CN111909829A

CN111909829A - Perfusion type bioreactor for bioartificial liver

Info

Publication number: CN111909829A
Application number: CN202010946019.0A
Authority: CN
Inventors: 张文健; 娄晋宁
Original assignee: Suzhou Rui Lai Biotechnology Co ltd
Current assignee: Suzhou Rui Lai Biotechnology Co ltd
Priority date: 2020-09-11
Filing date: 2020-09-11
Publication date: 2020-11-10

Abstract

The invention provides a perfusion bioreactor for a bioartificial liver, which is characterized by comprising a cylindrical shell, a plasma inlet and a sealing cover at the lower end of the shell, a plasma outlet and a sealing cover at the upper end of the shell, a cell filling port and a sealing cover at the side surface, and an upper filter screen and a lower filter screen which are arranged in the reactor and are close to the centers of two ends and protrude outwards. The perfusion bioreactor for the bioartificial liver has the advantages that: 1. an independent cell filling port is arranged, so that cells can be conveniently filled into the reactor; 2. the center of the filter screen at the plasma inlet side in the reactor protrudes towards the plasma inlet side, so that the plasma is favorably dispersed after entering the reactor; 3. the center of the filter screen at the plasma outlet side in the reactor is raised towards the plasma outlet side, so that the discharge of bubbles during pre-flushing is facilitated; 4. the internal structure is simple, sufficient space is provided for the sufficient contact of cells and blood plasma, and the material exchange is facilitated, so that the function of the bioartificial liver reactor is effectively exerted.

Description

Perfusion type bioreactor for bioartificial liver

Technical Field

The invention belongs to the field of biology, and particularly relates to a perfusion bioreactor for a bioartificial liver.

Background

The most effective treatment for liver disease in the world today is liver transplantation, but the shortage of liver donors makes patients wait for liver source, and some patients eventually die because of waiting for liver source. Thus, artificial liver support systems have emerged as "bridges" that allow patients to wait for liver transplantation or their own liver to recover.

The artificial liver system (non-biological artificial liver) in the traditional sense can physically reduce the plasma toxins in a short time through hemodialysis, plasmapheresis, activated carbon adsorption and other measures, but does not have the normal functions of detoxification, metabolism and secretion of the liver. The development of bioartificial liver support systems using hepatocytes cultured in vitro has become an important issue because active human hepatocytes are used in vitro to replace the liver of a patient for detoxification, metabolism, and secretion functions, thereby reducing the burden on the liver of the patient and allowing the liver to recover by itself.

The structural part of the bioartificial liver containing hepatocytes is the site where hepatocytes exert the functions of detoxification, metabolism, and secretion, and is called a bioreactor. At present, the bioreactors of the conventional bioartificial liver support system mainly include hollow fiber bioreactors, plate bioreactors, and perfusion bioreactors. Wherein, the hollow fiber reactor has good safety, but the plasma and the cells are separated by a semipermeable membrane, which is not beneficial to material exchange and detoxification, thereby having poor treatment effect; if the plate bioreactor needs to reach the effective cell number, the number of layers of culture plates needs to be increased continuously, although the plate bioreactor is easy to enlarge, the volume of the plate bioreactor is increased at the same time, and the plate bioreactor is not beneficial to use; the plasma in the perfusion bioreactor is directly contacted with the liver cells, so that the physiological function of the perfusion bioreactor can be more easily exerted.

Generally, when clinical needs exist, a perfusion bioreactor for the bioartificial liver fills hepatic cell suspension or microcarrier suspension with hepatic cells into the bioreactor, and then starts to be used after pre-washing and removing air bubbles. In order to maintain the activity and functions of cells in the perfusion bioreactor of the bioartificial liver, the structure of the perfusion bioreactor is convenient to operate, and the short time consumption of cell filling, pre-flushing and bubble discharging is ensured.

Disclosure of Invention

Aiming at the functional requirements of the perfusion bioreactor for the bioartificial liver, the invention aims to provide the perfusion bioreactor for the bioartificial liver.

In order to achieve the purpose, the invention adopts the following design scheme: comprises a cylindrical shell 1, a plasma inlet 2 and a sealing cover 3 at the lower end of the shell, a plasma outlet 4 and a sealing cover 5 at the upper end of the shell, a cell filling opening 6 and a sealing cover 7 at the side surface, a filter screen 8 close to the plasma inlet side in the reactor and a filter screen 9 close to the plasma outlet side in the reactor.

In the perfusion bioreactor for the bioartificial liver, the cell filling port 6 on the side surface is positioned between the filter screen 8 and the filter screen 9, namely the cell filling port is communicated with the inside of the perfusion bioreactor. When filling cells, the sealing cover 7 and the sealing cover 5 are opened and respectively connected with pipelines, cell suspension is filled into the perfusion bioreactor from the cell filling opening 6, redundant liquid flows out from the plasma outlet 4, and the sealing cover 5 and the sealing cover 7 are covered after filling is finished.

The center of the filter screen 8 and the center of the filter screen 9 of the biological artificial liver perfusion bioreactor are both convex towards the outside.

The biological artificial liver perfusion bioreactor, wherein the purpose of the filter screen 8 and the filter screen 9 is to intercept the microcarrier and prevent the microcarrier from leaking out of the reactor. The diameter of the commonly used microcarrier is 50-300 μm, therefore, the aperture of the filter screen 8 and the filter screen 9 in the perfusion bioreactor of the invention is 25-300 μm, preferably 50-200 μm, and more preferably 100-150 μm.

The biological artificial liver perfusion bioreactor is characterized in that the filter screen is made of medical materials including but not limited to alloy, polytetrafluoroethylene, terylene and nylon. Wherein the alloy has better hardness, when the alloy is used for a filter screen close to the plasma inlet end in the reactor, the center convex shape can be kept, and if other softer mesh fabrics are used, an alloy or medical plastic support strip is added on the filter screen.

In the biological artificial liver perfusion bioreactor, the materials except the filter screen are all medical plastics.

The invention has the advantages that:

1. an independent cell filling port is arranged, so that cells can be conveniently filled into the reactor;

2. the center of the filter screen at the plasma inlet side in the reactor protrudes towards the plasma inlet side, so that the plasma is favorably dispersed after entering the reactor;

3. the center of the filter screen at the plasma outlet side in the reactor is raised towards the plasma outlet side, so that the discharge of bubbles during pre-flushing is facilitated;

4. the internal structure is simple, sufficient space is provided for the sufficient contact of cells and blood plasma, and the material exchange is facilitated, so that the function of the bioartificial liver is effectively exerted.

Drawings

FIG. 1: the structure schematic diagram of the perfusion bioreactor for the bioartificial liver.

FIG. 2: screen support schematic.

Reference numerals: 1: a housing; 2: a plasma inlet; 3: a plasma inlet sealing cover; 4: a plasma outlet; 5: a plasma outlet sealing cover; 6: a cell filling port; 7: sealing the cell filling opening; 8: a plasma inlet side filter screen; 9: a plasma outlet side filter screen; 10: a filter screen bracket.

Detailed Description

To further explain the technical means and effects of the present invention for achieving the intended purpose, the present invention will be further described in detail with reference to the accompanying drawings in combination with the embodiments. It is to be understood that this description is made only by way of example and not as a limitation on the scope of the invention. Further, in the following description, descriptions of structures and techniques known to those skilled in the art are omitted.

As shown in fig. 1, the perfusion bioreactor for bioartificial liver of the present invention comprises a cylindrical housing 1, a plasma inlet 2 and a sealing cap 3 at the lower end of the housing, a plasma outlet 4 and a sealing cap 5 at the upper end of the housing, a cell filling port 6 and a sealing cap 7 at the side, a filter screen 8 at the side close to the plasma inlet side inside the reactor, and a filter screen 9 at the side close to the plasma outlet side inside the reactor.

In the embodiment, the filter screen 8 and the filter screen 9 are made of nylon materials, the filter screen support 10 shown in fig. 2 is arranged on the filter screen, the filter screen support, the cylindrical shell and the sealing cover are made of medical plastics, and the edge of the filter screen support and the cylindrical shell are sealed into a whole.

When the biological artificial liver perfusion bioreactor is used, the plasma outlet end of the biological artificial liver perfusion bioreactor is upward, the sealing cover of the plasma outlet is opened, the plasma outlet is connected with a waste liquid bottle through a medical silica gel tube, then the sealing cover of the cell filling port is opened, the cell filling port is connected with a liquid storage bottle filled with microcarrier cell suspension through the medical silica gel tube, then the microcarrier cell suspension is filled into the reactor from bottom to top by using a peristaltic pump, and redundant liquid is discharged into the waste liquid bottle from the plasma outlet end.

The invention has been described above with reference to a preferred embodiment, but the scope of protection of the invention is not limited thereto, and various modifications can be made and equivalents can be substituted for elements thereof without departing from the scope of the invention, so long as there is no structural conflict, the technical features mentioned in the embodiment can be combined in any way, and any reference sign in the claims should not be construed as limiting the claim concerned. Therefore, all technical solutions that fall within the scope of the claims are within the scope of the present invention.

There is shown in the drawings, which are not to scale, a schematic structural view of a cross-section of the invention, wherein certain details are exaggerated and some details that may be readily conceived are omitted for clarity of description of certain structures. The shapes of various regions, details, and relative sizes and positional relationships therebetween shown in the drawings are merely examples, and may be slightly deviated due to production errors or technical limitations in actual manufacturing, and a person skilled in the art may additionally design regions having different shapes, sizes, relative positions according to actual needs.

Claims

1. The utility model provides a biological artificial liver perfusion bioreactor which characterized in that includes cylindrical shell (1), plasma entry (2) and sealed lid (3) of shell lower extreme, plasma export (4) and sealed lid (5) of shell upper end, cell filling mouth (6) and sealed lid (7) of side, inside filter screen (8) and the inside filter screen (9) that are close to the plasma outlet side of reactor that are close to the plasma inlet side of reactor.

2. A bioartificial liver perfusion bioreactor as claimed in claim 1, wherein the side cell filling port (6) is located between the strainer (8) and the strainer (9).

3. A bioartificial liver perfusion bioreactor as claimed in claim 1, wherein the centers of the filter net (8) and the filter net (9) are convex towards the outside.

4. A bioartificial liver perfusion bioreactor as claimed in claim 1, wherein the pore size of the filter mesh (8) and the filter mesh (9) is 25-300 μm, preferably 50-200 μm, more preferably 100-150 μm.

5. The perfusion bioreactor of claim 1, wherein the filter screens (8, 9) are made of medical materials including but not limited to alloy, teflon, dacron, nylon.

6. The perfusion bioreactor for the bioartificial liver as claimed in claim 1, wherein when the filter net (8) and the filter net (9) are made of soft mesh cloth, the filter net is provided with a filter net bracket (10) made of alloy or medical plastic.

7. The perfusion bioreactor for the bioartificial liver as claimed in claim 1, wherein the materials except the filter screen are medical plastics.