CN206167482U - Trinity formula artificial liver bioreactor - Google Patents

Trinity formula artificial liver bioreactor Download PDF

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Publication number
CN206167482U
CN206167482U CN201620809802.1U CN201620809802U CN206167482U CN 206167482 U CN206167482 U CN 206167482U CN 201620809802 U CN201620809802 U CN 201620809802U CN 206167482 U CN206167482 U CN 206167482U
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CN
China
Prior art keywords
oxygenator
reactor
plasma separator
polyurethane resin
artificial liver
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Expired - Fee Related
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CN201620809802.1U
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Chinese (zh)
Inventor
周平
刘路
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Zhejiang Tonggan Medical Technology Co ltd
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Wuhan Tong Stem Medical Polytron Technologies Inc
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Priority to CN201620809802.1U priority Critical patent/CN206167482U/en
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Abstract

The utility model discloses a trinity formula artificial liver bioreactor, including blood plasma separator, oxygenator and the reactor of hugging closely the setting side by side, blood plasma separator with the oxygenator lateral wall that shares, and through ware room connecting pipe from the outside with both inner chambers intercommunications, be equipped with separation pump on the connecting pipe of ware room, the reactor with oxygenator another lateral wall that shares, and through the intercommunicating pore offered on it with both inner chambers intercommunications. The beneficial effects of the utility model are that: after blood got into blood plasma separator, direct oxygenator and the reactor of getting into in proper order of plasma reduced the unnecessary pipeline, can provide suitable metabolism environment, guarantee cell activity for the cell, improve effective cell packing volume, guarantee that cell transverse distribution is even.

Description

Three-in-one type bioreactor of artificial liver
Technical field
The utility model belongs to bioartificial liver's technical field, more particularly to a kind of three-in-one type artificial liver biological respinse Device.
Background technology
Biological artificial liver support system, it is main using the cell mass with liver metabolism function, to hepatic failure patients blood Purified, realized the function that Vitro hepatic ramus splanchnicus is held, be that the quality time is won in liver regeneration or wait liver transplant, with weight Want clinical value.In biological artificial liver support system, bioreactor provides suitable as core apparatus for cell mass Physiological environment, makes intracellular enzyme activity play greatest benefit, is to realize that efficient liver function expression provides safeguard.
At present, having been used for the biological artificial liver support system of clinical testing or treatment mainly includes plasma separator, oxygen coupling Clutch and the part of bioreactor three.After patient blood is derived in vitro, first menses slurry separator separates blood plasma and haemocyte; The blood plasma isolated enters bioreactor Jing after the enough oxygen of oxygen coupler load;Cell mass is with blood plasma in bioreactor Basic nutrition carries out metabolism and exchange;Blood plasma after removal biotoxin separates again blood cells with plasma separator and mixes Close, be fed back in patient's body, realize external artificial liver function.Plasma separator, oxygen coupler and bioreactor three Divide relatively costly, operation is cumbersome, need further optimization.Also, at present conventional bioreactor is hollow fiber type reaction Device, fibre pipe arrangement is tight in the reactor, and volume is less between fibre pipe, and centre is difficult to be loaded into cell, easily causes thin Born of the same parents' skewness, causes system detoxifying properties to reduce.
Preferably bioreactor of artificial liver should possess following characteristics:Suitable metabolism environment can be provided for cell, ensure thin Cytoactive;Sufficient amount cell can be loaded, filling cell distribution is uniform, and cell can be fully contacted with blood plasma and carry out mass exchange; System architecture is succinct, simple operation.
Utility model content
The purpose of this utility model seeks to overcome plasma separator in existing biological artificial liver support system, oxygen coupling Device and the departmental cost of bioreactor three are higher, operate cumbersome, baroque defect, there is provided one kind realize blood plasma separate, Oxygen is coupled and bioreactor is three-in-one and while realizes that pH regulates and controls, cell filling is uniform, mass exchange is sufficiently simple to operate Three-in-one bioreactor of artificial liver.
For achieving the above object, the three-in-one type bioreactor of artificial liver designed by the utility model, including tight side by side Be sticked plasma separator, oxygenator and the reactor put;
The plasma separator shares side wall with the oxygenator, and will both inner chambers from outside by device room connecting tube Connection, device room connecting tube is provided with separation pump;The reactor shares opposite side wall with the oxygenator, and by opening up thereon Intercommunicating pore will both inner spaces;
The upper end of the plasma separator is provided with blood/priming fluid entrance, and lower end is provided with haemocyte outlet;The blood/ With the hollow fiber bundle connection inside plasma separator between priming fluid entrance and haemocyte outlet;
The upper end of the oxygenator is provided with oxygen/carbon dioxide entrance, and the inside of the oxygenator is provided with and oxygen/dioxy Change the permeable fiber membrane tube that carbon entrance is connected;
The side wall of the reactor is provided with the nutrient solution/hepatocyte suspension entrance with its inner space and nutrient solution/liver Cell suspending liquid is exported, and the lower end of the reactor is provided with blood plasma/priming fluid outlet, and the intercommunicating pore and blood plasma/priming fluid go out Mouth is with located at the connection of the hollow fiber film tube of inside reactor.
Further, the inlet end of device room connecting tube is located at the side wall lower ends of the plasma separator, liquid outlet End is positioned at the lower end of the oxygenator;The intercommunicating pore is located at the upper end of oxygenator and reactor.
Yet further, it is additionally provided with for intercepting the close of blood plasma/priming fluid along its cross-sectional direction inside the oxygenator Envelope supporting plate, the sealed support plate is located at the top of intercommunicating pore;Multiple apertures are offered on the sealed support plate, it is described The upper end of gas fiber membrane tube is fastened in aperture, and the space formed by sealed support plate and oxygenator inner cavity top, with oxygen Gas/carbon dioxide entrance is connected.
The beneficial effect of above-mentioned further scheme is:Permeable fiber membrane tube is fixed on by oxygenator by sealed support plate It is interior, both can ensure that oxygen/carbon dioxide entrance was connected with permeable fiber membrane tube, gas is not intercepted, and obstruct blood can be played again The effect of slurry/priming fluid.
Further, two are additionally provided with for intercepting cell and liquid along its cross-sectional direction inside the plasma separator The polyurethane resin supporting plate that body passes through, two polyurethane resin supporting plates are located at respectively plasma separator upper and lower ends and and blood Slurry separator end inner chamber is kept at a distance, and multiple through holes, the hollow fiber bundle are offered on the polyurethane resin supporting plate Two ends be arranged in respectively in the through hole of different polyurethane resin supporting plates, the inlet end of device room connecting tube is located at two Between polyurethane resin supporting plate.Arranging polyurethane resin supporting plate can realize hollow fiber bundle inside plasma separator The purpose of even distribution, rather than blood/priming fluid entrance and haemocyte outlet are all filled in in the end of hollow fiber bundle.
Preferably, the inside reactor is additionally provided with two for intercepting cell and liquid passes through along its cross-sectional direction Polyurethane resin rack plate, two polyurethane resin rack plates be located at respectively reactor upper and lower ends and with reactor end inner chamber Keep at a distance, offer multiple through holes on the polyurethane resin rack plate, the two ends of the hollow fiber film tube are blocked set respectively In the through hole of different polyurethane resin rack plates, the intercommunicating pore is located at the top of polyurethane resin rack plate, the nutrition Liquid/hepatocyte suspension entrance and nutrient solution/hepatocyte suspension outlet are located between two polyurethane resin rack plates.Arrange Polyurethane resin rack plate can realize hollow fiber film tube in the equally distributed purpose of inside reactor.
Alternatively, the plasma separator is additionally provided with and plasma separator inner chamber between two polyurethane resin supporting plates The standby adding mouth of plasma separator of connection and plasma separator outlet;The lower end of the oxygenator is provided with oxygenator sample-adding Mouthful;The inlet end of device room connecting tube connects with the plasma separator outlet;The liquid outlet of device room connecting tube End connects with the oxygenator adding mouth.
Further, the upper end of the oxygenator is additionally provided with the standby adding mouth of oxygenator, the adding mouth and sealed support Space below plate is connected;The lower end of the oxygenator is provided with the adding mouth for infusion medicine-feeding.
Preferably, the permeable fiber membrane tube is tortuous is arranged, and its upper end connects with the oxygen/carbon dioxide entrance, under Hold as blind end.
Alternatively, the blood plasma/priming fluid outlet is provided with polyethersulfone filter film, polyethylene filter membrane or poly ethylene vinyl alcohol Filter membrane, its thickness is 100 μm ± 25 μm, and membrane aperture is 0.5 μm ± 0.1 μm.
Further, it is additionally provided with the Micropump spare interface for communicating therewith on the oxygenator adding mouth.It is standby by Micropump The nutriments such as interface supply glucose.
The beneficial effects of the utility model are:Blood is entered after plasma separator, the blood plasma isolated by hollow fiber bundle Oxygenator and reactor are directly sequentially entered, unnecessary pipeline is reduced, simplifies operation, realize that blood plasma is separated, oxygen is coupled and raw Thing reactor is three-in-one;Permeable fiber membrane tube is provided with by the inside complications in oxygenator and by blood plasma inflow direction and gas Body is filled with direction and is oppositely arranged, and for reactor enough oxygen is provided, while participating in dioxy to permeable fiber membrane tube timely and appropriate discovery Change carbon and realize that pH is adjusted, maintain pH environment more stable in bioreactor, suitable metabolism environment can be provided for cell, ensure thin Cytoactive.
Description of the drawings
Fig. 1 is the structural representation of the utility model three-in-one type bioreactor of artificial liver.
Fig. 2 is the cross section structure diagram of Fig. 1.
In figure, plasma separator 1, oxygenator 2, reactor 3, blood/priming fluid entrance 4, haemocyte outlet 5, hollow fibre Dimension beam 6, oxygen/carbon dioxide entrance 7, permeable fiber membrane tube 8, intercommunicating pore 9, nutrient solution/hepatocyte suspension entrance 10, nutrition Liquid/hepatocyte suspension outlet 11, blood plasma/priming fluid outlet 12, hollow fiber film tube 13, adding mouth 14, polyurethane resin Frame plate 15, polyurethane resin rack plate 16, separation pump 17, polyethersulfone filter film 18, sealed support plate 19, plasma separator are standby The standby adding mouth 22 of adding mouth 20, plasma separator outlet 21, oxygenator, oxygenator adding mouth 23, Micropump spare interface 24, Device room connecting tube 25.
Specific embodiment
The utility model is described in further detail below in conjunction with the drawings and specific embodiments.
Three-in-one type bioreactor of artificial liver as shown in Figure 1 and Figure 2, including the plasma separator for being close to arrange side by side 1st, oxygenator 2 and reactor 3;
Plasma separator 1 shares side wall with oxygenator 2, and is connected both inner chambers from outside by device room connecting tube 25 Logical, device room connecting tube 25 is provided with separation pump 17;Reactor 3 shares opposite side wall, and the company by opening up thereon with oxygenator 2 Through hole 9 will both inner spaces;
The upper end of plasma separator 1 is provided with blood/priming fluid entrance 4, and lower end is provided with haemocyte outlet 5, blood/priming fluid Connected with the hollow fiber bundle 6 of the inside located at plasma separator 1 between entrance 4 and haemocyte outlet 5;
The upper end of oxygenator 2 is provided with oxygen/carbon dioxide entrance 7, and the inside of oxygenator 2 is provided with and oxygen/carbon dioxide The permeable fiber membrane tube 8 that entrance 7 is connected;
The side wall of reactor 3 is provided with thin with the nutrient solution of its inner space/hepatocyte suspension entrance 10 and nutrient solution/liver Born of the same parents' suspension outlet 11, the lower end of reactor 3 is provided with blood plasma/priming fluid outlet 12, intercommunicating pore 9 and blood plasma/priming fluid outlet 12 Connected with the hollow fiber film tube 13 of the inside located at reactor 3.
Wherein, the inlet end of device room connecting tube 25 is located at the side wall lower ends of plasma separator 1, and liquid outlet end is located at The lower end of oxygenator 2;Intercommunicating pore 9 is located at the upper end of oxygenator 2 and reactor 3.
The sealed support plate 19 for intercepting blood plasma/priming fluid is additionally provided with along its cross-sectional direction inside oxygenator 2, is sealed Supporting plate 19 is located at the top of intercommunicating pore 9;Multiple apertures, the upper end card of permeable fiber membrane tube 8 are offered on sealed support plate 19 It is located in aperture, and the space formed by sealed support plate 19 and the inner cavity top of oxygenator 2, with oxygen/carbon dioxide entrance 7 It is connected.
Inside plasma separator 1 two are additionally provided with for intercepting the polyurethane that cell and liquid pass through along its cross-sectional direction Resin scaffold plate 15, two polyurethane resin supporting plates 15 be located at respectively the upper and lower ends of plasma separator 1 and with plasma separator 1 End inner chamber is kept at a distance, and offers multiple through holes on polyurethane resin supporting plate 15, and the two ends of hollow fiber bundle 6 are blocked set respectively In the through hole of different polyurethane resin supporting plates 15, the inlet end of device room connecting tube 25 is located at two polyurethane resin supports Between plate 15.
Inside reactor 3 two are additionally provided with for intercepting the polyurethane resin that cell and liquid pass through along its cross-sectional direction Rack plate 16, two polyurethane resin rack plates 16 are located at respectively the upper and lower ends of reactor 3 and keep with the end inner chamber of reactor 3 Distance, offers multiple through holes on polyurethane resin rack plate 16, the two ends of hollow fiber film tube 13 are arranged in respectively different gathering In the through hole of urethane resin scaffold piece 16, intercommunicating pore 9 is located at the top of polyurethane resin rack plate 16, and nutrient solution/liver cell is hanged Supernatant liquid entrance 10 and nutrient solution/hepatocyte suspension outlet 11 are located between two polyurethane resin rack plates 16.
Plasma separator 1 is additionally provided with and the inner space of plasma separator 1 between two polyurethane resin supporting plates 15 The standby adding mouth 20 of plasma separator and plasma separator outlet 21;The lower end of oxygenator 2 is provided with oxygenator adding mouth 23;Device The inlet end of room connecting tube 25 connects with plasma separator outlet 21;The liquid outlet end of device room connecting tube 25 adds with oxygenator Sample mouth 23 is connected.
The upper end of oxygenator 2 is additionally provided with the sky of the standby adding mouth 22 of oxygenator, adding mouth 22 and the lower section of sealed support plate 19 Between be connected;The lower end of oxygenator 2 is provided with the adding mouth 14 for infusion medicine-feeding.
Permeable fiber membrane tube 8 is tortuous to be arranged, and shape can be helical form, snakelike shape or other curved shapes, its upper end with Oxygen/carbon dioxide entrance 7 is connected, and lower end is blind end.
Blood plasma/priming fluid outlet 12 is also provided with polyethersulfone filter film 18, polyethylene filter membrane or poly ethylene vinyl alcohol Filter membrane, its thickness is 100 μm ± 25 μm, and membrane aperture is 0.5 μm ± 0.1 μm.
The Micropump spare interface 24 for communicating therewith is additionally provided with oxygenator adding mouth 23.
When using, oxygen/carbon dioxide entrance 7 is first turned on, then opens blood/priming fluid entrance 4 and blood plasma/preliminary filling Liquid outlet 12, and by blood/saline injection of priming fluid entrance 4 with pre-flush bioreactor;Turn off blood/preliminary filling Liquid entrance 4, aseptically will inject reaction with liver cell microcarrier suspension from nutrient solution/hepatocyte suspension entrance 10 Device 3, the cavity for making whole reactor 3 is full of microcarrier cell suspension;Subsequently by the blood of acute hepatic failure pig model from blood/ Priming fluid entrance 4 introduces plasma separator 1, and after hollow fiber bundle 6, haemocyte and part blood plasma are exported blood from haemocyte 5 discharge, and remaining blood plasma enters the inner chamber of oxygenator 2 in the presence of pump 17 is separated by device room connecting tube 25, then by connection Hole 9 enters the inner chamber of reactor 3, and reactor 3 is discharged in last menses slurry/priming fluid outlet 12;The haemocyte that haemocyte outlet 5 is discharged The blood plasma discharged with blood plasma/priming fluid outlet 12 with part blood plasma is fed back in pig body after mixing, and is formed a treatment and is looped back Road.Over the course for the treatment of, to the inner chamber insufflation gas of oxygenator 2, gas is from permeable fiber membrane tube 8 for oxygen/carbon dioxide entrance 7 End is entered in permeable fiber membrane tube 8, because permeable fiber membrane tube 8 is placed in the inner chamber of oxygenator 2, so as to ensure certain dissolved oxygen, In the case of pH (carbon dioxide regulation), the circulation treatment of blood plasma can be maintained up to dozens of hour, terminate treatment, Kaplan-Meier survival analysises show that this treatment can significantly extend the time-to-live of animal subject.

Claims (10)

1. a kind of three-in-one type bioreactor of artificial liver, it is characterised in that:Including the plasma separator for being close to arrange side by side (1), oxygenator (2) and reactor (3);
The plasma separator (1) and the oxygenator (2) share side wall, and by device room connecting tube (25) from outside by two Person's inner space, device room connecting tube (25) is provided with separation pump (17);The reactor (3) shares another with the oxygenator (2) Side wall, and will both inner spaces by the intercommunicating pore (9) for opening up thereon;
The upper end of the plasma separator (1) is provided with blood/priming fluid entrance (4), and lower end is provided with haemocyte outlet (5);It is described Connected with the hollow fiber bundle (6) located at plasma separator (1) inside between blood/priming fluid entrance (4) and haemocyte outlet (5) It is logical;
The upper end of the oxygenator (2) is provided with oxygen/carbon dioxide entrance (7), and the inside of the oxygenator (2) is provided with and oxygen The permeable fiber membrane tube (8) that gas/carbon dioxide entrance (7) is connected;
The side wall of the reactor (3) be provided with the nutrient solution/hepatocyte suspension entrance (10) with its inner space and nutrient solution/ Hepatocyte suspension exports (11), and the lower end of the reactor (3) is provided with blood plasma/priming fluid outlet (12), the intercommunicating pore (9) Connected with the hollow fiber film tube (13) located at reactor (3) inside with blood plasma/priming fluid outlet (12).
2. three-in-one type bioreactor of artificial liver according to claim 1, it is characterised in that:Device room connecting tube (25) inlet end is located at the side wall lower ends of the plasma separator (1), and liquid outlet end is located under the oxygenator (2) End;The intercommunicating pore (9) is positioned at oxygenator (2) and the upper end of reactor (3).
3. three-in-one type bioreactor of artificial liver according to claim 2, it is characterised in that:In the oxygenator (2) Portion is additionally provided with the sealed support plate (19) for intercepting blood plasma/priming fluid, the sealed support plate (19) along its cross-sectional direction Positioned at the top of intercommunicating pore (9);Multiple apertures are offered on the sealed support plate (19), the permeable fiber membrane tube (8) Upper end is fastened in aperture, and the space formed by sealed support plate (19) and oxygenator (2) inner cavity top, with oxygen/bis- Carbonoxide entrance (7) is connected.
4. the three-in-one type bioreactor of artificial liver according to Claims 2 or 3, it is characterised in that:The blood plasma is separated Device (1) is internal to be additionally provided with two for intercepting the polyurethane resin supporting plate that cell and liquid pass through along its cross-sectional direction (15), two polyurethane resin supporting plates (15) are located at respectively plasma separator (1) upper and lower ends and hold with plasma separator (1) Portion's inner chamber is kept at a distance, and offers multiple through holes on the polyurethane resin supporting plate (15), and the two of the hollow fiber bundle (6) End is arranged in respectively in the through hole of different polyurethane resin supporting plates (15), and the inlet end of device room connecting tube (25) is located at Between two polyurethane resin supporting plates (15).
5. the three-in-one type bioreactor of artificial liver according to Claims 2 or 3, it is characterised in that:The reactor (3) It is internal to be additionally provided with two for intercepting the polyurethane resin rack plate (16) that cell and liquid pass through along its cross-sectional direction, two Polyurethane resin rack plate (16) is located at respectively reactor (3) upper and lower ends and keeps at a distance with reactor (3) end inner chamber, institute State and multiple through holes are offered on polyurethane resin rack plate (16), the two ends of the hollow fiber film tube (13) are arranged in respectively not In through hole with polyurethane resin rack plate (16), the intercommunicating pore (9) is positioned at the top of polyurethane resin rack plate (16), institute Nutrient solution/hepatocyte suspension entrance (10) and nutrient solution/hepatocyte suspension outlet (11) are stated positioned at two polyurethane resins Between rack plate (16).
6. three-in-one type bioreactor of artificial liver according to claim 4, it is characterised in that:The plasma separator (1) it is additionally provided between two polyurethane resin supporting plates (15) standby with the plasma separator of plasma separator (1) inner space With adding mouth (20) and plasma separator outlet (21);The lower end of the oxygenator (2) is provided with oxygenator adding mouth (23);Institute The inlet end for stating device room connecting tube (25) connects with the plasma separator outlet (21);Device room connecting tube (25) Liquid outlet end connects with the oxygenator adding mouth (23).
7. three-in-one type bioreactor of artificial liver according to claim 3, it is characterised in that:The oxygenator (2) Upper end is additionally provided with the standby adding mouth of oxygenator (22), and the adding mouth (22) is connected with the space below sealed support plate (19) It is logical;The lower end of the oxygenator (2) is provided with the adding mouth (14) for infusion medicine-feeding.
8. three-in-one type bioreactor of artificial liver according to claim 1, it is characterised in that:The permeable fiber membrane tube (8) tortuous to arrange, its upper end connects with the oxygen/carbon dioxide entrance (7), and lower end is blind end.
9. three-in-one type bioreactor of artificial liver according to claim 1, it is characterised in that:Blood plasma/the priming fluid Outlet (12) is provided with polyethersulfone filter film (18), polyethylene filter membrane or poly ethylene vinyl alcohol filter membrane, and its thickness is 100 μm ± 25 μm, membrane aperture is 0.5 μm ± 0.1 μm.
10. three-in-one type bioreactor of artificial liver according to claim 6, it is characterised in that:The oxygenator sample-adding The Micropump spare interface (24) for communicating therewith is additionally provided with mouth (23).
CN201620809802.1U 2016-07-29 2016-07-29 Trinity formula artificial liver bioreactor Expired - Fee Related CN206167482U (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201620809802.1U CN206167482U (en) 2016-07-29 2016-07-29 Trinity formula artificial liver bioreactor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201620809802.1U CN206167482U (en) 2016-07-29 2016-07-29 Trinity formula artificial liver bioreactor

Publications (1)

Publication Number Publication Date
CN206167482U true CN206167482U (en) 2017-05-17

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Application Number Title Priority Date Filing Date
CN201620809802.1U Expired - Fee Related CN206167482U (en) 2016-07-29 2016-07-29 Trinity formula artificial liver bioreactor

Country Status (1)

Country Link
CN (1) CN206167482U (en)

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Address after: 4th floor, podium building, Gongtou Building, No. 433-505 Chunhui Road, Lingxi Town, Cangnan County, Wenzhou City, Zhejiang Province, 325000

Patentee after: Zhejiang Tonggan Medical Technology Co.,Ltd.

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Address before: No. 818, Gaoxin Avenue, Donghu high tech Development Zone, Wuhan, Hubei 430206

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Granted publication date: 20170517

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