CN113181458A - Bioreactor for artificial liver - Google Patents
Bioreactor for artificial liver Download PDFInfo
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- CN113181458A CN113181458A CN202110433009.1A CN202110433009A CN113181458A CN 113181458 A CN113181458 A CN 113181458A CN 202110433009 A CN202110433009 A CN 202110433009A CN 113181458 A CN113181458 A CN 113181458A
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- 210000004185 liver Anatomy 0.000 title claims abstract description 64
- 210000004369 blood Anatomy 0.000 claims abstract description 113
- 239000008280 blood Substances 0.000 claims abstract description 113
- 239000012510 hollow fiber Substances 0.000 claims abstract description 93
- 239000011521 glass Substances 0.000 claims abstract description 44
- 235000015097 nutrients Nutrition 0.000 claims abstract description 39
- 239000012528 membrane Substances 0.000 claims abstract description 34
- 230000002093 peripheral effect Effects 0.000 claims abstract description 15
- 230000005684 electric field Effects 0.000 claims abstract description 13
- 230000007704 transition Effects 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 11
- 239000003822 epoxy resin Substances 0.000 claims description 9
- 229920000647 polyepoxide Polymers 0.000 claims description 9
- 238000007789 sealing Methods 0.000 claims description 6
- 239000011810 insulating material Substances 0.000 claims description 4
- 230000008676 import Effects 0.000 claims description 2
- 230000000149 penetrating effect Effects 0.000 claims description 2
- 239000003053 toxin Substances 0.000 abstract description 36
- 231100000765 toxin Toxicity 0.000 abstract description 36
- 108090000623 proteins and genes Proteins 0.000 abstract description 30
- 102000004169 proteins and genes Human genes 0.000 abstract description 30
- 230000005855 radiation Effects 0.000 abstract description 4
- 108700012359 toxins Proteins 0.000 description 35
- 230000000694 effects Effects 0.000 description 12
- 230000009471 action Effects 0.000 description 6
- 238000001784 detoxification Methods 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 230000005611 electricity Effects 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 3
- 235000017491 Bambusa tulda Nutrition 0.000 description 3
- 241001330002 Bambuseae Species 0.000 description 3
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 3
- 239000011425 bamboo Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
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- 239000007788 liquid Substances 0.000 description 3
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000005685 electric field effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
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- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003990 capacitor Substances 0.000 description 1
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- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
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- 238000001914 filtration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
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- 229910001414 potassium ion Inorganic materials 0.000 description 1
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Classifications
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- 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
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
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- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- External Artificial Organs (AREA)
Abstract
The invention discloses a bioreactor of an artificial liver, which comprises a round glass cylinder sealed by covers at two ends, wherein the center in the round cylinder is provided with a plurality of hollow fiber tubes made of hollow fiber membranes; the blood inlet pipe is communicated with one ends of all hollow fiber pipes, the blood outlet pipe is communicated with the other ends of all hollow fiber pipes, the nutrient solution inlet pipe and the nutrient solution outlet pipe are communicated with the peripheral gap, a plurality of first rod-type electrodes are fixed on the inner wall of the circular cylinder, a second rod-type electrode is fixed at the center of each hollow fiber pipe, one end of each first rod-type electrode is electrically connected with the negative electrode of the battery, one end of each second rod-type electrode is electrically connected with the positive electrode of the battery, the first rod-type electrodes are evenly distributed along the circumference of the inner wall of the circular glass cylinder, and a radial and uniform radiation electric field is formed between each first rod-type electrode and each second rod-type electrode. The bioreactor of the artificial liver can fully remove protein-bound toxin in blood and prolong the service life of the bioreactor of the artificial liver.
Description
Technical Field
The invention relates to the technical field of biomedical equipment, in particular to a bioreactor of an artificial liver.
Background
The artificial liver usually means that a mechanical device or a physicochemical device in vitro is used to drive the blood of a patient to flow through an in vitro artificial liver system by pressure, so as to take the function of temporarily assisting or completely replacing the seriously diseased liver, remove various harmful substances and compensate the metabolic function of the liver until the liver function of the human body is recovered or the liver is transplanted.
The bioreactor of the artificial liver is a component for removing toxins in the artificial liver system and is the core of the artificial liver system. The bioreactor of the artificial liver in the prior art comprises a circular cylinder sealed by covers at two ends, wherein a plurality of hollow fiber tubes made of hollow fiber membranes are arranged in the center of the circular cylinder, and the hollow fiber tubes and peripheral gaps outside the tubes form a place for radial substance exchange of blood and nutrient solution; the blood inlet pipe is communicated with one end of each hollow fiber pipe, the blood outlet pipe is communicated with the other end of each hollow fiber pipe, the nutrient solution inlet pipe and the nutrient solution outlet pipe are communicated with the peripheral gap,
the ideal artificial liver should be able to clear various toxins from the blood like the liver. However, only a small fraction of the toxins in the blood are water soluble, such as blood ammonia, and most of the toxins are water insoluble and bind to proteins, called protein-bound toxins, primarily to the negatively charged albumin that is present in the greatest amount in blood, such as plasma. The mechanism of liver failure is currently unclear, but it is widely accepted in the medical community that protein-bound toxins may be the major cause of liver failure. The existing artificial liver based on hemodialysis, filtration and other technologies can remove water-soluble toxins, but because the combination of protein-bound toxins and albumin is very tight, the removal of the protein-bound toxins is difficult. Moreover, the protein-bound toxins which are difficult to remove may be attached to the hollow fiber tube formed by the hollow fiber membrane of the bioreactor of the artificial liver, so that the protein-bound toxins are accumulated on the surface of the fiber tube wall, the mass transfer and detoxification effects of the hollow fiber tube are further influenced, the service life of the bioreactor of the artificial liver is also shortened, the bioreactor of the artificial liver needs to be replaced in time, and the medical cost is greatly increased. Therefore, technicians in the industry always set the length of the hollow fiber tube to be longer and the diameter of the hollow fiber tube to be smaller as much as possible, so that the contact area of blood and nutrient solution is larger, in order to improve the detoxification effect, and hope to prolong the service life of the bioreactor of the artificial liver. However, in the actual use process, the effect is not obvious, the protein-bound toxin still gathers and adsorbs on the surface of the hollow fiber membrane forming the hollow fiber tube, and the fine through holes of the fiber membrane part are blocked, and the fine small holes are blocked, so that the protein-bound toxin can not enter the peripheral gap outside the hollow fiber tube, namely the outer cavity, from the inner cavity, namely the hollow fiber tube, and the toxin-removing efficiency and the service life of the bioreactor of the artificial liver are influenced. How to improve the efficiency of removing protein-bound toxins by the artificial liver, realize efficient detoxification treatment of the artificial liver, and prolong the service life of a bioreactor of the artificial liver becomes a technical problem to be solved urgently in the technical field of the current artificial liver.
Disclosure of Invention
The invention aims to solve the technical problem of providing the bioreactor for the artificial liver, which can fully remove protein-bound toxin in blood and prolong the service life of the bioreactor for the artificial liver.
The invention provides a bioreactor of artificial liver, which comprises a round cylinder sealed by covers at two ends, wherein the center in the round cylinder is provided with a plurality of hollow fiber tubes made of hollow fiber membranes, and the hollow fiber tubes and peripheral gaps outside the tubes form a place for radial substance exchange of blood and nutrient solution; advance the one end of blood pipe intercommunication all hollow fiber pipes, go out the other end of blood pipe intercommunication all hollow fiber pipes, nutrient solution import pipe and nutrient solution outlet pipe intercommunication peripheral clearance, the lid is the insulating material preparation with a circular section of thick bamboo, be fixed with many first stick electrodes on the inner wall of a circular section of thick bamboo, the center of a plurality of hollow fiber pipes is fixed with at least one second stick electrode, the one end of first stick electrode is connected with the negative pole electricity of battery, the one end of second stick electrode is connected with the anodal electricity of battery, first stick electrode is along the inner wall circumference evenly distributed of a circular section of thick bamboo, form the electric field of radial evenly radiating between messenger's first stick electrode and the second stick electrode.
After adopting the structure, the bioreactor of the artificial liver has the following advantages: the invention departs from the conventional thinking that the contact area of the hollow fiber tube and the nutrient solution is increased to improve the detoxification effect in the prior art, and creatively provides the technical concept of generating a radial radiation electric field in the glass tube by using the rod type electrode under the action of the voltage of the battery to detoxify. The natural law of homopolar repulsion and heteropolar attraction is utilized: the positively charged toxin molecules in the blood in the central hollow fiber tube, namely protein-bound toxin, are accelerated to be separated from albumin in the blood under the action of an electric field, and are repelled by the central positive rod-type electrode and attracted by the plurality of negative rod-type electrodes on the wall of the circular glass tube, so that the protein-bound toxin rapidly and radially moves from the center to the circular tube, namely the wall of the circular glass tube, namely the protein-bound toxin and the protein are separated under the action of the radially and uniformly radiated electric field, and move from the tube, namely the inner cavity, of the hollow fiber tube to the peripheral gap outside the tube, namely the outer cavity, and the protein-bound toxin moving to the outer cavity flows out of the circular tube from the nutrient solution outlet along with the nutrient solution. The bioreactor of the artificial liver can fully remove protein-bound toxin in blood, and after a liver disease patient is treated by an artificial liver system adopting the bioreactor of the artificial liver, a treatment effect of efficiently detoxifying can be achieved. Meanwhile, the bioreactor of the artificial liver can always keep an excellent state of removing protein-bound toxin in blood, prevent the protein-bound toxin from being gathered in the hollow fiber membrane to block the fiber membrane hole, greatly prolong the service life of the bioreactor of the artificial liver, and become a technical problem which needs to be solved urgently in the technical field of the current artificial liver. Further influences the mass transfer detoxification effect of the hollow fiber tube, shortens the service life of the bioreactor of the artificial liver, needs to replace the biological reaction device of the artificial liver in time, and greatly reduces the medical cost of treating patients with liver diseases by adopting an artificial liver system.
Further, the round cylinder is a round glass cylinder; the second rod-type electrode is one; the two ends of the first rod-type electrode extend out of the two ends of the round glass cylinder, and the two ends of the second rod-type electrode extend out of the two ends of the round glass cylinder. After the structure is adopted, the environment of the material for radial material exchange of blood and nutrient solution is better, and the work is more stable and reliable; the coverage of the positive and negative rod type electrodes is wider, the electric field effect is more sufficient, and the technical effect of removing protein-bound toxin in blood is better.
Further, the first rod electrode and the second rod electrode are arranged in parallel with all the hollow fiber tubes. After adopting above structure, make the electric field effect more abundant, clear away the technical effect of albumen combination toxin in the blood better.
Furthermore, a plurality of radial arc-shaped grooves for embedding the first rod-type electrodes are formed in the inner wall of the circular glass cylinder, and the width dimension of gaps on the inner sides of the radial arc-shaped grooves is smaller than the diameter dimension of the first rod-type electrodes. After the structure is adopted, the adsorption effect of the first rod-shaped electrode, namely the negative electrode, is fully exerted, the first rod-shaped electrode is firmly fixed with the glass cylinder wall, and the operation is stable and reliable.
Further, the bioreactor of the artificial liver of the invention also comprises a disk-shaped blood inlet distributor; the covers at two ends are a first end cover and a transition end cover at one end and a second end cover at the other end; a blood inlet pipe on the disk-shaped blood inlet distributor penetrates through a central hole of the transition end cover and a central hole of the first end cover to extend outwards, and the blood inlet pipe is communicated with one end of each hollow fiber pipe through a plurality of channels in the disk-shaped blood inlet distributor and a plurality of first holes at the bottom end of the disk-shaped blood inlet distributor; the transition end cover is provided with a plurality of first through holes penetrating through one end of the first rod type electrode; the inner end face of the first end cover is provided with a plurality of first blind holes for accommodating one end of the first rod type electrode; the first end cover is provided with a battery box for accommodating a battery, the cathode of the battery is electrically connected with one end of each first rod-type electrode through a straight-line-shaped hard wire fixed on the inner end surface of the first end cover, a circular-ring-shaped hard wire with a notch and the ends of a plurality of radial hard wires, and the anode of the battery is electrically connected with one end of a second rod-type electrode positioned in the blood inlet pipe through an Contraband-shaped hard wire fixed on the inner side surface of the first end cover and a conductive structure arranged on the pipe wall of the blood inlet pipe. After the structure is adopted, the structure of the blood inlet pipe communicated with the hollow fiber pipes is simple and reasonable, and the connection structure of the battery and the first rod-type electrode and the second rod-type electrode is simple, reasonable, stable and reliable.
Furthermore, the circumference of each first hole of the disk-shaped blood inlet distributor is sealed with the circumference of one end of each hollow fiber tube in a one-to-one correspondence mode, the outer circumference of the bottom surface of the transition end cover is sealed with the top end surface of the circular glass cylinder, and the outer circumference of the bottom surface of the first end cover is sealed with the outer circumference of the top surface of the transition end cover. After adopting above structure, both guaranteed the smooth and easy intercommunication of entering blood liquid pipe and every hollow fiber pipe, made sealed reliable again.
Furthermore, the bioreactor of the artificial liver also comprises a disk-shaped blood outlet collector, a blood outlet pipe on the disk-shaped blood outlet collector extends outwards through the central hole of the second end cover, and the blood outlet pipe is communicated with the other ends of all the hollow fiber pipes through a plurality of channels in the disk-shaped blood outlet collector and a plurality of second holes at the top end of the disk-shaped blood outlet collector; the inner end face of the second end cover is provided with a plurality of second blind holes for accommodating the other end of the first rod type electrode. After the structure is adopted, the structure for communicating the blood liquid pipe with the plurality of hollow fiber pipes is simple and reasonable.
Furthermore, the circumference of each second hole of the disk-shaped blood outlet collector is sealed in one-to-one correspondence with the circumference of the other end of each hollow fiber tube, and the outer circumference of the top surface of the second end cover is sealed with the bottom end surface of the circular glass cylinder. After the structure is adopted, the smooth communication between the blood liquid pipe and the plurality of hollow fiber pipes is ensured, and the sealing is reliable.
Further, the diameter of the first rod electrode is smaller than the diameter of the second rod electrode. After the structure is adopted, the central positive rod type electrode has stronger function, stronger repulsive force to toxin molecules with positive electricity in blood, namely protein combined toxin, and stronger action of a radioactive electric field, and the speed of removing the protein combined toxin in the blood is quicker and more thorough.
Furthermore, the first rod-type electrode and the arc-shaped radial groove are fixed by conductive epoxy resin; two ends of the hollow fiber pipes are fixed into a cylindrical filter element consisting of a plurality of circles by adopting conductive epoxy resin; the sealing is realized by adopting conductive epoxy resin. After the structure is adopted, the adsorption effect of the first rod-type electrode, namely the negative electrode, is fully exerted, the smoothness of the blood channel and the nutrient solution channel is ensured, the fixing effect of the first rod-type electrode and the glass cylinder wall and the sealing effect among parts such as the end cover are better, and the work is more stable and reliable.
Drawings
FIG. 1 is a schematic perspective view of a bioreactor for artificial liver according to the present invention.
Fig. 2 is a schematic diagram one of the explosive structure of fig. 1.
Fig. 3 is a schematic diagram of the exploded structure of fig. 1.
Fig. 4 is a side bottom enlarged view of the first endcap of fig. 3.
Fig. 5 is a longitudinal sectional view of the structure of the present invention (schematic operation) with the end cap and the transition cap removed.
Fig. 6 is a front enlarged structural schematic view (schematic operation principle) of a single hollow fiber tube in fig. 5.
Fig. 7 is a longitudinal enlarged structural view of the hollow fiber membranes constituting the hollow fiber tubes in fig. 6 (i.e., a longitudinal enlarged structural view of one side tube wall).
Shown in the figure are 1, a blood inlet pipe, 2, a first end cap, 3, a round glass cylinder, 4, a second end cap, 5, a nutrient solution inlet pipe, 6, a nutrient solution outlet pipe, 7, a battery box, 8, a transition end cap, 9, a pie-shaped blood inlet distributor, 10, a radial arc-shaped groove, 11, a hollow fiber membrane, 12, a peripheral gap, 13, a pie-shaped blood outlet collector, 14, a second blind hole, 15, a second hole, 16, the other end of a first rod electrode, 17, one end of a second rod electrode, 18, one end of a hollow fiber pipe, 19, one end of a first rod electrode, 20, a first through hole, 21, a first blind hole, 22, the other end of a hollow fiber pipe, 23, the other end of a second rod electrode, 24, a blood outlet pipe, 25, a radial hard lead wire, 26, a first hole, 27, a positive electrode of a battery, 28, a battery, 29, a negative electrode of a battery, 30. contraband-shaped hard lead, 31, a terminal, 32, a circular hard lead, 33, a straight hard lead, 34, a notch, 35, a cylindrical filter element, 36, a second rod-type electrode, 37, a first rod-type electrode, 38, a conducting ring, 39, an elastic conducting sheet, 40, a conducting structure, 41 and a hollow fiber tube.
Detailed Description
The following further describes embodiments of the present invention with reference to the drawings. It is to be noted that the description of the embodiments is provided to aid understanding of the present invention, and is not intended to limit the present invention. In addition, the technical features involved in the respective embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
As shown in fig. 1, 2, 3, and 4.
The invention relates to a bioreactor of an artificial liver, which comprises a circular cylinder such as a circular glass cylinder 3 sealed by covers at two ends, wherein the center in the circular glass cylinder 3 is provided with a plurality of hollow fiber tubes 41 made of hollow fiber membranes 11, and the hollow fiber tubes 41 in the circular glass cylinder 3 and peripheral gaps 12 outside the tubes, namely the hollow fiber tubes 41, form a place for radial substance exchange of blood and nutrient solution. The blood inlet tube 1 is connected to one end 18 of all the hollow fiber tubes, the blood outlet tube 24 is connected to the other end 22 of all the hollow fiber tubes, and the nutrient solution inlet tube 5 and the nutrient solution outlet tube 6 are connected to the peripheral gap 12. The two covers are a first end cover 2 and a second end cover 4. The blood inlet tube 1 and the blood outlet tube 24 are both communicated with a blood delivery tube such as a hose and a pump of the artificial liver system for driving and delivery, and the nutrient solution inlet tube 5 and the nutrient solution outlet tube 6 are both communicated with a nutrient solution delivery tube such as a hose and a pump of the artificial liver system for driving and delivery (neither the above hose nor the pump is shown in the drawing). The above several roots may be understood as many roots, such as hundreds of roots, hundreds of dozens of roots (e.g. 100, 125 roots). The peripheral gap 12 is to be understood as all gaps outside all hollow fiber tubes within the circular glass cylinder 3 and the lid. The circular glass cylinder 3 is preferably a circular cylinder made of an insulating material such as plastic.
A plurality of first rod type electrodes 37 are fixed on the inner wall of the round glass cylinder 3, at least one, preferably one second rod type electrode 36 is fixed at the center of the plurality of hollow fiber tubes 41, one end 19 of the first rod type electrode is electrically connected with the negative electrode 29 of the battery, one end 17 of the second rod type electrode is electrically connected with the positive electrode 27 of the battery, the first rod type electrodes 37 are uniformly distributed along the circumference of the inner wall of the round glass cylinder 3, so that a radial uniform radiation electric field is formed between the first rod type electrodes 37 and the second rod type electrodes 36, namely the first rod type electrodes 37 and the second rod type electrodes 36 play a role similar to a capacitor, and the radial uniform radiation electric field is generated when the battery 28 is switched on. The diameter of the first rod electrode 37 is smaller than the diameter of the second rod electrode 36. The rod electrodes may also be referred to as pillar electrodes or rod electrodes, and the cross-section of the first rod electrode 37 and the cross-section of the second rod electrode 36 are both solid. More than one such as dozens, dozens (e.g., 16, 20, 24).
Both ends of the first rod electrode 37 extend out of both ends of the round glass cylinder 3, both ends of the second rod electrode 36 extend out of both ends of the round glass cylinder 3, i.e. one end 17 of the second rod electrode extends out of the upper end of the round glass cylinder 3, and the other end 23 of the second rod electrode extends out of the lower end of the round glass cylinder 3.
The first rod electrode 37 and the second rod electrode 36 are disposed in parallel with all the hollow fiber tubes 41.
The inner wall of the circular glass cylinder 3 is provided with a plurality of radial arc grooves 10 for embedding the first rod electrodes 37, and the width dimension of the gap at the inner side of the radial arc grooves 10 is smaller than the diameter dimension of the first rod electrodes 37.
The bioreactor for artificial liver of the present invention further comprises a disk-shaped blood inlet distributor 9. The two end covers are a first end cover 2 and a transition end cover 8 at one end and a second end cover 4 at the other end. The blood inlet pipe 1 of the disk-shaped blood inlet distributor 9 extends through the central hole of the transition end cap 8 and the central hole of the first end cap 2, and the blood inlet pipe 1 is communicated with one end 18 of all the hollow fiber tubes through a plurality of channels (not shown in the figure) in the disk-shaped blood inlet distributor 9 and a plurality of first holes 26 at the bottom end of the disk-shaped blood inlet distributor 9. The transition end cap 8 has a plurality of first through holes 20 through one end 19 of the first rod electrode, and the inner end surface of the first end 2 has a plurality of first blind holes 21 for receiving one end 19 of the first rod electrode. The first end cap 2 has a battery compartment 7 for receiving a battery 28, i.e. the battery 28 is mounted in the battery compartment 7. The negative electrode 29 of the battery is electrically connected with one end 19 of each first rod-shaped electrode through a straight-line-shaped hard lead 33 fixed on the inner end surface of the first end cover 2, a circular-ring-shaped hard lead 32 with a notch 34 and the end heads 31 of a plurality of radial hard leads 25, and the positive electrode 27 of the battery is electrically connected with one end 17 of the second rod-shaped electrode positioned in the blood inlet pipe 1 through an Contraband-shaped hard lead 30 fixed on the inner side surface of the first end cover 2 and a conductive structure 40 arranged on the pipe wall of the blood inlet pipe 1. The conductive structure 40 may be a specific structure of: the excircle root of the blood inlet pipe 1 is provided with a conductive ring 38 which is contacted with one end of the Contraband-shaped hard wire 30, and the conductive ring 38 is closely attached to one end 17 of the second rod-type electrode positioned in the blood inlet pipe 1 through an elastic conductive sheet 39 which penetrates through the pipe wall of the blood inlet pipe 1 and is sealed to conduct electricity. The nutrient solution inlet pipe 5 is arranged at the lower 1/3 position of the round glass cylinder 3, and the nutrient solution outlet pipe 6 is arranged at the upper 1/3 position of the round glass cylinder 3. One end 17 of the second rod electrode may be bent to facilitate electrical contact with the resilient conductive sheet 39.
The circumference of each first hole 26 of the disk-shaped blood inlet distributor 9 is sealed in one-to-one correspondence with the circumference of one end 18 of each hollow fiber tube, the outer circumference of the bottom surface of the transition end cap 8 is sealed with the top end surface of the circular glass cylinder 3, and the outer circumference of the bottom surface of the first end cap 2 is sealed with the outer circumference of the top surface of the transition end cap 8.
The bioreactor of the artificial liver further comprises a disk-shaped blood outlet collector 13, a blood outlet pipe 24 on the disk-shaped blood outlet collector 13 extends outwards through the central hole of the second end cover 4, and the blood outlet pipe 24 is communicated with the other ends 22 of all hollow fiber pipes through a plurality of channels in the disk-shaped blood outlet collector 13 and a plurality of second holes 15 at the top end of the disk-shaped blood outlet collector 13. The inner end face of the second end cap 4 has a plurality of second blind holes 14 for receiving the other end 23 of the first rod electrode. As shown in fig. 3, the first through holes 20 are not wide enough in the radial direction of the inner end surface of the transition end cover 8, and the portion of each first through hole 20 may be more than half of the hole. As shown in fig. 2, the second blind holes 14 are not wide enough in the radial direction of the inner end surface of the second end cap 4, and each second blind hole 14 may be partially a plurality of holes.
The circumference of each second hole 15 of the disk-shaped blood outlet collector 13 is sealed in one-to-one correspondence with the circumference of the other end 22 of each hollow fiber tube, and the outer circumference of the top surface of the second end cap 4 is sealed with the bottom end surface of the circular glass cylinder 3.
The first rod electrode 37 and the radial arc groove 10 are fixed by conductive epoxy resin. The two ends of the plurality of hollow fiber tubes 41 are fixed by conductive epoxy resin to form a cylindrical filter element 35 composed of a plurality of circles. The sealing, i.e. all the above sealing, is performed by conductive epoxy resin.
Bioreactors of artificial liver are also known as artificial liver hollow fiber modules. The round glass cylinder 3 is also called a round glass tube. The first end cap 2, the second end cap 4, the transition end cap 8, the pie-shaped blood inlet distributor 9, and the pie-shaped blood outlet collector 13 are all made of an insulating material such as plastic.
Blood is mainly composed of blood cells and plasma. In the treatment process of the artificial liver system, two forms are generally adopted, one is to directly introduce the blood of a patient into a bioreactor of the artificial liver for treatment, and the other is to separate blood cells from plasma and introduce the plasma into the bioreactor of the artificial liver for treatment. Blood is to be understood in the broad sense of the present invention, i.e. blood includes plasma. While nutrient solutions such as potassium ion solution and sodium ion solution have the function of maintaining the osmotic pressure of blood, and glucose can provide nutrient substances.
As shown in fig. 1, fig. 2, fig. 3, fig. 4, fig. 5, and fig. 6, the blood with protein-bound toxin enters each hollow fiber tube of the cylindrical filter element 35 composed of a plurality of hollow fiber tubes 41 located at the center of the circular glass cylinder 3 from the blood inlet tube 1 through the disk-shaped blood inlet distributor 9, each hollow fiber tube can be referred to as an inner cavity, and then each hollow fiber tube 41 flows out from the blood outlet tube 24 through the disk-shaped blood outlet collector 13. The nutrient solution or dialysate or culture solution flows into the peripheral gap 12 outside each hollow fiber tube from the nutrient solution inlet tube 5 on the side wall of the round glass cylinder 3, the peripheral gap 12 can be called outer cavity, and the nutrient solution flows out from the nutrient solution outlet tube 6 on the side wall of the round glass cylinder 3. Positively charged toxin molecules in blood in the central hollow fiber tube, namely protein-bound toxin, are accelerated to be separated from albumin in the blood under the action of an electric field, and are repelled by the central second rod-shaped electrode 36, namely a positive rod-shaped electrode, and attracted by the plurality of first rod-shaped electrodes 37, namely negative rod-shaped electrodes, on the wall of the circular glass tube 3, so that the protein-bound toxin moves from the center to the wall of the circular glass tube 3 in a rapid radial shape, namely the protein-bound toxin is separated from protein under the action of a radial uniformly radiated electric field and moves from the inner cavity of the hollow fiber tube 41 to the outer cavity, the protein-bound toxin moving to the outer cavity flows out of the circular glass tube 3 from the nutrient solution outlet pipe 6 along with the nutrient solution, the blood and the nutrient solution exchange substances through the hollow fiber membrane 11 in the radial direction, and meanwhile, the nutrient solution can supplement some missing beneficial substances to the blood through the hollow fiber membrane 11, that is, the blood flowing out of the blood outflow tube 24 is sterilized and supplemented with the beneficial agent. The hollow fiber membrane 11 used in the artificial liver is commonly used different membrane materials such as polyethersulfone membrane, polysulfone membrane, cellulose acetate membrane, polypropylene membrane, mixed cellulose ester membrane, etc., and the hollow fiber membrane 11 is a porous membrane, is a selective permeable membrane, has a certain molecular weight cut-off range, and has a structure as shown in a schematic diagram of fig. 7. Fig. 7 is an enlarged schematic view of the longitudinal sectional structure of the hollow fiber membranes 11 constituting each hollow fiber tube 41, and it can be helpful to us to further understand the above working principle with reference to fig. 7, which corresponds to a cut in the thickness direction of the hollow fiber membranes 11, looking at the internal structure of the hollow fiber membranes 11: contains fine through holes, molecules can pass through, and an electric field can pass through (i.e. from the electrical point of view, the fiber membrane is not insulated, but can penetrate the electric field), that is, the hollow fiber membrane 11 constituting the hollow fiber tube 41 is a selective permeable membrane, the white circles, the triangles and the black circles in the figure respectively represent molecules with different sizes, wherein small black spots such as protein-bound toxin molecules and oxygen molecules in blood can pass through the fine through holes from the inside to the outside and can pass through the hollow fiber membranes 11, wherein small black spots such as molecules of nutrient solution supplementing some beneficial substances missing in blood can pass through the fine through holes from outside to inside and can pass through the hollow fiber membrane 11, while the empty circles and triangles are such as other larger molecular substances in blood and other larger molecular substances in nutrient solutions such as cannot cross the fibrous membrane. FIG. 7 is taken on page 47 of a textbook entitled "basic principles of Membrane technology", published in 7 months 1997: edition 2, Marcel Mulder, lie.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and it will be apparent to those skilled in the art that various modifications and variations of the present invention are possible, such as changing the shape of the electrode, changing the rod type electrode to a plate type electrode having a rectangular cross section. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A bioreactor of artificial liver comprises a circular cylinder sealed by covers at two ends, a plurality of hollow fiber tubes made of hollow fiber membranes are arranged in the center of the circular cylinder, and the hollow fiber tubes and peripheral gaps outside the tubes form a place for radial substance exchange of blood and nutrient solution; advance the one end of all hollow fiber pipes of blood pipe intercommunication, go out the other end of all hollow fiber pipes of blood pipe intercommunication, nutrient solution import pipe and nutrient solution outlet pipe intercommunication peripheral clearance, its characterized in that: the cover and the round tube are made of insulating materials, a plurality of first rod-type electrodes are fixed on the inner wall of the round tube, at least one second rod-type electrode is fixed at the center of each hollow fiber tube, one end of each first rod-type electrode is electrically connected with the negative electrode of the battery, one end of each second rod-type electrode is electrically connected with the positive electrode of the battery, and the first rod-type electrodes are uniformly distributed along the circumference of the inner wall of the round tube, so that a radial uniformly-radiating electric field is formed between each first rod-type electrode and each second rod-type electrode.
2. The bioreactor of artificial liver according to claim 1, characterized in that: the round cylinder is a round glass cylinder; the second rod-type electrode is one; the two ends of the first rod-type electrode extend out of the two ends of the round glass cylinder, and the two ends of the second rod-type electrode extend out of the two ends of the round glass cylinder.
3. The bioreactor of artificial liver according to claim 2, characterized in that: the first rod electrode, the second rod electrode and all the hollow fiber tubes are arranged in parallel.
4. The bioreactor of artificial liver according to claim 3, characterized in that: the inner wall of the round glass cylinder is provided with a plurality of radial arc grooves for embedding the first rod type electrodes, and the width size of gaps on the inner sides of the radial arc grooves is smaller than the diameter size of the first rod type electrodes.
5. The bioreactor of artificial liver according to claim 4, characterized in that: also includes a pie-shaped blood inlet distributor; the covers at two ends are a first end cover and a transition end cover at one end and a second end cover at the other end; a blood inlet pipe on the disk-shaped blood inlet distributor penetrates through a central hole of the transition end cover and a central hole of the first end cover to extend outwards, and the blood inlet pipe is communicated with one end of each hollow fiber pipe through a plurality of channels in the disk-shaped blood inlet distributor and a plurality of first holes at the bottom end of the disk-shaped blood inlet distributor; the transition end cover is provided with a plurality of first through holes penetrating through one end of the first rod type electrode; the inner end face of the first end cover is provided with a plurality of first blind holes for accommodating one end of the first rod type electrode; the first end cover is provided with a battery box for accommodating a battery, the cathode of the battery is electrically connected with one end of each first rod-type electrode through a straight-line-shaped hard wire fixed on the inner end surface of the first end cover, a circular-ring-shaped hard wire with a notch and the ends of a plurality of radial hard wires, and the anode of the battery is electrically connected with one end of a second rod-type electrode positioned in the blood inlet pipe through an Contraband-shaped hard wire fixed on the inner side surface of the first end cover and a conductive structure arranged on the pipe wall of the blood inlet pipe.
6. The bioreactor of artificial liver according to claim 5, characterized in that: the circumference of each first hole of the disk-shaped blood inlet distributor is sealed with the circumference of one end of each hollow fiber tube in a one-to-one correspondence mode, the outer circumference of the bottom surface of the transition end cover is sealed with the top end face of the circular glass cylinder, and the outer circumference of the bottom surface of the first end cover is sealed with the outer circumference of the top surface of the transition end cover.
7. The bioreactor of artificial liver according to claim 5, characterized in that: the blood outlet pipe on the round cake-shaped blood outlet collector extends outwards through the central hole of the second end cover and is communicated with the other ends of all the hollow fiber pipes through a plurality of channels in the round cake-shaped blood outlet collector and a plurality of second holes at the top end of the round cake-shaped blood outlet collector; the inner end face of the second end cover is provided with a plurality of second blind holes for accommodating the other end of the first rod type electrode.
8. The bioreactor of artificial liver according to claim 7, characterized in that: the circumference of each second hole of the disk-shaped blood outlet collector is sealed in one-to-one correspondence with the circumference of the other end of each hollow fiber tube, and the outer circumference of the top surface of the second end cover is sealed with the bottom end surface of the circular glass cylinder.
9. The bioreactor of artificial liver according to claim 1, characterized in that: the diameter of the first rod electrode is smaller than the diameter of the second rod electrode.
10. Bioreactor of an artificial liver according to claim 6 or 8, characterized in that: the first rod-type electrode and the arc-shaped radial groove are fixed by conductive epoxy resin; two ends of the hollow fiber pipes are fixed into a cylindrical filter element consisting of a plurality of circles by adopting conductive epoxy resin; the sealing is realized by adopting conductive epoxy resin.
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| CN202110433009.1A CN113181458A (en) | 2021-04-22 | 2021-04-22 | Bioreactor for artificial liver |
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| CN202110433009.1A CN113181458A (en) | 2021-04-22 | 2021-04-22 | Bioreactor for artificial liver |
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Application publication date: 20210730 |