitable
Sequence be connected blood input port (11), blood pump (12), tremulous pulse kettle (13), semipermeable membrane layering integrated biological reactor (1), vein
Kettle (15) and blood recovery mouth (16)；
Described semipermeable membrane layering integrated biological reactor (1) includes cavity (2), and the blood plasma being arranged on cavity (2) side separates
Device (1.1) and be arranged on the bioreactor (1.2) of cavity (2) opposite side；Plasma separator (1.1) and bioreactor
(1.2) spaced apart by separating semipermeable membrane (3)；
It is positioned on the cavity (2) of plasma separator (1.1) side and offers blood entry port (4) and hemocyte outlet (5), blood
Slurry separator (1.1) is internal is filled with many hollow fibre filaments (6)；Described hollow fibre filament (6) one end is with blood entry port (4) even
Logical, the other end connects with hemocyte outlet (5)；
The top of the cavity (2) being positioned at bioreactor (1.2) place opposite side offers plasma outlet port (7), bioreactor
(1.2) being horizontally disposed with multiple filtration semipermeable membrane (8) in, described filtration semipermeable membrane (8) is used for intercepting free cell and passes and phase
Two adjacent filtrations semipermeable membrane (8) form an independent filtering layer space (10), often together with the sidewall of bioreactor (1.2)
The cavity (2) of individual independent filtering layer space (10) correspondence is provided with hepatocyte perfusing hole (9)；The filtration semipermeable membrane (8) of the superiors
Keep separating with bioreactor (1.2) top；Undermost filtration semipermeable membrane (8) is formed with bioreactor (1.2) bottom
Interlayer (32), the cavity (2) being filled with permeable fiber silk (22) and described interlayer (32) correspondence in described interlayer (32) is provided with
Air inlet (30), described air inlet (30) only connects with permeable fiber silk (22)；
Described plasma separator (1.1) and bioreactor (1.2) are by being provided with separation pump connecting tube (20) separating pump (24)
Both are connected；The arrival end of described separation pump connecting tube (20) is positioned at the cavity of described plasma separator (1.1) side
(2) side wall lower ends, the port of export is positioned at the bottom of the cavity (2) of described bioreactor (1.2) side；
Described blood entry port (4) is connected with the outlet of tremulous pulse kettle (13), and described plasma outlet port (7) is with hemocyte outlet (5) in the lump
It is connected with the entrance of described venous chambers (15)；
Described integrated system is additionally provided with pipeline heating device (14).
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described filtration semipermeable membrane (8) and separation semipermeable membrane (3) are flat membrane element, the periphery of described flat membrane element
Fixing with cavity (2) laminating；The aperture of described filtration semipermeable membrane (8) is according to away from described separation pump connecting tube (20) port of export
Successively decrease one by one in direction.
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 2 and heated at constant temperature integrated system, its
It is characterised by: in described plasma outlet port (7), be provided with the obstruct semipermeable membrane (17) stoping cell permeable.
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 3 and heated at constant temperature integrated system, its
It is characterised by: on the cavity (2) that described filtering layer space (10) is corresponding, be additionally provided with alternate outlets (18) and pressure transducer (19).
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described blood entry port (4) place offers high-oxygen water entrance (21)；Described plasma separator is further opened with on (1.1)
The standby adding mouth of plasma separator (23)；The cavity (2) that described interlayer (32) is corresponding is provided with gas outlet/reserved opening (31).
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described integrated system includes the biomonioring device (25) for continuous on-line monitoring biochemical indicator, described biochemistry
Monitoring device (25) include monitor Ore-controlling Role (25.1), signal feedback system (25.2) and with described monitoring Ore-controlling Role (25.1) electricity
Biochemical indicator detecting head (25.4) is managed in upstream reason biochemical indicator detecting head (25.3) and downstream that signal connects；Described upstream reason is raw
Changing index detecting head (25.3) and be located at described blood input port (11) place, described downstream reason biochemical indicator detecting head (25.4) is located at
Described blood recovery mouth (16) place.
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described tremulous pulse kettle (13) is upper, venous chambers (15) is upper, be respectively equipped with use between blood pump (12) and blood input port (11)
In adding medicine or the arm (26) of liquid；The heparin for injecting heparin it is provided with between described blood pump (12) and tremulous pulse kettle (13)
Arm (27).
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: be additionally provided with for monitoring in pipeline whether have air between described venous chambers (15) and described blood recovery mouth (16)
Air monitoring device (28).
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described pipeline heating device (14) is water-bath, and semipermeable membrane layering integrated biological reactor (1) is as water-bath
In pot, it uses external hanging type to be connected with system.
Semipermeable membrane layer-stepping bioartificial liver's on-line monitoring the most according to claim 1 and heated at constant temperature integrated system, its
It is characterised by: described integrated system also includes multiple pressure-detecting device (29), is respectively arranged on that tremulous pulse kettle (13) is upper, venous chambers
(15) above, pump connecting tube (20) is separated upper, between blood input port (11) and blood pump (12).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112399891A (en) * | 2018-07-26 | 2021-02-23 | 株式会社岛津制作所 | Flow pattern field flow separating device |
Citations (5)
| 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 |
| US20030228685A1 (en) * | 2002-06-07 | 2003-12-11 | Nyberg Scott L. | Bioartificial liver system |
| CN104379190A (en) * | 2012-11-26 | 2015-02-25 | 甘布罗伦迪亚股份公司 | Liver support system |
-
2016
- 2016-07-29 CN CN201610608802.XA patent/CN106267402B/en active Active
Patent Citations (5)
| 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 |
| US20030228685A1 (en) * | 2002-06-07 | 2003-12-11 | Nyberg Scott L. | Bioartificial liver system |
| CN104379190A (en) * | 2012-11-26 | 2015-02-25 | 甘布罗伦迪亚股份公司 | Liver support system |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112399891A (en) * | 2018-07-26 | 2021-02-23 | 株式会社岛津制作所 | Flow pattern field flow separating device |
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| CN106267402B (en) | 2018-07-17 |
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